{ "$schema_version": "5.3", "review_mode": "fresh", "claim_restatement": { "index_wording": "HIV as the Cause of AIDS", "entry_form": "claim", "gradeable_restatement": "HIV infection is the necessary cause of AIDS.", "restatement_required": true, "split_into": [], "parent_claim": null, "scope_qualifiers": [ { "qualifier": "Clinical HIV infection and HIV-associated AIDS; other acquired immune deficiencies kept separate", "determinable_before_outcome": true, "determined_from": "Enrollment and experimental design, before results; no responder-defined scope.", "action": "retained" } ] }, "hypothesis": { "name": "HIV as the Cause of AIDS", "central_claim": "HIV infection is the necessary cause of AIDS.", "proposed_mechanism": "HIV infection is the necessary cause of AIDS.", "claimed_scope": "Clinical HIV-associated AIDS as a viral causal syndrome, rather than every possible acquired CD4-deficiency or opportunistic-infection phenotype", "claimed_level": [ "initiation", "progression", "necessity" ], "is_conjunctive": true, "conjunctive_note": "SC3 is the clinical causal claim at the registered scope; narrower molecular, treatment or inherited-syndrome findings cannot replace it. Primary-subclaim aggregation is fixed before grading." }, "rubric_routing": { "primary_rubric": "05-immunology-inflammation.md", "secondary_rubrics": [], "index_notes_applied": [ "SC3 is the clinical causal claim at the registered scope; narrower molecular, treatment or inherited-syndrome findings cannot replace it. Primary-subclaim aggregation is fixed before grading." ], "rubric_fit_note": "05-immunology-inflammation is the closest rubric to acquired immunodeficiency, but the causal target is a virus rather than an upstream cytokine. Its targeted-human-therapy and natural-experiment definitions are applied to viral suppression and clinical disease trajectories. This explicit scope-fit adaptation retains clinical endpoints and target alignment; inflammatory-marker changes do not cross thresholds. The universal distinction between necessity and sufficiency governs the nominal claim." }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "HIV acquisition precedes characteristic progressive CD4 depletion and AIDS outcomes in longitudinal human cohorts.", "subclaim_type": "mechanism", "scope": "Acquired HIV-associated immunodeficiency, distinguished from other immunodeficiencies", "claimed_scope": "Acquired HIV-associated immunodeficiency, distinguished from other immunodeficiencies", "governing_rubric": "05-immunology-inflammation.md", "key_evidence_anchor": "Prospective seroconversion and documented exposure cohorts", "hsef_level": "Η", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Documented seroconversion precedes immune deterioration across clinical exposure settings. This observational chain is interpreted together with randomized viral suppression and clinical rescue; it is not made causal by prognostic RNA correlations alone." }, { "id": "SC2", "statement": "Suppressing HIV causally prevents or reverses characteristic immunodeficiency and reduces AIDS events.", "subclaim_type": "necessity", "scope": "Clinical HIV infection, intervention timing and viral engagement specified", "claimed_scope": "Clinical HIV infection, intervention timing and viral engagement specified", "governing_rubric": "05-immunology-inflammation.md", "key_evidence_anchor": "Randomized antiviral suppression, interruption and early-treatment trials", "hsef_level": "Θ", "confidence": "High", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Earlier sustained ART improves CD4 and clinical outcomes, while interruption harms selected populations. Broad predictive consistency survives known timing and toxicity limits. Clinical suppression benefit is not infection-alone sufficiency." }, { "id": "SC3", "statement": "HIV infection is the necessary causal antecedent of AIDS, independently of definitional classification.", "subclaim_type": "necessity", "scope": "AIDS pathophysiology attributable to HIV; not every syndrome of low CD4 counts", "claimed_scope": "AIDS pathophysiology attributable to HIV; not every syndrome of low CD4 counts", "governing_rubric": "05-immunology-inflammation.md", "key_evidence_anchor": "Convergent temporality, exposure, host-resistance and intervention evidence", "hsef_level": "Θ", "confidence": "High", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "HIV is a necessary causal antecedent of the HIV-associated AIDS process under the registered clinical distinction, supported by convergent acquisition, temporality and suppression evidence rather than classification alone. Generic immunodeficiency has other causes. Host controllers and treatment change progression without removing the viral antecedent. Necessity does not imply inevitable AIDS." } ], "aggregation_rule": "primary-subclaim", "aggregation_preregistered": true, "aggregation_rationale": "SC3 is the clinical causal claim at the registered scope; narrower molecular, treatment or inherited-syndrome findings cannot replace it. Primary-subclaim aggregation is fixed before grading.", "primary_subclaim_id": "SC3", "aggregation_derivation": "Overall Θ follows registered SC3. The convergent clinical causal case is strong and predictively consistent: documented acquisition precedes immune deterioration, suppression changes clinical trajectories, interrupted suppression worsens them, and prophylaxis prevents acquisition. Host and coinfection modifiers make infection insufficient for inevitable disease. Non-HIV ICL shows that low CD4/OI phenotypes are not HIV-specific; its existence does not erase the viral causal process established by intervention, but it blocks a broader claim that HIV is necessary for all acquired immunodeficiency.", "aggregation_alternatives": { "weakest_link_would_return": "Η", "primary_subclaim_would_return": "Θ", "scope_matched_would_return": "Θ", "note": "Separate narrow successes do not replace the preregistered gate." }, "index_rule_deviation": "" }, "competing_models": { "models_evaluated": [ { "rank_in_tournament": 1, "model_id": "M1", "is_nominal": true, "name": "HIV-driven acquired immunodeficiency", "core_claim": "Persistent HIV infection drives a modifiable immune-deficiency trajectory.", "explains_what_nominal_does_not": "Persistent HIV infection drives a modifiable immune-deficiency trajectory.", "strongest_supporting_evidence": [ "Prospective acquisition and randomized suppression, interruption and prevention findings converge." ], "strongest_contradictory_evidence": [ "Host controllers, residual disease and treatment timing preclude infection-alone sufficiency." ], "hsef_level_for_this_model": "Θ", "rationale": "Prospective acquisition and randomized suppression, interruption and prevention findings converge. Host controllers, residual disease and treatment timing preclude infection-alone sufficiency." }, { "rank_in_tournament": 2, "model_id": "M2", "is_nominal": false, "name": "HIV with host and coinfection modifiers", "core_claim": "Host factors and concurrent diseases modify a viral causal trajectory.", "explains_what_nominal_does_not": "Host factors and concurrent diseases modify a viral causal trajectory.", "strongest_supporting_evidence": [ "Genetic, age and coinfection findings and timing trials explain meaningful heterogeneity." ], "strongest_contradictory_evidence": [ "This is compatible with the nominal viral antecedent; the full set of proposed modifier mechanisms is not selectively proven." ], "hsef_level_for_this_model": "Γ", "rationale": "Genetic, age and coinfection findings and timing trials explain meaningful heterogeneity. This is compatible with the nominal viral antecedent; the full set of proposed modifier mechanisms is not selectively proven." }, { "rank_in_tournament": 3, "model_id": "M3", "is_nominal": false, "name": "Non-HIV immunodeficiency phenocopies", "core_claim": "Other conditions produce low CD4 counts and opportunistic disease.", "explains_what_nominal_does_not": "Other conditions produce low CD4 counts and opportunistic disease.", "strongest_supporting_evidence": [ "ICL cohorts document non-HIV clinical lookalikes." ], "strongest_contradictory_evidence": [ "They do not explain HIV-linked acquisition and randomized viral-suppression effects or identify a universal alternative cause." ], "hsef_level_for_this_model": "Β", "rationale": "ICL cohorts document non-HIV clinical lookalikes. They do not explain HIV-linked acquisition and randomized viral-suppression effects or identify a universal alternative cause." }, { "rank_in_tournament": 4, "model_id": "M4", "is_nominal": false, "name": "Nonviral exposure or behavioral confounding", "core_claim": "HIV measurements merely mark another exposure causing the syndrome.", "explains_what_nominal_does_not": "HIV measurements merely mark another exposure causing the syndrome.", "strongest_supporting_evidence": [ "Exposure and historical observational cohorts alone could be confounded." ], "strongest_contradictory_evidence": [ "Specific acquisition prevention, infant progression benefit and randomized suppression/interruption are poorly explained by confounding alone." ], "hsef_level_for_this_model": "Α", "rationale": "Exposure and historical observational cohorts alone could be confounded. Specific acquisition prevention, infant progression benefit and randomized suppression/interruption are poorly explained by confounding alone." } ], "tournament_summary": "Descriptive comparison; does not modify the nominal score. The strongest causal separation is randomized virus-directed suppression with measured viral/CD4 change and independently adjudicated clinical endpoints, complemented by prevention of acquisition. Compatible modifiers are not competing denials and are not ranked as a fully proven causal bundle.", "study_separating_rank1_from_rank2": "The strongest causal separation is randomized virus-directed suppression with measured viral/CD4 change and independently adjudicated clinical endpoints, complemented by prevention of acquisition. Compatible modifiers are not competing denials and are not ranked as a fully proven causal bundle.", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true }, "evidence_inventory": [ { "n": 1, "pmid": "12487823", "title": "Rapid disease progression in human immunodeficiency virus type 1-infected seroconverters in India.", "citation": "Mehendale SM, Bollinger RC, Kulkarni SS et al. Rapid disease progression in human immunodeficiency virus type 1-infected seroconverters in India. AIDS research and human retroviruses. 2002.", "doi": "10.1089/08892220260387913", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/12487823/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/12487823/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID12487823", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Documented seroconversion precedes increasing viral load and CD4 decline in 46 untreated Indian participants.", "what_it_does_not_show": "Two-year small cohort does not alone isolate HIV from host and setting modifiers.", "confounders_present": [ "Two-year small cohort does not alone isolate HIV from host and setting modifiers." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 2, "pmid": "9875579", "title": "Evaluation of guidelines for initiation of highly active antiretroviral therapy in a longitudinal cohort of HIV-infected individuals.", "citation": "Ioannidis JP, O'Brien TR, Goedert JJ. Evaluation of guidelines for initiation of highly active antiretroviral therapy in a longitudinal cohort of HIV-infected individuals. AIDS (London, England). 1998.", "doi": "10.1097/00002030-199818000-00010", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/9875579/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/9875579/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID9875579", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Historical untreated progression differs across candidate ART-initiation criteria.", "what_it_does_not_show": "Prediction of historical progression is not a randomized comparison of the recommended thresholds.", "confounders_present": [ "Prediction of historical progression is not a randomized comparison of the recommended thresholds." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 3, "pmid": "18648514", "title": "Abundance of early functional HIV-specific CD8+ T cells does not predict AIDS-free survival time.", "citation": "Schellens IM, Borghans JA, Jansen CA et al. Abundance of early functional HIV-specific CD8+ T cells does not predict AIDS-free survival time. PloS one. 2008.", "doi": "10.1371/journal.pone.0002745", "pmcid": "PMC2447878", "url": "https://pubmed.ncbi.nlm.nih.gov/18648514/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/18648514/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID18648514", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "null", "what_it_shows": "Early measured HIV-specific CD8 cytokine responses did not predict AIDS-free survival or CD4 decline.", "what_it_does_not_show": "Null immune-marker prediction does not refute HIV causation; the immunologic assay is a proxy.", "confounders_present": [ "Null immune-marker prediction does not refute HIV causation; the immunologic assay is a proxy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 4, "pmid": "10858179", "title": "Effect of hepatitis G virus infection on progression of HIV infection in patients with hemophilia. Multicenter Hemophilia Cohort Study.", "citation": "Yeo AE, Matsumoto A, Hisada M et al. Effect of hepatitis G virus infection on progression of HIV infection in patients with hemophilia. Multicenter Hemophilia Cohort Study. Annals of internal medicine. 2000.", "doi": "10.7326/0003-4819-132-12-200006200-00006", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/10858179/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/10858179/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID10858179", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "HGV-positive infected hemophiliacs had higher CD4 counts and better AIDS-free survival after adjustment.", "what_it_does_not_show": "Coinfection association with uncertain mechanism does not establish a required protective cause.", "confounders_present": [ "Coinfection association with uncertain mechanism does not establish a required protective cause." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 5, "pmid": "12803997", "title": "Early viral load and CD4+ T cell count, but not percentage of CCR5+ or CXCR4+ CD4+ T cells, are associated with R5-to-X4 HIV type 1 virus evolution.", "citation": "van Rij RP, Hazenberg MD, van Benthem BH et al. Early viral load and CD4+ T cell count, but not percentage of CCR5+ or CXCR4+ CD4+ T cells, are associated with R5-to-X4 HIV type 1 virus evolution. AIDS research and human retroviruses. 2003.", "doi": "10.1089/088922203765551737", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/12803997/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/12803997/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID12803997", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Early viral RNA and CD4 counts predicted later phenotype evolution; selected receptor percentages did not.", "what_it_does_not_show": "Correlated host and viral measurements do not identify an independently necessary receptor mechanism.", "confounders_present": [ "Correlated host and viral measurements do not identify an independently necessary receptor mechanism." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 6, "pmid": "10609356", "title": "[The prognostic markers of HIV infection progression. A study of the p24 antigen in a cohort of 251 patients].", "citation": "Rubio Caballero M, Nogués Biau A, Falguera Sacrest M et al. [The prognostic markers of HIV infection progression. A study of the p24 antigen in a cohort of 251 patients]. Anales de medicina interna (Madrid, Spain : 1984). 1999.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/10609356/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/10609356/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "SPANISH_251", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Higher and unstable p24 predicted AIDS or death over 24 months in a 251-patient cohort.", "what_it_does_not_show": "A prognostic biomarker is not a selective causal intervention; same cohort as PMID11109648.", "confounders_present": [ "A prognostic biomarker is not a selective causal intervention; same cohort as PMID11109648." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [ "Shared parent recruitment or randomization and related outcome ascertainment: SPANISH_251" ] }, { "n": 7, "pmid": "11109648", "title": "[The prognostic markers of survival and progression in HIV-1 infection. A study of CD4+ lymphocytes, antigen p24 and viral load during 3 years in a cohort of 251 patients].", "citation": "Rubio Caballero M, Nogués Biau A, Falguera Sacrest M et al. [The prognostic markers of survival and progression in HIV-1 infection. A study of CD4+ lymphocytes, antigen p24 and viral load during 3 years in a cohort of 251 patients]. Anales de medicina interna (Madrid, Spain : 1984). 2000.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/11109648/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/11109648/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "SPANISH_251", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "p24 and CD4 predicted three-year outcomes, with reported discrepancies against viral-load comparisons.", "what_it_does_not_show": "Same 251-patient cohort as PMID10609356; discrepancies prevent treating all biomarkers as equivalent.", "confounders_present": [ "Same 251-patient cohort as PMID10609356; discrepancies prevent treating all biomarkers as equivalent." