{
  "cutoff": "2026-10-09",
  "note": "Selected publication milestones, not an exhaustive history or priority-of-discovery determination.",
  "milestones": [
    {
      "year": "1987",
      "pmid": "3299089",
      "doi": "10.1056/NEJM198707233170401",
      "title": "The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.",
      "interpretation": "Placebo-controlled AZT trial measures short-term clinical outcomes.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/3299089/"
    },
    {
      "year": "1994",
      "pmid": "7935654",
      "doi": "10.1056/NEJM199411033311801",
      "title": "Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.",
      "interpretation": "Maternal and infant prophylaxis tests HIV acquisition.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/7935654/"
    },
    {
      "year": "1996",
      "pmid": "8638160",
      "doi": "10.1126/science.272.5265.1167",
      "title": "Prognosis in HIV-1 infection predicted by the quantity of virus in plasma.",
      "interpretation": "Plasma viral load predicts clinical prognosis observationally.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/8638160/"
    },
    {
      "year": "2006",
      "pmid": "17135583",
      "doi": "10.1056/NEJMoa062360",
      "title": "CD4+ count-guided interruption of antiretroviral treatment.",
      "interpretation": "SMART suppression/withdrawal design tests clinical disease modification.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/17135583/"
    },
    {
      "year": "2008",
      "pmid": "19020325",
      "doi": "10.1056/NEJMoa0800971",
      "title": "Early antiretroviral therapy and mortality among HIV-infected infants.",
      "interpretation": "CHER early infant treatment tests mortality and progression.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/19020325/"
    },
    {
      "year": "2011",
      "pmid": "21767103",
      "doi": "10.1056/NEJMoa1105243",
      "title": "Prevention of HIV-1 infection with early antiretroviral therapy.",
      "interpretation": "HPTN 052 treatment tests linked transmission and clinical outcomes.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/21767103/"
    },
    {
      "year": "2015",
      "pmid": "26192873",
      "doi": "10.1056/NEJMoa1506816",
      "title": "Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.",
      "interpretation": "START tests immediate treatment against deferred initiation.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/26192873/"
    }
  ],
  "gaps": [
    "A necessary antecedent is distinct from infection-alone sufficiency.",
    "Specific host and coinfection mechanisms remain incompletely identified.",
    "Which residual outcomes reflect irreversible injury, coinfection, treatment toxicity or ongoing viral biology?",
    "Phenotype similarity cannot establish etiologic identity.",
    "Selected body access and unexamined linked correction details limit this review."
  ],
  "decisive_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."
}