Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis - PubMed (original) (raw)
Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis
Deborah Donnell et al. Lancet. 2010.
Abstract
Background: 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.
Methods: 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 microL 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.
Findings: 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 microL. 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 microL. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count greater than 200 cells per microL, 66 (70%) of 94 transmissions occurred when plasma HIV-1 concentrations exceeded 50 000 copies per mL.
Interpretation: 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.
Funding: Bill & Melinda Gates Foundation; US National Institutes of Health.
Copyright 2010 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Conflict of Interest:
JM and CC received research grant support from GlaxoSmithKline, which did not include salary support, and JM has received speaker fees from Abbott Laboratories.
Comment in
- HIV drugs for treatment, and for prevention.
Dabis F, Newell ML, Hirschel B. Dabis F, et al. Lancet. 2010 Jun 12;375(9731):2056-7. doi: 10.1016/S0140-6736(10)60838-0. Epub 2010 May 26. Lancet. 2010. PMID: 20537377 No abstract available.
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References
- Quinn TC, Wawer MJ, Sewankambo N, et al. Rakai Project Study Group. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med. 2000 Mar 30;342(13):921–929. - PubMed
- Chaisson RE, Keruly JC, Moore RD. Association of initial CD4 cell count and viral load with response to highly active antiretroviral therapy. JAMA. 2000 Dec 27;284(24):3128–3129. - PubMed
- Phillips AN, Staszewski S, Weber R, et al. HIV viral load response to antiretroviral therapy according to the baseline CD4 cell count and viral load. JAMA. 2001 Nov 28;286(20):2560–2567. - PubMed
- Graham SM, Holte SE, Peshu NM, et al. Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding. AIDS. 2007 Feb 19;21(4):501–507. - PubMed
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