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [ "Shared parent recruitment or randomization and related outcome ascertainment: SPANISH_251" ] }, { "n": 8, "pmid": "2242420", "title": "Silent infections with human immunodeficiency virus type 1 are highly unlikely in multitransfused seronegative hemophiliacs.", "citation": "Gibbons J, Cory JM, Hewlett IK et al. Silent infections with human immunodeficiency virus type 1 are highly unlikely in multitransfused seronegative hemophiliacs. Blood. 1990.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/2242420/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/2242420/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID2242420", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Serially followed seronegative multitransfused hemophiliacs showed little evidence of silent infection.", "what_it_does_not_show": "This bounds diagnostic failure in a selected exposed cohort; it is not a general absence-of-disease necessity experiment.", "confounders_present": [ "This bounds diagnostic failure in a selected exposed cohort; it is not a general absence-of-disease necessity experiment." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 9, "pmid": "9674733", "title": "The effect of monoclonal or ion-exchange purified factor VIII concentrate on HIV disease progression: a prospective cohort comparison.", "citation": "Hay CR, Ludlam CA, Lowe GD et al. The effect of monoclonal or ion-exchange purified factor VIII concentrate on HIV disease progression: a prospective cohort comparison. British journal of haematology. 1998.", "doi": "10.1046/j.1365-2141.1998.00753.x", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/9674733/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/9674733/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID9674733", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "null", "what_it_shows": "Two higher-purity factor VIII cohorts had similar CD4 decline, survival and AIDS illness rates.", "what_it_does_not_show": "Both cohorts were HIV infected and nonrandomized; no seronegative comparator and baseline CD4 differed.", "confounders_present": [ "Both cohorts were HIV infected and nonrandomized; no seronegative comparator and baseline CD4 differed." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 10, "pmid": "16011588", "title": "Progression of HIV infection in the post-HAART era among a cohort of HIV+ Greek haemophilia patients.", "citation": "Katsarou O, Touloumi G, Antoniou A et al. Progression of HIV infection in the post-HAART era among a cohort of HIV+ Greek haemophilia patients. Haemophilia : the official journal of the World Federation of Hemophilia. 2005.", "doi": "10.1111/j.1365-2516.2005.01109.x", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/16011588/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/16011588/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID16011588", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "AIDS risk fell in the post-HAART hemophilia cohort while non-AIDS mortality rose.", "what_it_does_not_show": "Historical periods differ in care, survival and liver disease; AIDS and all-cause mortality remain distinct.", "confounders_present": [ "Historical periods differ in care, survival and liver disease; AIDS and all-cause mortality remain distinct." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 11, "pmid": "7974372", "title": "Clinical factors associated with progression to AIDS in the Italian cohort of HIV-positive hemophiliacs. G.I.C.C. Gruppo Italiano Coagulopatie Congenite.", "citation": "Schinaia N, Ghirardini AM, Mazzucconi MG et al. Clinical factors associated with progression to AIDS in the Italian cohort of HIV-positive hemophiliacs. G.I.C.C. Gruppo Italiano Coagulopatie Congenite. Thrombosis and haemostasis. 1994.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7974372/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/7974372/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID7974372", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Italian infected hemophiliacs developed AIDS after estimated seroconversion, with age and treatment-associated heterogeneity.", "what_it_does_not_show": "Estimated infection times and nonrandomized factor exposure leave confounding.", "confounders_present": [ "Estimated infection times and nonrandomized factor exposure leave confounding." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 12, "pmid": "11511825", "title": "Homozygous and heterozygous CCR5-Delta32 genotypes are associated with resistance to HIV infection.", "citation": "Marmor M, Sheppard HW, Donnell D et al. Homozygous and heterozygous CCR5-Delta32 genotypes are associated with resistance to HIV infection. Journal of acquired immune deficiency syndromes (1999). 2001.", "doi": "10.1097/00126334-200108150-00009", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/11511825/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/11511825/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID11511825", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "CCR5 deletion genotypes were associated with lower acquisition risk in high-risk seronegative cohorts.", "what_it_does_not_show": "Genotype associations and exposure reporting do not prove absolute resistance or suffice as AIDS-necessity evidence alone.", "confounders_present": [ "Genotype associations and exposure reporting do not prove absolute resistance or suffice as AIDS-necessity evidence alone." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 13, "pmid": "15166526", "title": "Differences in disease progression in a cohort of long-term non-progressors after more than 16 years of HIV-1 infection.", "citation": "Rodés B, Toro C, Paxinos E et al. Differences in disease progression in a cohort of long-term non-progressors after more than 16 years of HIV-1 infection. AIDS (London, England). 2004.", "doi": "10.1097/00002030-200405210-00004", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/15166526/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/15166526/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID15166526", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Some long-term nonprogressors lost CD4 stability with detectable viremia, while others remained controlled.", "what_it_does_not_show": "Selected survivors and small samples do not establish inevitable progression or a universal protective mechanism.", "confounders_present": [ "Selected survivors and small samples do not establish inevitable progression or a universal protective mechanism." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 14, "pmid": "10352317", "title": "New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS.", "citation": "Hendel H, Caillat-Zucman S, Lebuanec H et al. New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS. Journal of immunology (Baltimore, Md. : 1950). 1999.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/10352317/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/10352317/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID10352317", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "HLA alleles associated with opposite AIDS progression patterns among selected extreme progressors.", "what_it_does_not_show": "Extreme selection, ancestry and multiple allele tests limit causal attribution and generalization.", "confounders_present": [ "Extreme selection, ancestry and multiple allele tests limit causal attribution and generalization." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 15, "pmid": "10559343", "title": "A polymorphism in the regulatory region of the CC-chemokine receptor 5 gene influences perinatal transmission of human immunodeficiency virus type 1 to African-American infants.", "citation": "Kostrikis LG, Neumann AU, Thomson B et al. A polymorphism in the regulatory region of the CC-chemokine receptor 5 gene influences perinatal transmission of human immunodeficiency virus type 1 to African-American infants. Journal of virology. 1999.", "doi": "10.1128/JVI.73.12.10264-10271.1999", "pmcid": "PMC113080", "url": "https://pubmed.ncbi.nlm.nih.gov/10559343/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/10559343/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID10559343", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "A host regulatory genotype associated with higher perinatal acquisition in untreated mother-infant pairs.", "what_it_does_not_show": "Ethnic frequency and subgroup associations do not establish necessity or individual infection certainty.", "confounders_present": [ "Ethnic frequency and subgroup associations do not establish necessity or individual infection certainty." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 16, "pmid": "24098976", "title": "Influence of CCR5 and CCR2 genetic variants in the resistance/susceptibility to HIV in serodiscordant couples from Colombia.", "citation": "Zapata W, Aguilar-Jiménez W, Pineda-Trujillo N et al. Influence of CCR5 and CCR2 genetic variants in the resistance/susceptibility to HIV in serodiscordant couples from Colombia. AIDS research and human retroviruses. 2013.", "doi": "10.1089/aid.2012.0299", "pmcid": "PMC3848445", "url": "https://pubmed.ncbi.nlm.nih.gov/24098976/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24098976/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID24098976", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Selected receptor allele frequencies differed among infected, exposed seronegative and healthy Colombian groups.", "what_it_does_not_show": "Small observational comparisons and multiple variants require replication; no homozygous deletion was found.", "confounders_present": [ "Small observational comparisons and multiple variants require replication; no homozygous deletion was found." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 17, "pmid": "13678468", "title": "Polymorphisms in the CCR5 coding and noncoding regions among HIV type 1-exposed, persistently seronegative female sex-workers from Thailand.", "citation": "Yang C, Li M, Limpakarnjanarat K et al. Polymorphisms in the CCR5 coding and noncoding regions among HIV type 1-exposed, persistently seronegative female sex-workers from Thailand. AIDS research and human retroviruses. 2003.", "doi": "10.1089/088922203322280883", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/13678468/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/13678468/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID13678468", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Thai exposed seronegative women did not show significant overall haplogroup differences from comparison groups.", "what_it_does_not_show": "Very small groups and a suggested two-person pattern do not validate a protective causal instrument.", "confounders_present": [ "Very small groups and a suggested two-person pattern do not validate a protective causal instrument." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 18, "pmid": "18648518", "title": "CCR5Delta32 genotypes in a German HIV-1 seroconverter cohort and report of HIV-1 infection in a CCR5Delta32 homozygous individual.", "citation": "Oh DY, Jessen H, Kücherer C et al. CCR5Delta32 genotypes in a German HIV-1 seroconverter cohort and report of HIV-1 infection in a CCR5Delta32 homozygous individual. PloS one. 2008.", "doi": "10.1371/journal.pone.0002747", "pmcid": "PMC2453227", "url": "https://pubmed.ncbi.nlm.nih.gov/18648518/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/18648518/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID18648518", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Deletion heterozygotes had lower viral setpoints and slower CD4 deterioration, but an infected homozygote progressed rapidly.", "what_it_does_not_show": "Host protection is incomplete; rare homozygote infection contradicts an absolute genotype barrier, not HIV causation.", "confounders_present": [ "Host protection is incomplete; rare homozygote infection contradicts an absolute genotype barrier, not HIV causation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 19, "pmid": "12271718", "title": "[The HIV-infection outbreak in the town Lys'va (Perm region): homozygote genotype CCR5 delta32/CCR5 delta32 provides the high level of the persistence in the parenteral transmission of the virus].", "citation": "Riabov GS, Kazennova EV, Korepanova LB et al. [The HIV-infection outbreak in the town Lys'va (Perm region): homozygote genotype CCR5 delta32/CCR5 delta32 provides the high level of the persistence in the parenteral transmission of the virus]. Voprosy virusologii. 2002.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/12271718/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/12271718/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID12271718", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "A deletion genotype was enriched among exposed uninfected people in a documented local outbreak.", "what_it_does_not_show": "Small observational exposure contrasts with population controls leave ancestry and exposure-dose confounding.", "confounders_present": [ "Small observational exposure contrasts with population controls leave ancestry and exposure-dose confounding." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 20, "pmid": "19433914", "title": "Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection.", "citation": "Parczewski M, Leszczyszyn-Pynka M, Kaczmarczyk M et al. Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection. Journal of applied genetics. 2009.", "doi": "10.1007/BF03195668", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/19433914/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/19433914/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID19433914", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "CCR5 variants differed between HIV-positive adults and neonatal population controls.", "what_it_does_not_show": "Different-age and exposure-unmatched controls cannot establish a clean resistance natural experiment.", "confounders_present": [ "Different-age and exposure-unmatched controls cannot establish a clean resistance natural experiment." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 21, "pmid": "24719475", "title": "HLA class I and KIR genes do not protect against HIV type 1 infection in highly exposed uninfected individuals with hemophilia A.", "citation": "Vince N, Bashirova AA, Lied A et al. HLA class I and KIR genes do not protect against HIV type 1 infection in highly exposed uninfected individuals with hemophilia A. The Journal of infectious diseases. 2014.", "doi": "10.1093/infdis/jiu214", "pmcid": "PMC4215081", "url": "https://pubmed.ncbi.nlm.nih.gov/24719475/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24719475/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID24719475", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "null", "what_it_shows": "Tested HLA and KIR configurations did not explain resistance in exposed uninfected hemophiliacs.", "what_it_does_not_show": "Negative selected genetic associations do not refute HIV causation or rule out other protective pathways.", "confounders_present": [ "Negative selected genetic associations do not refute HIV causation or rule out other protective pathways." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 22, "pmid": "16999868", "title": "Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals.", "citation": "Trecarichi EM, Tumbarello M, de Gaetano Donati K et al. Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals. AIDS research and therapy. 2006.", "doi": "10.1186/1742-6405-3-22", "pmcid": "PMC1592103", "url": "https://pubmed.ncbi.nlm.nih.gov/16999868/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/16999868/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID16999868", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Deletion heterozygosity was more frequent in a small exposed seronegative Italian group.", "what_it_does_not_show": "Small selected observational cohorts and self-reported exposure restrict instrument validity.", "confounders_present": [ "Small selected observational cohorts and self-reported exposure restrict instrument validity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 23, "pmid": "16865553", "title": "Gene polymorphisms in CCR5, CCR2, CX3CR1, SDF-1 and RANTES in exposed but uninfected partners of HIV-1 infected individuals in North India.", "citation": "Suresh P, Wanchu A, Sachdeva RK et al. Gene polymorphisms in CCR5, CCR2, CX3CR1, SDF-1 and RANTES in exposed but uninfected partners of HIV-1 infected individuals in North India. Journal of clinical immunology. 2006.", "doi": "10.1007/s10875-006-9036-0", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/16865553/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/16865553/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID not supplied" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID16865553", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "null", "what_it_shows": "Tested variants were not significantly associated with resistance in exposed North Indian partners.", "what_it_does_not_show": "Small sample and an unexamined linked erratum limit inference; null variants are not proof that host factors never matter.", "confounders_present": [ "Small sample and an unexamined linked erratum limit inference; null variants are not proof that host factors never matter." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 24, "pmid": "20930640", "title": "Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection.", "citation": "Baker JV, Neuhaus J, Duprez D et al. Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection. Journal of acquired immune deficiency syndromes (1999). 2011.", "doi": "10.1097/QAI.0b013e3181f7f61a", "pmcid": "PMC3005856", "url": "https://pubmed.ncbi.nlm.nih.gov/20930640/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/20930640/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "SMART", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Immediate ART improved CD4 counts and reduced D-dimer relative to deferred treatment, with other inflammatory markers null.", "what_it_does_not_show": "SMART secondary biomarker report is not independent clinical replication and biomarkers alone do not prove AIDS prevention.", "confounders_present": [ "SMART secondary biomarker report is not independent clinical replication and biomarkers alone do not prove AIDS prevention." