Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis

• Published in: The Lancet (British edition) Vol. 375; no. 9731; pp. 2092 - 2098
• Main Authors: Donnell, Deborah, Baeten, Jared M, Kiarie, James, Thomas, Katherine K, Stevens, Wendy, Cohen, Craig R, McIntyre, James, Lingappa, Jairam R, Celum, Connie
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 12.06.2010; Elsevier; Elsevier Limited
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; AIDS Serodiagnosis; Anti-Retroviral Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral agents; Antiretroviral drugs; Antiviral agents; Biological and medical sciences; CD4 Lymphocyte Count; Cohort Studies; Colleges & universities; Data collection; Disease; Female; General aspects; Herpesvirus 2, Human - isolation & purification; Heterosexuality; HIV; HIV Infections - drug therapy; HIV Infections - prevention & control; HIV Infections - transmission; HIV Infections - virology; HIV-1 - isolation & purification; Human immunodeficiency virus; Human immunodeficiency virus 1; Human subjects; Human viral diseases; Humans; Infectious diseases; Internal Medicine; Laboratories; Male; Medical research; Medical sciences; Pharmacology. Drug treatments; Plasma; Reproductive health; Risk assessment; RNA, Viral - blood; Sexual Partners; South African literature; Training Support; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Africa; Immunopathology; Antiretroviral agent; HIV-1 virus; Heterosexuality; Transmission; Retroviridae; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Medicine; Prospective; Chemotherapy; Treatment; Viral disease; Cohort study; Antiviral; Human immunodeficiency virus; Initiation; Public health
• ISSN: 0140-6736; 1474-547X; 1474-547X
• DOI: 10.1016/S0140-6736(10)60705-2

High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy (ART) reduces plasma HIV-1 concentrations. We aimed to assess the effect of ART use by patients infected with HIV-1 on risk of transmission to their uninfected partners. Participants in our prospective cohort analysis were from a randomised placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus type 2, and their HIV-1 seronegative partners. At enrolment, HIV-1 infected participants had CD4 counts of 250 cells per μL or greater and did not meet national guidelines for ART initiation; during 24 months of follow-up, CD4 counts were measured every 6 months and ART was initiated in accordance with national guidelines. Uninfected partners were tested for HIV-1 every 3 months. The primary outcome was genetically-linked HIV-1 transmission within the study partnership. We assessed rates of HIV-1 transmission by ART status of infected participants. 3381 couples were eligible for analysis. 349 (10%) participants with HIV-1 initiated ART during the study, at a median CD4 cell count of 198 (IQR 161–265) cells per μL. Only one of 103 genetically-linked HIV-1 transmissions was from an infected participant who had started ART, corresponding to transmission rates of 0·37 (95% CI 0·09–2·04) per 100 person-years in those who had initiated treatment and 2·24 (1·84–2·72) per 100 person-years in those who had not—a 92% reduction (adjusted incidence rate ratio 0·08, 95% CI 0·00–0·57, p=0·004). In participants not on ART, the highest HIV-1 transmission rate (8·79 per 100 person-years) was from those with CD4 cell counts lower than 200 cells per μL. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count greater than 200 cells per μL, 66 (70%) of 94 transmissions occurred when plasma HIV-1 concentrations exceeded 50 000 copies per mL. Low CD4 cell counts and high plasma HIV-1 concentrations might guide use of ART to achieve an HIV-1 prevention benefit. Provision of ART to HIV-1 infected patients could be an effective strategy to achieve population-level reductions in HIV-1 transmission. Bill & Melinda Gates Foundation; US National Institutes of Health.