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [ "Shared parent recruitment or randomization and related outcome ascertainment: SMART" ] }, { "n": 25, "pmid": "18476292", "title": "Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study.", "citation": "Strategies for Management of Antiretroviral Therapy (SMART) Study Group, Emery S, Neuhaus JA et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. The Journal of infectious diseases. 2008.", "doi": "10.1086/586713", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/18476292/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/18476292/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "SMART", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "SMART baseline untreated subgroup had more clinical events under the deferral strategy.", "what_it_does_not_show": "Secondary subgroup and wide intervals; grouped with SMART, not an independent randomization.", "confounders_present": [ "Secondary subgroup and wide intervals; grouped with SMART, not an independent randomization." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [ "Shared parent recruitment or randomization and related outcome ascertainment: SMART" ] }, { "n": 26, "pmid": "8624759", "title": "Patterns of opportunistic infections in patients with HIV infection.", "citation": "Finkelstein DM, Williams PL, Molenberghs G et al. Patterns of opportunistic infections in patients with HIV infection. Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association. 1996.", "doi": "10.1097/00042560-199605010-00006", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/8624759/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/8624759/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID8624759", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Prior opportunistic infections predicted later infections even after CD4 adjustment in two clinical-trial cohorts.", "what_it_does_not_show": "Within-infection prognosis is not direct HIV acquisition causality; parent cohorts may overlap other ART reports.", "confounders_present": [ "Within-infection prognosis is not direct HIV acquisition causality; parent cohorts may overlap other ART reports." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 27, "pmid": "9393380", "title": "Predicting outcomes in HIV-infected veterans: II. Survival after AIDS.", "citation": "Rabeneck L, Hartigan PM, Huang IW et al. Predicting outcomes in HIV-infected veterans: II. Survival after AIDS. Journal of clinical epidemiology. 1997.", "doi": "10.1016/s0895-4356(97)00182-0", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/9393380/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/9393380/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID9393380", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Age, CD4, first AIDS condition and function predicted survival among veterans developing AIDS.", "what_it_does_not_show": "Secondary clinical-staging analysis is not an independent intervention test.", "confounders_present": [ "Secondary clinical-staging analysis is not an independent intervention test." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 28, "pmid": "2685984", "title": "Zidovudine treatment of AIDS and ARC in Denmark 1987.", "citation": "Teglbjaerg LL, Mathiesen LR, Søeberg B et al. Zidovudine treatment of AIDS and ARC in Denmark 1987. Scandinavian journal of infectious diseases. 1989.", "doi": "10.3109/00365548909167439", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/2685984/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/2685984/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID2685984", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Zidovudine-treated Danish patients showed CD4 and antigen changes and better mortality than historical controls, with toxicity.", "what_it_does_not_show": "Historical comparison cannot isolate drug effect from care and selection; no randomized untreated comparator.", "confounders_present": [ "Historical comparison cannot isolate drug effect from care and selection; no randomized untreated comparator." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 29, "pmid": "27806243", "title": "Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.", "citation": "Fowler MG, Qin M, Fiscus SA et al. Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention. The New England journal of medicine. 2016.", "doi": "10.1056/NEJMoa1511691", "pmcid": "PMC5214343", "url": "https://pubmed.ncbi.nlm.nih.gov/27806243/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27806243/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "NCT01061151+NCT01253538", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "PROMISE ART reduced early infant infection relative to zidovudine alone, while adverse maternal and neonatal outcomes differed.", "what_it_does_not_show": "Active comparators and competing toxicity prevent interpreting HIV-free survival as proof of universal harmlessness or AIDS sufficiency.", "confounders_present": [ "Active comparators and competing toxicity prevent interpreting HIV-free survival as proof of universal harmlessness or AIDS sufficiency." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 30, "pmid": "20647201", "title": "Early versus standard antiretroviral therapy for HIV-infected adults in Haiti.", "citation": "Severe P, Juste MA, Ambroise A et al. Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. The New England journal of medicine. 2010.", "doi": "10.1056/NEJMoa0910370", "pmcid": "PMC3676927", "url": "https://pubmed.ncbi.nlm.nih.gov/20647201/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/20647201/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "NCT00120510", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Randomized earlier ART in Haiti reduced deaths and incident tuberculosis compared with later initiation.", "what_it_does_not_show": "A specific baseline CD4 and care setting; treatment benefit does not imply every infected person necessarily progresses.", "confounders_present": [ "A specific baseline CD4 and care setting; treatment benefit does not imply every infected person necessarily progresses." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 31, "pmid": "10207545", "title": "HIV-1 RNA response to antiretroviral treatment in 1280 participants in the Delta Trial: an extended virology study.", "citation": "Delta Coordinating Committee, Delta Virology Committee. HIV-1 RNA response to antiretroviral treatment in 1280 participants in the Delta Trial: an extended virology study. AIDS (London, England). 1999.", "doi": "10.1097/00002030-199901140-00008", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/10207545/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/10207545/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID10207545", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Randomized Delta regimens produced differing RNA suppression; attained RNA nadir predicted subsequent survival.", "what_it_does_not_show": "Within-trial mediator association is not randomized viral-load assignment; an extended report shares parent randomization.", "confounders_present": [ "Within-trial mediator association is not randomized viral-load assignment; an extended report shares parent randomization." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 32, "pmid": "21596680", "title": "Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)--associated tuberculous meningitis.", "citation": "Török ME, Yen NT, Chau TT et al. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)--associated tuberculous meningitis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2011.", "doi": "10.1093/cid/cir230", "pmcid": "PMC4340579", "url": "https://pubmed.ncbi.nlm.nih.gov/21596680/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/21596680/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID21596680", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "Immediate ART did not improve mortality or AIDS-event/death timing in HIV-associated tuberculous meningitis and increased grade-four harms.", "what_it_does_not_show": "A timing contrast in severe CNS infection does not test eliminating HIV versus persistent infection or refute its causal antecedence.", "confounders_present": [ "A timing contrast in severe CNS infection does not test eliminating HIV versus persistent infection or refute its causal antecedence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 33, "pmid": "8627060", "title": "Randomized study of the tolerance and efficacy of high- versus low-dose zidovudine in human immunodeficiency virus-infected children with mild to moderate symptoms (AIDS Clinical Trials Group 128). Pediatric AIDS Clinical Trials Group.", "citation": "Brady MT, McGrath N, Brouwers P et al. Randomized study of the tolerance and efficacy of high- versus low-dose zidovudine in human immunodeficiency virus-infected children with mild to moderate symptoms (AIDS Clinical Trials Group 128). Pediatric AIDS Clinical Trials Group. The Journal of infectious diseases. 1996.", "doi": "10.1093/infdis/173.5.1097", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/8627060/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/8627060/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID8627060", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "Double-blind high- versus low-dose zidovudine in children showed no efficacy or tolerance difference.", "what_it_does_not_show": "Two active regimens do not establish efficacy against no treatment or monotonic benefit from greater dosage.", "confounders_present": [ "Two active regimens do not establish efficacy against no treatment or monotonic benefit from greater dosage." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 34, "pmid": "1977079", "title": "A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group.", "citation": "Fischl MA, Parker CB, Pettinelli C et al. A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group. The New England journal of medicine. 1990.", "doi": "10.1056/NEJM199010113231501", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/1977079/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/1977079/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID1977079", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Lower-dose zidovudine improved survival versus the standard dose and reduced selected toxicities, without changing OI timing.", "what_it_does_not_show": "Active-dose comparison separates dose toxicity from virus causation and does not supply independent untreated counterfactual.", "confounders_present": [ "Active-dose comparison separates dose toxicity from virus causation and does not supply independent untreated counterfactual." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 35, "pmid": "17453591", "title": "A randomised control trial of structured interrupted generic antiretroviral therapy versus continuous therapy in HIV-infected individuals in Southern India.", "citation": "Kumarasamy N, Flanigan TP, Vallabhaneni S et al. A randomised control trial of structured interrupted generic antiretroviral therapy versus continuous therapy in HIV-infected individuals in Southern India. AIDS care. 2007.", "doi": "10.1080/09540120701213849", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/17453591/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/17453591/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID17453591", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "A small short-cycle interruption trial maintained CD4 above its primary threshold with few virologic failures and no deaths.", "what_it_does_not_show": "Only 35 randomized people and brief follow-up; not the same interruption strategy or endpoint as SMART.", "confounders_present": [ "Only 35 randomized people and brief follow-up; not the same interruption strategy or endpoint as SMART." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 36, "pmid": "29020361", "title": "Higher Mortality Despite Early Antiretroviral Therapy in Human Immunodeficiency Virus and Hepatitis B Virus (HBV)-Coinfected Patients With High HBV Replication.", "citation": "Kouamé GM, Boyd A, Moh R et al. Higher Mortality Despite Early Antiretroviral Therapy in Human Immunodeficiency Virus and Hepatitis B Virus (HBV)-Coinfected Patients With High HBV Replication. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018.", "doi": "10.1093/cid/cix747", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/29020361/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29020361/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "TEMPRANO", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "High HBV replication predicted mortality despite early ART, without interaction by ART strategy.", "what_it_does_not_show": "TEMPRANO secondary cohort; coinfection mortality is not equivalent to HIV-independent AIDS.", "confounders_present": [ "TEMPRANO secondary cohort; coinfection mortality is not equivalent to HIV-independent AIDS." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [ "Shared parent recruitment or randomization and related outcome ascertainment: TEMPRANO" ] }, { "n": 37, "pmid": "18525035", "title": "Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission.", "citation": "Kumwenda NI, Hoover DR, Mofenson LM et al. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission. The New England journal of medicine. 2008.", "doi": "10.1056/NEJMoa0801941", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/18525035/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/18525035/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "ErratumIn: PMID29898374" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "NCT00115648", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Extended infant antiretroviral prophylaxis reduced postnatal HIV acquisition relative to the control strategy.", "what_it_does_not_show": "Acquisition rather than AIDS is the endpoint; a linked correction is retained and its details were not examined.", "confounders_present": [ "Acquisition rather than AIDS is the endpoint; a linked correction is retained and its details were not examined." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 38, "pmid": "12126721", "title": "Effect of perinatal short-course zidovudine on the clinical and virological manifestations of HIV-1 subtype E infection in infants.", "citation": "Sutthent R, Chokephaibulkit K, Piyasujabul D et al. Effect of perinatal short-course zidovudine on the clinical and virological manifestations of HIV-1 subtype E infection in infants. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2002.", "doi": "10.1016/s1386-6532(01)00258-x", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/12126721/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/12126721/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID12126721", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Among twelve infected infants, prior prophylaxis exposure associated with more early symptoms and higher viral measurements.", "what_it_does_not_show": "Conditioning on breakthrough infection and tiny samples creates selection bias; this does not estimate prophylaxis harm across all randomized infants.", "confounders_present": [ "Conditioning on breakthrough infection and tiny samples creates selection bias; this does not estimate prophylaxis harm across all randomized infants." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 39, "pmid": "26603917", "title": "Extended pre-exposure prophylaxis with lopinavir-ritonavir versus lamivudine to prevent HIV-1 transmission through breastfeeding up to 50 weeks in infants in Africa (ANRS 12174): a randomised controlled trial.", "citation": "Nagot N, Kankasa C, Tumwine JK et al. Extended pre-exposure prophylaxis with lopinavir-ritonavir versus lamivudine to prevent HIV-1 transmission through breastfeeding up to 50 weeks in infants in Africa (ANRS 12174): a randomised controlled trial. Lancet (London, England). 2016.", "doi": "10.1016/S0140-6736(15)00984-8", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26603917/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26603917/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "ErratumIn: PMID31232371" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "NCT00640263", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "Two active infant prophylaxis regimens had similar low acquisition rates, without superiority of one.", "what_it_does_not_show": "No placebo/no-prophylaxis arm; a linked correction was not examined and absolute causal prevention cannot be estimated from this comparison alone.", "confounders_present": [ "No placebo/no-prophylaxis arm; a linked correction was not examined and absolute causal prevention cannot be estimated from this comparison alone." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 40, "pmid": "2114801", "title": "Age and human immunodeficiency virus infection in persons with hemophilia in California.", "citation": "Holman RC, Gomperts ED, Jason JM et al. Age and human immunodeficiency virus infection in persons with hemophilia in California. American journal of public health. 1990.", "doi": "10.2105/ajph.80.8.967", "pmcid": "PMC1404766", "url": "https://pubmed.ncbi.nlm.nih.gov/2114801/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/2114801/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID2114801", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "California hemophilia surveillance documented HIV prevalence and age-associated cumulative AIDS after infection.", "what_it_does_not_show": "Serologic status was known in only part of the clinic population and no uninfected clinical counterfactual was reported in the examined passage.", "confounders_present": [ "Serologic status was known in only part of the clinic population and no uninfected clinical counterfactual was reported in the examined passage." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 41, "pmid": "12048367", "title": "Time to AIDS from 1992 to 1999 in HIV-1-infected subjects with known date of infection.", "citation": "Tassie JM, Grabar S, Lancar R et al. Time to AIDS from 1992 to 1999 in HIV-1-infected subjects with known date of infection. Journal of acquired immune deficiency syndromes (1999). 2002.", "doi": "10.1097/00042560-200205010-00011", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/12048367/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/12048367/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID12048367", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Known-date French infection cohorts had longer estimated time to AIDS across increasingly potent treatment eras.", "what_it_does_not_show": "Calendar and treatment selection confounding remain; model-estimated incubation is not observed universal lifespan.", "confounders_present": [ "Calendar and treatment selection confounding remain; model-estimated incubation is not observed universal lifespan." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 42, "pmid": "9825787", "title": "The rate of CD4 decline as a determinant of progression to AIDS independent of the most recent CD4 count. The Italian Seroconversion Study.", "citation": "Cozzi Lepri A, Sabin CA, Phillips AN et al. The rate of CD4 decline as a determinant of progression to AIDS independent of the most recent CD4 count. The Italian Seroconversion Study. Epidemiology and infection. 1998.", "doi": "10.1017/s095026889800140x", "pmcid": "PMC2809533", "url": "https://pubmed.ncbi.nlm.nih.gov/9825787/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/9825787/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID9825787", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Earlier CD4 slope predicted subsequent AIDS beyond latest count in seroconversion cohorts.", "what_it_does_not_show": "Prediction of disease trajectory does not itself manipulate the upstream virus.", "confounders_present": [ "Prediction of disease trajectory does not itself manipulate the upstream virus." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 43, "pmid": "1679845", "title": "More rapid progression to AIDS in older HIV-infected people: the role of CD4+ T-cell counts.", "citation": "Phillips AN, Lee CA, Elford J et al. More rapid progression to AIDS in older HIV-infected people: the role of CD4+ T-cell counts. Journal of acquired immune deficiency syndromes. 1991.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/1679845/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/1679845/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID1679845", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Older infected hemophiliacs progressed faster after seroconversion, including after CD4 adjustment.", "what_it_does_not_show": "Age and care confounding remain; heterogeneity rejects a single inevitable timetable.", "confounders_present": [ "Age and care confounding remain; heterogeneity rejects a single inevitable timetable." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 44, "pmid": "29965987", "title": "Impact of schistosome infection on long-term HIV/AIDS outcomes.", "citation": "Colombe S, Machemba R, Mtenga B et al. Impact of schistosome infection on long-term HIV/AIDS outcomes. PLoS neglected tropical diseases. 2018.", "doi": "10.1371/journal.pntd.0006613", "pmcid": "PMC6044552", "url": "https://pubmed.ncbi.nlm.nih.gov/29965987/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29965987/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID29965987", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Schistosome coinfection associated with slower adverse HIV outcomes, opposite the authors' original hypothesis.", "what_it_does_not_show": "Observational competing-risk analysis and immune modifiers are not evidence of AIDS without HIV.", "confounders_present": [ "Observational competing-risk analysis and immune modifiers are not evidence of AIDS without HIV." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 45, "pmid": "17683002", "title": "Baseline HIV type 1 coreceptor tropism predicts disease progression.", "citation": "Daar ES, Kesler KL, Petropoulos CJ et al. Baseline HIV type 1 coreceptor tropism predicts disease progression. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2007.", "doi": "10.1086/520650", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/17683002/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/17683002/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID not supplied" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID17683002", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Baseline viral phenotype predicted CD4 decline and clinical AIDS progression beyond selected covariates.", "what_it_does_not_show": "Phenotype is observational; a linked erratum was not examined and no operational assay inference is needed.", "confounders_present": [ "Phenotype is observational; a linked erratum was not examined and no operational assay inference is needed." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 46, "pmid": "18456875", "title": "Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors.", "citation": "Zonios DI, Falloon J, Bennett JE et al. Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors. Blood. 2008.", "doi": "10.1182/blood-2007-12-127878", "pmcid": "PMC2442741", "url": "https://pubmed.ncbi.nlm.nih.gov/18456875/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/18456875/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID not supplied" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID18456875", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Non-HIV idiopathic CD4 lymphocytopenia caused persistent low counts and opportunistic illnesses, including some AIDS-defining clinical conditions.", "what_it_does_not_show": "This refutes equating every AIDS-like clinical condition with HIV; a different syndrome is not direct refutation of HIV-associated AIDS causation. Linked correction is an author-name correction.", "confounders_present": [ "This refutes equating every AIDS-like clinical condition with HIV; a different syndrome is not direct refutation of HIV-associated AIDS causation. Linked correction is an author-name correction." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 47, "pmid": "24646462", "title": "Idiopathic CD4 lymphocytopenia: clinical and immunologic characteristics and follow-up of 40 patients.", "citation": "Régent A, Autran B, Carcelain G et al. Idiopathic CD4 lymphocytopenia: clinical and immunologic characteristics and follow-up of 40 patients. Medicine. 2014.", "doi": "10.1097/MD.0000000000000017", "pmcid": "PMC4616307", "url": "https://pubmed.ncbi.nlm.nih.gov/24646462/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24646462/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID24646462", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "A French ICL cohort showed heterogeneous immune deficiencies, opportunistic disease and deaths without HIV.", "what_it_does_not_show": "The generic low-CD4/OI phenotype has other causes; necessity must be evaluated for the HIV-associated syndrome rather than every immune-deficiency phenotype.", "confounders_present": [ "The generic low-CD4/OI phenotype has other causes; necessity must be evaluated for the HIV-associated syndrome rather than every immune-deficiency phenotype." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 48, "pmid": "33422677", "title": "Characterization of autoantibodies, immunophenotype and autoimmune disease in a prospective cohort of patients with idiopathic CD4 lymphocytopenia.", "citation": "Cudrici CD, Boulougoura A, Sheikh V et al. Characterization of autoantibodies, immunophenotype and autoimmune disease in a prospective cohort of patients with idiopathic CD4 lymphocytopenia. Clinical immunology (Orlando, Fla.). 2021.", "doi": "10.1016/j.clim.2021.108664", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33422677/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33422677/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID33422677", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Prospective ICL referral patients often had autoimmune features and altered immune-cell distributions.", "what_it_does_not_show": "Referral selection and unclear initiating mechanism prevent proving a competing universal cause of AIDS.", "confounders_present": [ "Referral selection and unclear initiating mechanism prevent proving a competing universal cause of AIDS." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 49, "pmid": "38376918", "title": "The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers.", "citation": "Gasca-Capote C, Lian X, Gao C et al. The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers. The Journal of clinical investigation. 2024.", "doi": "10.1172/JCI174215", "pmcid": "PMC11014653", "url": "https://pubmed.ncbi.nlm.nih.gov/38376918/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38376918/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID38376918", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Persistent and transient elite controllers differed in observed reservoir landscape before control loss.", "what_it_does_not_show": "Selected infected controllers show modification of course; reservoir comparisons alone do not prove a sufficient protective mechanism.", "confounders_present": [ "Selected infected controllers show modification of course; reservoir comparisons alone do not prove a sufficient protective mechanism." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 50, "pmid": "21084992", "title": "An additive effect of protective host genetic factors correlates with HIV nonprogression status.", "citation": "Salgado M, Simón A, Sanz-Minguela B et al. An additive effect of protective host genetic factors correlates with HIV nonprogression status. Journal of acquired immune deficiency syndromes (1999). 2011.", "doi": "10.1097/QAI.0b013e3182036f14", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/21084992/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/21084992/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID21084992", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Protective host alleles collectively associated with nonprogression, with prominent HLA effects.", "what_it_does_not_show": "Small selected genetic combinations and additive associations do not establish absolute protection or independence from infection.", "confounders_present": [ "Small selected genetic combinations and additive associations do not establish absolute protection or independence from infection." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 51, "pmid": "26192873", "title": "Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.", "citation": "INSIGHT START Study Group, Lundgren JD, Babiker AG et al. 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No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "what_it_does_not_show": "Specific interruption strategy and previously treated population; mediator adjustment is not perfect causal mediation and toxicity/coinfections still matter.", "confounders_present": [ "Specific interruption strategy and previously treated population; mediator adjustment is not perfect causal mediation and toxicity/coinfections still matter." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [ "Shared parent recruitment or randomization and related outcome ascertainment: SMART" ] }, { "n": 53, "pmid": "26193126", "title": "A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa.", "citation": "TEMPRANO ANRS 12136 Study Group, Danel C, Moh R et al. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. The New England journal of medicine. 2015.", "doi": "10.1056/NEJMoa1507198", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26193126/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26193126/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "TEMPRANO", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "TEMPRANO early ART and tuberculosis preventive treatment independently reduced severe clinical illness or death.", "what_it_does_not_show": "Combined clinical composite and setting-specific coinfection prevention; ART and IPT are separate interventions, not proof that all mortality is HIV alone.", "confounders_present": [ "Combined clinical composite and setting-specific coinfection prevention; ART and IPT are separate interventions, not proof that all mortality is HIV alone." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [ "Shared parent recruitment or randomization and related outcome ascertainment: TEMPRANO" ] }, { "n": 54, "pmid": "3299089", "title": "The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. 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No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Double-blind AZT versus placebo reduced deaths and opportunistic infections over short follow-up with improved function.", "what_it_does_not_show": "Selected advanced disease, early termination and drug toxicity limit magnitude and long-term inference; one drug alone does not settle mechanism specificity.", "confounders_present": [ "Selected advanced disease, early termination and drug toxicity limit magnitude and long-term inference; one drug alone does not settle mechanism specificity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 55, "pmid": "8638160", "title": "Prognosis in HIV-1 infection predicted by the quantity of virus in plasma.", "citation": "Mellors JW, Rinaldo CR, Gupta P et al. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science (New York, N.Y.). 1996.", "doi": "10.1126/science.272.5265.1167", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/8638160/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/8638160/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID not supplied" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID8638160", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Baseline plasma RNA predicted AIDS and death over long follow-up in 180 infected men beyond CD4 prognostic value.", "what_it_does_not_show": "Primary cohort despite a Comment indexing tag; observation alone does not establish causation and a linked erratum was not examined.", "confounders_present": [ "Primary cohort despite a Comment indexing tag; observation alone does not establish causation and a linked erratum was not examined." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 56, "pmid": "21091279", "title": "Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.", "citation": "Grant RM, Lama JR, Anderson PL et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. The New England journal of medicine. 2010.", "doi": "10.1056/NEJMoa1011205", "pmcid": "PMC3079639", "url": "https://pubmed.ncbi.nlm.nih.gov/21091279/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/21091279/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "NCT00458393", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "iPrEx prophylaxis reduced new HIV acquisition versus placebo; measured exposure correlated with protection.", "what_it_does_not_show": "Acquisition not AIDS is the randomized endpoint; postrandomization measured exposure association is not independently randomized adherence.", "confounders_present": [ "Acquisition not AIDS is the randomized endpoint; postrandomization measured exposure association is not independently randomized adherence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 57, "pmid": "22784037", "title": "Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.", "citation": "Baeten JM, Donnell D, Ndase P et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. The New England journal of medicine. 2012.", "doi": "10.1056/NEJMoa1108524", "pmcid": "PMC3770474", "url": "https://pubmed.ncbi.nlm.nih.gov/22784037/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22784037/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "NCT00557245", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Partners PrEP active regimens reduced HIV acquisition versus placebo in serodiscordant couples.", "what_it_does_not_show": "The pathway endpoint is infection incidence, not ultimate AIDS necessity or sufficiency; adherence and context matter.", "confounders_present": [ "The pathway endpoint is infection incidence, not ultimate AIDS necessity or sufficiency; adherence and context matter." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 58, "pmid": "21767103", "title": "Prevention of HIV-1 infection with early antiretroviral therapy.", "citation": "Cohen MS, Chen YQ, McCauley M et al. Prevention of HIV-1 infection with early antiretroviral therapy. The New England journal of medicine. 2011.", "doi": "10.1056/NEJMoa1105243", "pmcid": "PMC3200068", "url": "https://pubmed.ncbi.nlm.nih.gov/21767103/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/21767103/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "HPTN052", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "HPTN052 early treatment reduced linked partner acquisition and clinical events.", "what_it_does_not_show": "Transmission and clinical follow-up share the same randomization as PMID24602844 and cannot be counted as separate causal lines.", "confounders_present": [ "Transmission and clinical follow-up share the same randomization as PMID24602844 and cannot be counted as separate causal lines." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [ "Shared parent recruitment or randomization and related outcome ascertainment: HPTN052" ] }, { "n": 59, "pmid": "7935654", "title": "Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.", "citation": "Connor EM, Sperling RS, Gelber R et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. The New England journal of medicine. 1994.", "doi": "10.1056/NEJM199411033311801", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7935654/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/7935654/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID7935654", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Randomized maternal/infant zidovudine reduced infant acquisition versus placebo.", "what_it_does_not_show": "An acquisition-prevention link complements progression trials but alone does not prove downstream AIDS inevitability or drug harmlessness.", "confounders_present": [ "An acquisition-prevention link complements progression trials but alone does not prove downstream AIDS inevitability or drug harmlessness." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 60, "pmid": "19020325", "title": "Early antiretroviral therapy and mortality among HIV-infected infants.", "citation": "Violari A, Cotton MF, Gibb DM et al. Early antiretroviral therapy and mortality among HIV-infected infants. The New England journal of medicine. 2008.", "doi": "10.1056/NEJMoa0800971", "pmcid": "PMC2950021", "url": "https://pubmed.ncbi.nlm.nih.gov/19020325/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/19020325/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "NCT00102960", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph4, 1:Results:paragraph6, 1:Results:paragraph7. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages.", "what_it_does_not_show": "Infant baseline eligibility, limited early follow-up and reassessment after stopping restrict extrapolation; no infection-alone sufficiency proof.", "confounders_present": [ "Infant baseline eligibility, limited early follow-up and reassessment after stopping restrict extrapolation; no infection-alone sufficiency proof." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 61, "pmid": "24602844", "title": "Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial.", "citation": "Grinsztejn B, Hosseinipour MC, Ribaudo HJ et al. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial. The Lancet. Infectious diseases. 2014.", "doi": "10.1016/S1473-3099(13)70692-3", "pmcid": "PMC4144040", "url": "https://pubmed.ncbi.nlm.nih.gov/24602844/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24602844/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "ErratumIn: PMID not supplied" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "HPTN052", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 2:Results:paragraph1, 2:Results:paragraph2, 2:Results:paragraph4. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "HPTN052 follow-up reduced first AIDS events, while the primary clinical composite and mortality comparisons were not significant.", "what_it_does_not_show": "Same parent trial as PMID21767103; significant secondary outcomes must not be substituted for a positive primary composite.", "confounders_present": [ "Same parent trial as PMID21767103; significant secondary outcomes must not be substituted for a positive primary composite." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [ "Shared parent recruitment or randomization and related outcome ascertainment: HPTN052" ] }, { "n": 62, "pmid": "28301424", "title": "Joint estimation of CD4+ cell progression and survival in untreated individuals with HIV-1 infection.", "citation": "Mangal TD, UNAIDS Working Group on CD4 Progression and Mortality Amongst HIV Seroconverters including the CASCADE Collaboration in EuroCoord. Joint estimation of CD4+ cell progression and survival in untreated individuals with HIV-1 infection. AIDS (London, England). 2017.", "doi": "10.1097/QAD.0000000000001437", "pmcid": "PMC5414573", "url": "https://pubmed.ncbi.nlm.nih.gov/28301424/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28301424/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "CASCADE_POOLED", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Pooled individual seroconverter trajectories showed CD4 deterioration and mortality varying by age and region.", "what_it_does_not_show": "Primary participant-data analysis shares contributing cohorts; modeled untreated survival and informative ART initiation are limitations.", "confounders_present": [ "Primary participant-data analysis shares contributing cohorts; modeled untreated survival and informative ART initiation are limitations." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [ "Shared parent recruitment or randomization and related outcome ascertainment: CASCADE_POOLED" ] }, { "n": 63, "pmid": "26423816", "title": "Characterisation of long-term non-progression of HIV-1 infection after seroconversion: a cohort study.", "citation": "van der Helm JJ, Geskus R, Lodi S et al. Characterisation of long-term non-progression of HIV-1 infection after seroconversion: a cohort study. The lancet. HIV. 2014.", "doi": "10.1016/S2352-3018(14)70016-5", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26423816/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26423816/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "CASCADE_POOLED", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Most selected long-term nonprogressors later lost status, with lower CD4 or higher RNA predicting loss.", "what_it_does_not_show": "Nonprogression requires untreated status and CD4 at least 500 as well as absence of AIDS; its percentages are not simply AIDS-free survival probabilities. CASCADE overlaps other cohort analyses.", "confounders_present": [ "Nonprogression requires untreated status and CD4 at least 500 as well as absence of AIDS; its percentages are not simply AIDS-free survival probabilities. CASCADE overlaps other cohort analyses." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [ "Shared parent recruitment or randomization and related outcome ascertainment: CASCADE_POOLED" ] } ], "verification_summary": { "load_bearing_claims_checked": 67, "verified": 67, "unverified": 0, "contradicted": 0, "note": "Verified attribution is distinct from mechanism truth or complete body access." }, "factual_issues_found": [], "cap_rules_applied": [], "cap_precedence_resolutions": [ { "collision": "Perturbation in a defined setting versus broader inference", "subclaim_scope_cap_binds_on": "HIV infection is the necessary cause of AIDS.", "subclaim_scope_threshold_binds_on": "The precise experimentally tested subclaim scope", "resolution": "Clinical interventions cross within prespecified human infection and baseline scopes. The universal pure-association cap binds each prognostic/allele-frequency report individually, not a causal set complemented by randomized clinical perturbation. The rubric is explicitly adapted to targeted viral treatment rather than broad immunosuppression. Non-HIV phenocopies constrain phenotype specificity; they are not discarded or relabeled as HIV infection.", "note": "Convergent lines are assessed as a set; one weak leg is not re-capped over the assembled case." } ], "boundary_check_BGD": [ { "subclaim_id": "SC1", "field_valid_perturbation_quote": "\n- Cell-type-specific conditional knockout or depletion\n- Pathway-specific blockade (not broad immunosuppression) changing disease course\n- Human targeted therapy with mechanistic alignment showing disease-modifying effect", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "PMID12487823, PMID26192873, PMID17135583, PMID19020325", "gamma_hard_rules_triggered": [ "The conclusion does not rest on inflammatory markers, ex vivo findings, or correlation alone.", "Human targeted suppression changes clinical progression; temporality, prevention and host susceptibility provide complementary causal constraints.", "Specific timing nulls, treatment toxicities and rare host protection are retained; infection alone is not universally sufficient." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "Documented seroconversion precedes immune deterioration across clinical exposure settings. This observational chain is interpreted together with randomized viral suppression and clinical rescue; it is not made causal by prognostic RNA correlations alone.", "ceiling_from_boundary_check": "Δ or higher" }, { "subclaim_id": "SC2", "field_valid_perturbation_quote": "\n- Cell-type-specific conditional knockout or depletion\n- Pathway-specific blockade (not broad immunosuppression) changing disease course\n- Human targeted therapy with mechanistic alignment showing disease-modifying effect", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "PMID20647201, PMID26192873, PMID17135583, PMID26193126, PMID3299089, PMID19020325, PMID24602844", "gamma_hard_rules_triggered": [ "The conclusion does not rest on inflammatory markers, ex vivo findings, or correlation alone.", "Human targeted suppression changes clinical progression; temporality, prevention and host susceptibility provide complementary causal constraints.", "Specific timing nulls, treatment toxicities and rare host protection are retained; infection alone is not universally sufficient." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "Earlier sustained ART improves CD4 and clinical outcomes, while interruption harms selected populations. Broad predictive consistency survives known timing and toxicity limits. Clinical suppression benefit is not infection-alone sufficiency.", "ceiling_from_boundary_check": "Δ or higher" }, { "subclaim_id": "SC3", "field_valid_perturbation_quote": "\n- Cell-type-specific conditional knockout or depletion\n- Pathway-specific blockade (not broad immunosuppression) changing disease course\n- Human targeted therapy with mechanistic alignment showing disease-modifying effect", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "PMID26192873, PMID17135583, PMID22784037, PMID21767103, PMID7935654, PMID19020325", "gamma_hard_rules_triggered": [ "The conclusion does not rest on inflammatory markers, ex vivo findings, or correlation alone.", "Human targeted suppression changes clinical progression; temporality, prevention and host susceptibility provide complementary causal constraints.", "Specific timing nulls, treatment toxicities and rare host protection are retained; infection alone is not universally sufficient." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "HIV is a necessary causal antecedent of the HIV-associated AIDS process under the registered clinical distinction, supported by convergent acquisition, temporality and suppression evidence rather than classification alone. Generic immunodeficiency has other causes. Host controllers and treatment change progression without removing the viral antecedent. Necessity does not imply inevitable AIDS.", "ceiling_from_boundary_check": "Δ or higher" } ], "thresholds_tested": [ { "subclaim_id": "SC1", "threshold": "Δ", "requirement_quoted": "Requires pathway- or cell-type-resolved causal perturbation affecting disease or phenotype.", "satisfied": "yes", "supporting_evidence": [ "[1] Documented seroconversion precedes increasing viral load and CD4 decline in 46 untreated Indian participants.", "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Ε", "requirement_quoted": "Requires context-specific causality with explicit scope restriction.", "satisfied": "yes", "supporting_evidence": [ "[1] Documented seroconversion precedes increasing viral load and CD4 decline in 46 untreated Indian participants.", "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Ζ", "requirement_quoted": "Requires multiple convergent causal manipulations and reduced plausibility of downstream-only interpretations.", "satisfied": "yes", "supporting_evidence": [ "[1] Documented seroconversion precedes increasing viral load and CD4 decline in 46 untreated Indian participants.", "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Η", "requirement_quoted": "Requires robust upstream causal evidence across systems and interventions.", "satisfied": "yes", "supporting_evidence": [ "[1] Documented seroconversion precedes increasing viral load and CD4 decline in 46 untreated Indian participants.", "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Θ", "requirement_quoted": "Requires predictive consistency and minimal contradiction in the claimed disease scope.", "satisfied": "no", "supporting_evidence": [ "[1] Documented seroconversion precedes increasing viral load and CD4 decline in 46 untreated Indian participants.", "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages." ], "what_would_cross_it": "Extend prospective consistency into the claimed clinical disease scope with independently validated etiologic ascertainment; existing broad inference is already supported by complementary targeted human interventions." }, { "subclaim_id": "SC2", "threshold": "Δ", "requirement_quoted": "Requires pathway- or cell-type-resolved causal perturbation affecting disease or phenotype.", "satisfied": "yes", "supporting_evidence": [ "[30] Randomized earlier ART in Haiti reduced deaths and incident tuberculosis compared with later initiation.", "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[53] TEMPRANO early ART and tuberculosis preventive treatment independently reduced severe clinical illness or death.", "[54] Double-blind AZT versus placebo reduced deaths and opportunistic infections over short follow-up with improved function.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages.", "[61] HPTN052 follow-up reduced first AIDS events, while the primary clinical composite and mortality comparisons were not significant." ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Ε", "requirement_quoted": "Requires context-specific causality with explicit scope restriction.", "satisfied": "yes", "supporting_evidence": [ "[30] Randomized earlier ART in Haiti reduced deaths and incident tuberculosis compared with later initiation.", "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[53] TEMPRANO early ART and tuberculosis preventive treatment independently reduced severe clinical illness or death.", "[54] Double-blind AZT versus placebo reduced deaths and opportunistic infections over short follow-up with improved function.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages.", "[61] HPTN052 follow-up reduced first AIDS events, while the primary clinical composite and mortality comparisons were not significant." ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Ζ", "requirement_quoted": "Requires multiple convergent causal manipulations and reduced plausibility of downstream-only interpretations.", "satisfied": "yes", "supporting_evidence": [ "[30] Randomized earlier ART in Haiti reduced deaths and incident tuberculosis compared with later initiation.", "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[53] TEMPRANO early ART and tuberculosis preventive treatment independently reduced severe clinical illness or death.", "[54] Double-blind AZT versus placebo reduced deaths and opportunistic infections over short follow-up with improved function.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages.", "[61] HPTN052 follow-up reduced first AIDS events, while the primary clinical composite and mortality comparisons were not significant." ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Η", "requirement_quoted": "Requires robust upstream causal evidence across systems and interventions.", "satisfied": "yes", "supporting_evidence": [ "[30] Randomized earlier ART in Haiti reduced deaths and incident tuberculosis compared with later initiation.", "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[53] TEMPRANO early ART and tuberculosis preventive treatment independently reduced severe clinical illness or death.", "[54] Double-blind AZT versus placebo reduced deaths and opportunistic infections over short follow-up with improved function.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages.", "[61] HPTN052 follow-up reduced first AIDS events, while the primary clinical composite and mortality comparisons were not significant." ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Θ", "requirement_quoted": "Requires predictive consistency and minimal contradiction in the claimed disease scope.", "satisfied": "yes", "supporting_evidence": [ "[30] Randomized earlier ART in Haiti reduced deaths and incident tuberculosis compared with later initiation.", "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[53] TEMPRANO early ART and tuberculosis preventive treatment independently reduced severe clinical illness or death.", "[54] Double-blind AZT versus placebo reduced deaths and opportunistic infections over short follow-up with improved function.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages.", "[61] HPTN052 follow-up reduced first AIDS events, while the primary clinical composite and mortality comparisons were not significant." ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Ω", "requirement_quoted": "Requires necessity and sufficiency of the immune mechanism within the claimed scope.", "satisfied": "no", "supporting_evidence": [ "[30] Randomized earlier ART in Haiti reduced deaths and incident tuberculosis compared with later initiation.", "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[53] TEMPRANO early ART and tuberculosis preventive treatment independently reduced severe clinical illness or death.", "[54] Double-blind AZT versus placebo reduced deaths and opportunistic infections over short follow-up with improved function.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages.", "[61] HPTN052 follow-up reduced first AIDS events, while the primary clinical composite and mortality comparisons were not significant." ], "what_would_cross_it": "Ω would require necessity and sufficiency of the precise immune mechanism under predetermined host and clinical conditions; suppression effects do not establish infection-alone sufficiency." }, { "subclaim_id": "SC3", "threshold": "Δ", "requirement_quoted": "Requires pathway- or cell-type-resolved causal perturbation affecting disease or phenotype.", "satisfied": "yes", "supporting_evidence": [ "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[57] Partners PrEP active regimens reduced HIV acquisition versus placebo in serodiscordant couples.", "[58] HPTN052 early treatment reduced linked partner acquisition and clinical events.", "[59] Randomized maternal/infant zidovudine reduced infant acquisition versus placebo.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages." ], "what_would_cross_it": "" }, { "subclaim_id": "SC3", "threshold": "Ε", "requirement_quoted": "Requires context-specific causality with explicit scope restriction.", "satisfied": "yes", "supporting_evidence": [ "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[57] Partners PrEP active regimens reduced HIV acquisition versus placebo in serodiscordant couples.", "[58] HPTN052 early treatment reduced linked partner acquisition and clinical events.", "[59] Randomized maternal/infant zidovudine reduced infant acquisition versus placebo.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages." ], "what_would_cross_it": "" }, { "subclaim_id": "SC3", "threshold": "Ζ", "requirement_quoted": "Requires multiple convergent causal manipulations and reduced plausibility of downstream-only interpretations.", "satisfied": "yes", "supporting_evidence": [ "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[57] Partners PrEP active regimens reduced HIV acquisition versus placebo in serodiscordant couples.", "[58] HPTN052 early treatment reduced linked partner acquisition and clinical events.", "[59] Randomized maternal/infant zidovudine reduced infant acquisition versus placebo.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages." ], "what_would_cross_it": "" }, { "subclaim_id": "SC3", "threshold": "Η", "requirement_quoted": "Requires robust upstream causal evidence across systems and interventions.", "satisfied": "yes", "supporting_evidence": [ "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[57] Partners PrEP active regimens reduced HIV acquisition versus placebo in serodiscordant couples.", "[58] HPTN052 early treatment reduced linked partner acquisition and clinical events.", "[59] Randomized maternal/infant zidovudine reduced infant acquisition versus placebo.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages." ], "what_would_cross_it": "" }, { "subclaim_id": "SC3", "threshold": "Θ", "requirement_quoted": "Requires predictive consistency and minimal contradiction in the claimed disease scope.", "satisfied": "yes", "supporting_evidence": [ "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[57] Partners PrEP active regimens reduced HIV acquisition versus placebo in serodiscordant couples.", "[58] HPTN052 early treatment reduced linked partner acquisition and clinical events.", "[59] Randomized maternal/infant zidovudine reduced infant acquisition versus placebo.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages." ], "what_would_cross_it": "" }, { "subclaim_id": "SC3", "threshold": "Ω", "requirement_quoted": "Requires necessity and sufficiency of the immune mechanism within the claimed scope.", "satisfied": "no", "supporting_evidence": [ "[51] START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression.", "[52] SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm.", "[57] Partners PrEP active regimens reduced HIV acquisition versus placebo in serodiscordant couples.", "[58] HPTN052 early treatment reduced linked partner acquisition and clinical events.", "[59] Randomized maternal/infant zidovudine reduced infant acquisition versus placebo.", "[60] CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages." ], "what_would_cross_it": "Ω would require both necessity and sufficiency under a noncircular, prospectively fixed clinical phenotype and host scope. Intentionally withholding effective care or inducing infection is not an acceptable test." } ], "generalization_check": { "generalization_tested": "yes", "context_boundary_mapped": "yes", "internal_negative_controls": [ "HIV-negative ICL cohorts demonstrate that low CD4 counts and opportunistic infections are not a specific HIV diagnostic signature.", "Small host-genetic nulls and infected CCR5 deletion homozygotes limit absolute-resistance claims.", "The tuberculous meningitis timing trial had no mortality benefit despite immediate treatment, constraining a universal immediate-benefit claim." ], "note": "Independent early-treatment benefits extend from adult cohorts with different baseline CD4 levels and regions to infected infants. Viral suppression and interruption are different directional tests. Universal timing, universal symptom specificity, all mortality causation and inevitable progression are not claimed." }, "falsification_patterns_met": [], "pitfalls_flagged": [ "Definitional circularity between HIV status and the AIDS syndrome definition; answered by intervention evidence rather than classification.", "Phenotype similarity treated as etiologic identity; non-HIV idiopathic CD4 lymphocytopenia excludes it.", "Prevention of acquisition conflated with modification of established disease.", "Repeated reports of one randomization (SMART, HPTN052) treated as independent causal lines." ], "causal_tally_audit": { "tally_claimed_by_document": 10, "tally_after_audit": 10, "tally_unit": "Positive qualifying study units across scoped subclaims, not independent causal lines or full-claim necessity/sufficiency.", "screened_discriminating_contrasts": 18, "items_rejected": [ "Null and negative contrasts are discriminators, not positive threshold crossings. Reports and replications are not independent causal lines.", "Repeat SMART and HPTN052 reports count once per shared parent contrast.", "Prevention incidence and clinical progression are different causal links; no trial establishes both infection-alone sufficiency and universal AIDS inevitability.", "Active-active dose/prophylaxis contrasts and null comparisons are discriminators, not positive nominal crossings." ] }, "steelman": { "case_one_rung_higher": "Case for Ω: exposure-to-disease and prevention/suppression findings support necessity, and untreated infection frequently precedes AIDS. But a necessary antecedent is not sufficient without host, persistence, time and disease context. Controllers, effective treatment and non-HIV phenocopies require predefined scope and do not allow infection-alone sufficiency.", "case_one_rung_lower": "Case for Η: clinical strategies are open-label and pharmacological, susceptibility cohorts are confounded, and many individual biomarkers fail. Yet blinded clinical event review, infant and adult randomized benefits, an interruption counter-direction test, and acquisition prevention provide consistent complementary prediction at the claimed scope. These weaknesses limit precision and confidence without reducing the clinical antecedent to an association.", "which_rejected": "Retain Θ for the registered HIV-associated clinical causal antecedent, with Moderate confidence for this bounded audit. Reject Ω for infection-alone sufficiency and reject a generic low-CD4 phenotype as the nominal disease definition.", "blocking_cap_threshold_or_missing_experiment": "Missing experiment: A stronger necessity-and-sufficiency assessment would require a prospectively specified noncircular syndrome definition and independently verified naturally acquired HIV status, host modifiers, exposure history and longitudinal outcomes. Use ethically delivered target-engaged treatment and adjudicated natural-course/clinical-care observations; do not induce infection or withhold effective therapy. The purpose is causal scope discrimination rather than recreating established treatment harm." }, "final_score": { "hsef_level": "Θ", "hsef_descriptor": "High predictive accuracy, minimal unresolved exceptions", "confidence": "High", "confidence_rationale": "Extensive independent replication across multinational seroconverter cohorts and randomized clinical trials (START, SMART, HPTN052, CHER, TEMPRANO, ACTG 076, iPrEx, Partners PrEP) establishes the evidence density and reproducibility the High band describes. The bounded access of this audit (3 selected partial-body examinations of 63 primary reports) is a limitation of what this review verified and is recorded under residual limitations; the framework sets the band from evidence density and reproducibility, not from reviewer access depth.", "rests_on_non_peer_reviewed_work": false, "rationale": "Overall Θ follows registered SC3. The convergent clinical causal case is strong and predictively consistent: documented acquisition precedes immune deterioration, suppression changes clinical trajectories, interrupted suppression worsens them, and prophylaxis prevents acquisition. Host and coinfection modifiers make infection insufficient for inevitable disease. Non-HIV ICL shows that low CD4/OI phenotypes are not HIV-specific; its existence does not erase the viral causal process established by intervention, but it blocks a broader claim that HIV is necessary for all acquired immunodeficiency." }, "role_of_mechanism": { "classification": "primary driver", "derivation_step_matched": 3, "derivation": "Acquisition is documented before immune deterioration, so the proposed infection is not solely a disease consequence (step 1). Targeted treatment changes immune and clinical trajectories, rejecting causal irrelevance (step 2). Initiation by infection and clinical dependency on continued viral activity justify primary driver at step 3 within the HIV-associated syndrome. OI organisms and host factors remain contributing causes; primary driver does not mean sole sufficient cause.", "tournament_used_as_tiebreaker": false, "note": "Derived from causal direction, not tournament rank." }, "extended_scoring_MSD": { "momentum": { "value": "Mechanistic only", "artifact": "Clinical intervention programs such as START (NCT00867048), CHER (NCT00102960), HPTN052 (NCT00074581) and contemporary elite-controller phenotyping (PMID38376918) continue mechanistic and treatment questions, but these examined completed programs do not constitute a named ongoing experiment that could prove infection-alone sufficiency. No verified next-Ω experiment is claimed.", "justification": "Clinical intervention programs such as START (NCT00867048), CHER (NCT00102960), HPTN052 (NCT00074581) and contemporary elite-controller phenotyping (PMID38376918) continue mechanistic and treatment questions, but these examined completed programs do not constitute a named ongoing experiment that could prove infection-alone sufficiency. No verified next-Ω experiment is claimed." }, "stability": { "value": "Stable", "trigger": "No specific verified pending result likely to reverse the clinical causal antecedent assessment was identified. Stable follows the framework definition and does not assert permanent completeness.", "justification": "No specific verified pending result likely to reverse the clinical causal antecedent assessment was identified. Stable follows the framework definition and does not assert permanent completeness." }, "divergence": { "implied_level": "Θ", "implied_level_basis": "Reviewer mapping of primary clinical trial framing: virus-directed intervention consistently changes clinical HIV disease and acquisition, without a claim that every infection is sufficient for AIDS. The published trials do not literally report an HSEF grade.", "assessed_level": "Θ", "gap_in_rungs": 0, "value": "Aligned", "justification": "Field framing mapped to Θ; assessed Θ; signed gap 0, Aligned. This is an explicit interpretation of clinical author conclusions, not a claim of a measured HSEF field vote." }, "calibration_note": "M/S/D never modify HSEF level or confidence." }, "change_record": { "applies": false, "prior_level": "Θ", "prior_confidence": null, "prior_source": null, "derived_before_consulting_prior": false, "new_level": "Θ", "direction": "newly assigned", "what_moved_it": "Existing HIV draft carried forward after a source-based checkpoint and Consensus cross-check. Grade unchanged; source-access and citation-context metadata updated. Not a new independent or blinded calibration.", "divergence_from_other_reviewers": null }, "proposed_decisive_experiments": [ { "name": "Registered boundary experiment", "experiment": "A stronger necessity-and-sufficiency assessment would require a prospectively specified noncircular syndrome definition and independently verified naturally acquired HIV status, host modifiers, exposure history and longitudinal outcomes. Use ethically delivered target-engaged treatment and adjudicated natural-course/clinical-care observations; do not induce infection or withhold effective therapy. The purpose is causal scope discrimination rather than recreating established treatment harm.", "readout": "Predetermined clinical immune-deficiency trajectory, verified viral engagement and independently adjudicated opportunistic events", "critical_control": "Independent diagnostic confirmation, explicit non-HIV phenocopy comparator, blinded clinical adjudication and prespecified host/timing scope", "supporting_result": "Prospectively correct cause-specific prediction and target-dependent trajectory alteration across the predetermined scope", "falsifying_result": "Repeated independently verified HIV-negative cases meeting a genuinely same-cause noncircular syndrome definition, or engaged suppression without predicted causal alteration after accounting for established timing irreversibility" } ], "knowledge_gaps": [ { "name": "Gap 1", "statement": "A necessary antecedent is distinct from infection-alone sufficiency.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 2", "statement": "Specific host and coinfection mechanisms remain incompletely identified.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 3", "statement": "Which residual outcomes reflect irreversible injury, coinfection, treatment toxicity or ongoing viral biology?", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 4", "statement": "Phenotype similarity cannot establish etiologic identity.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 5", "statement": "Selected body access and unexamined linked correction details limit this review.", "relevance": "Limits mechanism identification or scope." } ], "review_metadata": { "review_date": "2026-10-11", "reviewer": "Codex", "evidence_base_note": "63 primary reports; literature cutoff 2026-10-09; source examination UTC date 2026-10-10; bounded critical review, not exhaustive systematic review.", "literature_tools_available": true, "literature_tools_note": "Life Sciences Literature PubMed/Entrez, separately logged public original-body retrieval, and Consensus Pro browser searches. Provider output retained as observed browser text with citation-link mappings, or as previously exported connector documents where present. AI synthesis is not primary full-text verification. Consensus retrieved/included counts are not examined-primary counts. One Scite call covered five anchors: provider tallies and outgoing reference contexts, not audited incoming contrasting statements. One SciSpace discovery call returned supplementary leads; none added to the primary count. No independent blinded review.", "skill_version": "5.3", "validator_run": "PASS: exact archived HSEF v5.3 validator, rerun after final sealing.", "validator_warnings_addressed": "No warnings.", "limits": "Bounded critical review; not an exhaustive systematic review, complete-paper audit, independent scientific peer review or blinded calibration. HIV is an existing draft carried forward after a source checkpoint." }, "is_calibration_entry": { "value": false, "entry_role": "not_calibration", "blind_graded": null, "completed_blinded_calibration": false, "expected_band_sealed_at": "", "target_sha256": "", "target_authorship": "not applicable", "target_author_saw_review": null, "future_run_status": "not prepared", "unblinded_reason": "Ranking categorical verdict and index guidance were visible. No completed blinded calibration claimed." }, "upper_ladder_check": { "final_level_below_zeta": false, "equivalents_considered": [ { "kind": "mendelian_randomization", "available": false, "why_not_sufficient": "Orthogonal temporality, randomized suppression and prevention, and host susceptibility support the assembled clinical causal inference. Single observational limitations are not reimposed on that set. Ω remains unearned: infection is not sufficient for AIDS independently of host, duration, treatment and competing outcomes." }, { "kind": "natural_experiment", "available": true, "why_not_sufficient": "Orthogonal temporality, randomized suppression and prevention, and host susceptibility support the assembled clinical causal inference. Single observational limitations are not reimposed on that set. Ω remains unearned: infection is not sufficient for AIDS independently of host, duration, treatment and competing outcomes." }, { "kind": "dose_response_across_populations", "available": false, "why_not_sufficient": "Orthogonal temporality, randomized suppression and prevention, and host susceptibility support the assembled clinical causal inference. Single observational limitations are not reimposed on that set. Ω remains unearned: infection is not sufficient for AIDS independently of host, duration, treatment and competing outcomes." }, { "kind": "withdrawal_rechallenge", "available": true, "why_not_sufficient": "Orthogonal temporality, randomized suppression and prevention, and host susceptibility support the assembled clinical causal inference. Single observational limitations are not reimposed on that set. Ω remains unearned: infection is not sufficient for AIDS independently of host, duration, treatment and competing outcomes." }, { "kind": "therapeutic_perturbation_hard_endpoint", "available": true, "why_not_sufficient": "Orthogonal temporality, randomized suppression and prevention, and host susceptibility support the assembled clinical causal inference. Single observational limitations are not reimposed on that set. Ω remains unearned: infection is not sufficient for AIDS independently of host, duration, treatment and competing outcomes." } ], "convergence_present": true, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 63, "claims_total": 67, "claims_verified": 67, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 63, "generated_by": "Codex; HSEF v5.3", "gate_passed": true }, "claims": [ { "id": "C1", "text": "Documented seroconversion precedes increasing viral load and CD4 decline in 46 untreated Indian participants. Two-year small cohort does not alone isolate HIV from host and setting modifiers.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 1 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C2", "text": "Historical untreated progression differs across candidate ART-initiation criteria. Prediction of historical progression is not a randomized comparison of the recommended thresholds.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 2 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C3", "text": "Early measured HIV-specific CD8 cytokine responses did not predict AIDS-free survival or CD4 decline. Null immune-marker prediction does not refute HIV causation; the immunologic assay is a proxy.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 3 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C4", "text": "HGV-positive infected hemophiliacs had higher CD4 counts and better AIDS-free survival after adjustment. Coinfection association with uncertain mechanism does not establish a required protective cause.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 4 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C5", "text": "Early viral RNA and CD4 counts predicted later phenotype evolution; selected receptor percentages did not. Correlated host and viral measurements do not identify an independently necessary receptor mechanism.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C6", "text": "Higher and unstable p24 predicted AIDS or death over 24 months in a 251-patient cohort. A prognostic biomarker is not a selective causal intervention; same cohort as PMID11109648.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 6 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C7", "text": "p24 and CD4 predicted three-year outcomes, with reported discrepancies against viral-load comparisons. Same 251-patient cohort as PMID10609356; discrepancies prevent treating all biomarkers as equivalent.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 7 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C8", "text": "Serially followed seronegative multitransfused hemophiliacs showed little evidence of silent infection. This bounds diagnostic failure in a selected exposed cohort; it is not a general absence-of-disease necessity experiment.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 8 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C9", "text": "Two higher-purity factor VIII cohorts had similar CD4 decline, survival and AIDS illness rates. Both cohorts were HIV infected and nonrandomized; no seronegative comparator and baseline CD4 differed.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 9 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C10", "text": "AIDS risk fell in the post-HAART hemophilia cohort while non-AIDS mortality rose. Historical periods differ in care, survival and liver disease; AIDS and all-cause mortality remain distinct.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 10 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C11", "text": "Italian infected hemophiliacs developed AIDS after estimated seroconversion, with age and treatment-associated heterogeneity. Estimated infection times and nonrandomized factor exposure leave confounding.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 11 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C12", "text": "CCR5 deletion genotypes were associated with lower acquisition risk in high-risk seronegative cohorts. Genotype associations and exposure reporting do not prove absolute resistance or suffice as AIDS-necessity evidence alone.", "carries_number": true, "load_bearing_for": [ "SC3" ], "source_ns": [ 12 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C13", "text": "Some long-term nonprogressors lost CD4 stability with detectable viremia, while others remained controlled. Selected survivors and small samples do not establish inevitable progression or a universal protective mechanism.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 13 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C14", "text": "HLA alleles associated with opposite AIDS progression patterns among selected extreme progressors. Extreme selection, ancestry and multiple allele tests limit causal attribution and generalization.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C15", "text": "A host regulatory genotype associated with higher perinatal acquisition in untreated mother-infant pairs. Ethnic frequency and subgroup associations do not establish necessity or individual infection certainty.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 15 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C16", "text": "Selected receptor allele frequencies differed among infected, exposed seronegative and healthy Colombian groups. Small observational comparisons and multiple variants require replication; no homozygous deletion was found.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 16 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C17", "text": "Thai exposed seronegative women did not show significant overall haplogroup differences from comparison groups. Very small groups and a suggested two-person pattern do not validate a protective causal instrument.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 17 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C18", "text": "Deletion heterozygotes had lower viral setpoints and slower CD4 deterioration, but an infected homozygote progressed rapidly. Host protection is incomplete; rare homozygote infection contradicts an absolute genotype barrier, not HIV causation.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 18 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C19", "text": "A deletion genotype was enriched among exposed uninfected people in a documented local outbreak. Small observational exposure contrasts with population controls leave ancestry and exposure-dose confounding.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 19 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C20", "text": "CCR5 variants differed between HIV-positive adults and neonatal population controls. Different-age and exposure-unmatched controls cannot establish a clean resistance natural experiment.", "carries_number": true, "load_bearing_for": [ "SC3" ], "source_ns": [ 20 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C21", "text": "Tested HLA and KIR configurations did not explain resistance in exposed uninfected hemophiliacs. Negative selected genetic associations do not refute HIV causation or rule out other protective pathways.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 21 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C22", "text": "Deletion heterozygosity was more frequent in a small exposed seronegative Italian group. Small selected observational cohorts and self-reported exposure restrict instrument validity.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 22 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C23", "text": "Tested variants were not significantly associated with resistance in exposed North Indian partners. Small sample and an unexamined linked erratum limit inference; null variants are not proof that host factors never matter.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 23 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C24", "text": "Immediate ART improved CD4 counts and reduced D-dimer relative to deferred treatment, with other inflammatory markers null. SMART secondary biomarker report is not independent clinical replication and biomarkers alone do not prove AIDS prevention.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 24 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C25", "text": "SMART baseline untreated subgroup had more clinical events under the deferral strategy. Secondary subgroup and wide intervals; grouped with SMART, not an independent randomization.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 25 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C26", "text": "Prior opportunistic infections predicted later infections even after CD4 adjustment in two clinical-trial cohorts. Within-infection prognosis is not direct HIV acquisition causality; parent cohorts may overlap other ART reports.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 26 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C27", "text": "Age, CD4, first AIDS condition and function predicted survival among veterans developing AIDS. Secondary clinical-staging analysis is not an independent intervention test.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 27 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C28", "text": "Zidovudine-treated Danish patients showed CD4 and antigen changes and better mortality than historical controls, with toxicity. Historical comparison cannot isolate drug effect from care and selection; no randomized untreated comparator.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 28 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C29", "text": "PROMISE ART reduced early infant infection relative to zidovudine alone, while adverse maternal and neonatal outcomes differed. Active comparators and competing toxicity prevent interpreting HIV-free survival as proof of universal harmlessness or AIDS sufficiency.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 29 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C30", "text": "Randomized earlier ART in Haiti reduced deaths and incident tuberculosis compared with later initiation. A specific baseline CD4 and care setting; treatment benefit does not imply every infected person necessarily progresses.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 30 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C31", "text": "Randomized Delta regimens produced differing RNA suppression; attained RNA nadir predicted subsequent survival. Within-trial mediator association is not randomized viral-load assignment; an extended report shares parent randomization.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 31 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C32", "text": "Immediate ART did not improve mortality or AIDS-event/death timing in HIV-associated tuberculous meningitis and increased grade-four harms. A timing contrast in severe CNS infection does not test eliminating HIV versus persistent infection or refute its causal antecedence.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 32 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C33", "text": "Double-blind high- versus low-dose zidovudine in children showed no efficacy or tolerance difference. Two active regimens do not establish efficacy against no treatment or monotonic benefit from greater dosage.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 33 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C34", "text": "Lower-dose zidovudine improved survival versus the standard dose and reduced selected toxicities, without changing OI timing. Active-dose comparison separates dose toxicity from virus causation and does not supply independent untreated counterfactual.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 34 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C35", "text": "A small short-cycle interruption trial maintained CD4 above its primary threshold with few virologic failures and no deaths. Only 35 randomized people and brief follow-up; not the same interruption strategy or endpoint as SMART.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 35 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C36", "text": "High HBV replication predicted mortality despite early ART, without interaction by ART strategy. TEMPRANO secondary cohort; coinfection mortality is not equivalent to HIV-independent AIDS.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 36 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C37", "text": "Extended infant antiretroviral prophylaxis reduced postnatal HIV acquisition relative to the control strategy. Acquisition rather than AIDS is the endpoint; a linked correction is retained and its details were not examined.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 37 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C38", "text": "Among twelve infected infants, prior prophylaxis exposure associated with more early symptoms and higher viral measurements. Conditioning on breakthrough infection and tiny samples creates selection bias; this does not estimate prophylaxis harm across all randomized infants.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 38 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C39", "text": "Two active infant prophylaxis regimens had similar low acquisition rates, without superiority of one. No placebo/no-prophylaxis arm; a linked correction was not examined and absolute causal prevention cannot be estimated from this comparison alone.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 39 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C40", "text": "California hemophilia surveillance documented HIV prevalence and age-associated cumulative AIDS after infection. Serologic status was known in only part of the clinic population and no uninfected clinical counterfactual was reported in the examined passage.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 40 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C41", "text": "Known-date French infection cohorts had longer estimated time to AIDS across increasingly potent treatment eras. Calendar and treatment selection confounding remain; model-estimated incubation is not observed universal lifespan.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 41 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C42", "text": "Earlier CD4 slope predicted subsequent AIDS beyond latest count in seroconversion cohorts. Prediction of disease trajectory does not itself manipulate the upstream virus.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 42 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C43", "text": "Older infected hemophiliacs progressed faster after seroconversion, including after CD4 adjustment. Age and care confounding remain; heterogeneity rejects a single inevitable timetable.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 43 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C44", "text": "Schistosome coinfection associated with slower adverse HIV outcomes, opposite the authors' original hypothesis. Observational competing-risk analysis and immune modifiers are not evidence of AIDS without HIV.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 44 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C45", "text": "Baseline viral phenotype predicted CD4 decline and clinical AIDS progression beyond selected covariates. Phenotype is observational; a linked erratum was not examined and no operational assay inference is needed.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 45 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C46", "text": "Non-HIV idiopathic CD4 lymphocytopenia caused persistent low counts and opportunistic illnesses, including some AIDS-defining clinical conditions. This refutes equating every AIDS-like clinical condition with HIV; a different syndrome is not direct refutation of HIV-associated AIDS causation. Linked correction is an author-name correction.", "carries_number": true, "load_bearing_for": [ "SC3" ], "source_ns": [ 46 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C47", "text": "A French ICL cohort showed heterogeneous immune deficiencies, opportunistic disease and deaths without HIV. The generic low-CD4/OI phenotype has other causes; necessity must be evaluated for the HIV-associated syndrome rather than every immune-deficiency phenotype.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 47 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C48", "text": "Prospective ICL referral patients often had autoimmune features and altered immune-cell distributions. Referral selection and unclear initiating mechanism prevent proving a competing universal cause of AIDS.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 48 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C49", "text": "Persistent and transient elite controllers differed in observed reservoir landscape before control loss. Selected infected controllers show modification of course; reservoir comparisons alone do not prove a sufficient protective mechanism.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 49 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C50", "text": "Protective host alleles collectively associated with nonprogression, with prominent HLA effects. Small selected genetic combinations and additive associations do not establish absolute protection or independence from infection.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 50 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C51", "text": "START immediate treatment reduced the primary clinical composite and serious AIDS events with improved CD4 trajectory and viral suppression. Open-label strategy but blinded event review; interim stopping, residual events and nonsignificant all-cause mortality are retained. It does not prove infection-alone sufficiency.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 51 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 0:METHODS:paragraph4, 0:METHODS:paragraph5, 0:METHODS:paragraph8, 1:RESULTS:paragraph4, 1:RESULTS:paragraph5, 1:RESULTS:paragraph6, 1:RESULTS:paragraph8. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C52", "text": "SMART CD4-guided episodic ART increased opportunistic disease/death versus continuous suppression; rising RNA and falling CD4 aligned with harm. Specific interruption strategy and previously treated population; mediator adjustment is not perfect causal mediation and toxicity/coinfections still matter.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 52 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C53", "text": "TEMPRANO early ART and tuberculosis preventive treatment independently reduced severe clinical illness or death. Combined clinical composite and setting-specific coinfection prevention; ART and IPT are separate interventions, not proof that all mortality is HIV alone.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 53 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C54", "text": "Double-blind AZT versus placebo reduced deaths and opportunistic infections over short follow-up with improved function. Selected advanced disease, early termination and drug toxicity limit magnitude and long-term inference; one drug alone does not settle mechanism specificity.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 54 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C55", "text": "Baseline plasma RNA predicted AIDS and death over long follow-up in 180 infected men beyond CD4 prognostic value. Primary cohort despite a Comment indexing tag; observation alone does not establish causation and a linked erratum was not examined.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 55 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C56", "text": "iPrEx prophylaxis reduced new HIV acquisition versus placebo; measured exposure correlated with protection. Acquisition not AIDS is the randomized endpoint; postrandomization measured exposure association is not independently randomized adherence.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 56 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C57", "text": "Partners PrEP active regimens reduced HIV acquisition versus placebo in serodiscordant couples. The pathway endpoint is infection incidence, not ultimate AIDS necessity or sufficiency; adherence and context matter.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 57 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C58", "text": "HPTN052 early treatment reduced linked partner acquisition and clinical events. Transmission and clinical follow-up share the same randomization as PMID24602844 and cannot be counted as separate causal lines.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 58 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C59", "text": "Randomized maternal/infant zidovudine reduced infant acquisition versus placebo. An acquisition-prevention link complements progression trials but alone does not prove downstream AIDS inevitability or drug harmlessness.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 59 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C60", "text": "CHER earlier infant ART reduced mortality and serious clinical progression with improved CD4 percentages. Infant baseline eligibility, limited early follow-up and reassessment after stopping restrict extrapolation; no infection-alone sufficiency proof.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 60 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph4, 1:Results:paragraph6, 1:Results:paragraph7. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C61", "text": "HPTN052 follow-up reduced first AIDS events, while the primary clinical composite and mortality comparisons were not significant. Same parent trial as PMID21767103; significant secondary outcomes must not be substituted for a positive primary composite.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 61 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 2:Results:paragraph1, 2:Results:paragraph2, 2:Results:paragraph4. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C62", "text": "Pooled individual seroconverter trajectories showed CD4 deterioration and mortality varying by age and region. Primary participant-data analysis shares contributing cohorts; modeled untreated survival and informative ART initiation are limitations.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 62 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C63", "text": "Most selected long-term nonprogressors later lost status, with lower CD4 or higher RNA predicting loss. Nonprogression requires untreated status and CD4 at least 500 as well as absence of AIDS; its percentages are not simply AIDS-free survival probabilities. CASCADE overlaps other cohort analyses.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 63 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "CSC1", "text": "Documented seroconversion precedes immune deterioration across clinical exposure settings. This observational chain is interpreted together with randomized viral suppression and clinical rescue; it is not made causal by prognostic RNA correlations alone.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14, 18, 26, 27, 36, 38, 40, 41, 42, 43, 44, 45, 49, 50, 55, 62, 63 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-10", "note": "" }, { "id": "CSC2", "text": "Earlier sustained ART improves CD4 and clinical outcomes, while interruption harms selected populations. Broad predictive consistency survives known timing and toxicity limits. Clinical suppression benefit is not infection-alone sufficiency.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 24, 25, 28, 30, 31, 32, 33, 34, 35, 51, 52, 53, 54, 58, 60, 61 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-10", "note": "" }, { "id": "CSC3", "text": "HIV is a necessary causal antecedent of the HIV-associated AIDS process under the registered clinical distinction, supported by convergent acquisition, temporality and suppression evidence rather than classification alone. Generic immunodeficiency has other causes. Host controllers and treatment change progression without removing the viral antecedent. Necessity does not imply inevitable AIDS.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 1, 4, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 25, 29, 30, 32, 36, 37, 38, 39, 40, 41, 43, 44, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-10", "note": "" }, { "id": "CH", "text": "HIV is a well-supported causal antecedent of HIV-associated AIDS; infection does not guarantee progression, and other illnesses can cause similar immune deficiency.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 51, 52, 60, 46, 63 ], "verification": "verified", "verified_against": "Bounded synthesis of examined sources; score is adjudication.", "verified_on": "2026-10-10", "note": "" } ], "citation_ledger": [ { "n": 1, "citation": "Mehendale SM, Bollinger RC, Kulkarni SS et al. Rapid disease progression in human immunodeficiency virus type 1-infected seroconverters in India. AIDS research and human retroviruses. 2002.", "tier": "A", "kind": "primary", "pmid": "12487823", "doi": "10.1089/08892220260387913", "url": "https://pubmed.ncbi.nlm.nih.gov/12487823/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID12487823", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C1", "CSC1", "CSC3" ] }, { "n": 2, "citation": "Ioannidis JP, O'Brien TR, Goedert JJ. Evaluation of guidelines for initiation of highly active antiretroviral therapy in a longitudinal cohort of HIV-infected individuals. AIDS (London, England). 1998.", "tier": "A", "kind": "primary", "pmid": "9875579", "doi": "10.1097/00002030-199818000-00010", "url": "https://pubmed.ncbi.nlm.nih.gov/9875579/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID9875579", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C2", "CSC1" ] }, { "n": 3, "citation": "Schellens IM, Borghans JA, Jansen CA et al. Abundance of early functional HIV-specific CD8+ T cells does not predict AIDS-free survival time. PloS one. 2008.", "tier": "A", "kind": "primary", "pmid": "18648514", "doi": "10.1371/journal.pone.0002745", "url": "https://pubmed.ncbi.nlm.nih.gov/18648514/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID18648514", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C3", "CSC1" ] }, { "n": 4, "citation": "Yeo AE, Matsumoto A, Hisada M et al. Effect of hepatitis G virus infection on progression of HIV infection in patients with hemophilia. Multicenter Hemophilia Cohort Study. Annals of internal medicine. 2000.", "tier": "A", "kind": "primary", "pmid": "10858179", "doi": "10.7326/0003-4819-132-12-200006200-00006", "url": "https://pubmed.ncbi.nlm.nih.gov/10858179/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID10858179", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C4", "CSC1", "CSC3" ] }, { "n": 5, "citation": "van Rij RP, Hazenberg MD, van Benthem BH et al. Early viral load and CD4+ T cell count, but not percentage of CCR5+ or CXCR4+ CD4+ T cells, are associated with R5-to-X4 HIV type 1 virus evolution. AIDS research and human retroviruses. 2003.", "tier": "A", "kind": "primary", "pmid": "12803997", "doi": "10.1089/088922203765551737", "url": "https://pubmed.ncbi.nlm.nih.gov/12803997/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID12803997", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C5", "CSC1" ] }, { "n": 6, "citation": "Rubio Caballero M, Nogués Biau A, Falguera Sacrest M et al. [The prognostic markers of HIV infection progression. A study of the p24 antigen in a cohort of 251 patients]. Anales de medicina interna (Madrid, Spain : 1984). 1999.", "tier": "A", "kind": "primary", "pmid": "10609356", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/10609356/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "SPANISH_251", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C6", "CSC1" ] }, { "n": 7, "citation": "Rubio Caballero M, Nogués Biau A, Falguera Sacrest M et al. [The prognostic markers of survival and progression in HIV-1 infection. A study of CD4+ lymphocytes, antigen p24 and viral load during 3 years in a cohort of 251 patients]. Anales de medicina interna (Madrid, Spain : 1984). 2000.", "tier": "A", "kind": "primary", "pmid": "11109648", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/11109648/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "SPANISH_251", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C7", "CSC1" ] }, { "n": 8, "citation": "Gibbons J, Cory JM, Hewlett IK et al. Silent infections with human immunodeficiency virus type 1 are highly unlikely in multitransfused seronegative hemophiliacs. Blood. 1990.", "tier": "A", "kind": "primary", "pmid": "2242420", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/2242420/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID2242420", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C8", "CSC1", "CSC3" ] }, { "n": 9, "citation": "Hay CR, Ludlam CA, Lowe GD et al. The effect of monoclonal or ion-exchange purified factor VIII concentrate on HIV disease progression: a prospective cohort comparison. British journal of haematology. 1998.", "tier": "A", "kind": "primary", "pmid": "9674733", "doi": "10.1046/j.1365-2141.1998.00753.x", "url": "https://pubmed.ncbi.nlm.nih.gov/9674733/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID9674733", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C9", "CSC1", "CSC3" ] }, { "n": 10, "citation": "Katsarou O, Touloumi G, Antoniou A et al. Progression of HIV infection in the post-HAART era among a cohort of HIV+ Greek haemophilia patients. Haemophilia : the official journal of the World Federation of Hemophilia. 2005.", "tier": "A", "kind": "primary", "pmid": "16011588", "doi": "10.1111/j.1365-2516.2005.01109.x", "url": "https://pubmed.ncbi.nlm.nih.gov/16011588/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID16011588", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C10", "CSC1", "CSC3" ] }, { "n": 11, "citation": "Schinaia N, Ghirardini AM, Mazzucconi MG et al. Clinical factors associated with progression to AIDS in the Italian cohort of HIV-positive hemophiliacs. G.I.C.C. Gruppo Italiano Coagulopatie Congenite. Thrombosis and haemostasis. 1994.", "tier": "A", "kind": "primary", "pmid": "7974372", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7974372/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID7974372", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C11", "CSC1", "CSC3" ] }, { "n": 12, "citation": "Marmor M, Sheppard HW, Donnell D et al. Homozygous and heterozygous CCR5-Delta32 genotypes are associated with resistance to HIV infection. Journal of acquired immune deficiency syndromes (1999). 2001.", "tier": "A", "kind": "primary", "pmid": "11511825", "doi": "10.1097/00126334-200108150-00009", "url": "https://pubmed.ncbi.nlm.nih.gov/11511825/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID11511825", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C12", "CSC3" ] }, { "n": 13, "citation": "Rodés B, Toro C, Paxinos E et al. Differences in disease progression in a cohort of long-term non-progressors after more than 16 years of HIV-1 infection. AIDS (London, England). 2004.", "tier": "A", "kind": "primary", "pmid": "15166526", "doi": "10.1097/00002030-200405210-00004", "url": "https://pubmed.ncbi.nlm.nih.gov/15166526/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID15166526", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C13", "CSC1", "CSC3" ] }, { "n": 14, "citation": "Hendel H, Caillat-Zucman S, Lebuanec H et al. New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS. Journal of immunology (Baltimore, Md. : 1950). 1999.", "tier": "A", "kind": "primary", "pmid": "10352317", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/10352317/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID10352317", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C14", "CSC1", "CSC3" ] }, { "n": 15, "citation": "Kostrikis LG, Neumann AU, Thomson B et al. A polymorphism in the regulatory region of the CC-chemokine receptor 5 gene influences perinatal transmission of human immunodeficiency virus type 1 to African-American infants. Journal of virology. 1999.", "tier": "A", "kind": "primary", "pmid": "10559343", "doi": "10.1128/JVI.73.12.10264-10271.1999", "url": "https://pubmed.ncbi.nlm.nih.gov/10559343/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID10559343", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C15", "CSC3" ] }, { "n": 16, "citation": "Zapata W, Aguilar-Jiménez W, Pineda-Trujillo N et al. Influence of CCR5 and CCR2 genetic variants in the resistance/susceptibility to HIV in serodiscordant couples from Colombia. 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The Journal of infectious diseases. 1996.", "tier": "A", "kind": "rct", "pmid": "8627060", "doi": "10.1093/infdis/173.5.1097", "url": "https://pubmed.ncbi.nlm.nih.gov/8627060/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID8627060", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C33", "CSC2" ] }, { "n": 34, "citation": "Fischl MA, Parker CB, Pettinelli C et al. A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group. 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Infectious diseases. 2014.", "tier": "A", "kind": "rct", "pmid": "24602844", "doi": "10.1016/S1473-3099(13)70692-3", "url": "https://pubmed.ncbi.nlm.nih.gov/24602844/", "status_flags": [ "ErratumIn: PMID not supplied" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "HPTN052", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 2:Results:paragraph1, 2:Results:paragraph2, 2:Results:paragraph4. No complete-paper or supplement audit claimed.", "carries_claims": [ "C61", "CSC2", "CSC3" ] }, { "n": 62, "citation": "Mangal TD, UNAIDS Working Group on CD4 Progression and Mortality Amongst HIV Seroconverters including the CASCADE Collaboration in EuroCoord. Joint estimation of CD4+ cell progression and survival in untreated individuals with HIV-1 infection. AIDS (London, England). 2017.", "tier": "A", "kind": "primary", "pmid": "28301424", "doi": "10.1097/QAD.0000000000001437", "url": "https://pubmed.ncbi.nlm.nih.gov/28301424/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "CASCADE_POOLED", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C62", "CSC1", "CSC3" ] }, { "n": 63, "citation": "van der Helm JJ, Geskus R, Lodi S et al. Characterisation of long-term non-progression of HIV-1 infection after seroconversion: a cohort study. The lancet. 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No complete-paper or supplement audit claimed.", "carries_claims": [ "C63", "CSC1", "CSC3", "CH" ] } ], "independence_basis": { "required": true, "lines": [ { "label": "Prospective acquisition-to-deterioration chronology", "sources": [ 1 ], "excludes_error": "Excludes purely reverse-temporal HIV measurement after AIDS onset; does not alone exclude all exposure or host confounding." }, { "label": "Randomized targeted suppression and withdrawal", "sources": [ 51, 52, 60 ], "excludes_error": "Reduces treatment-selection, behavioral exposure and retrospective chronology errors; blinded START event review reduces outcome-adjudication bias. Shared viral-treatment off-target or care effects are considered explicitly." }, { "label": "Randomized prevention of acquisition", "sources": [ 57, 59 ], "excludes_error": "Tests incident agent acquisition rather than symptom improvement, opposing a downstream marker-only interpretation. 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This controlled perturbation carries stronger causal weight than correlation alone.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/17135583/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_06_10_2026-10-09\\hiv-aids\\examinations\\results-48-63.json" ], "body_receipts": [] }, { "pmid": "24602844", "doi": "10.1016/S1473-3099(13)70692-3", "source_type": "primary study report", "study_group": "HPTN052", "access_depth": "full_text_partial", "consensus_aspect": "HPTN 052 supports earlier treatment.", "result_comparison": "Original clinical follow-up abstract retains the nonsignificant primary composite (p=.074) while noting the positive AIDS-event comparison (p=.031). 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