Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis
Deborah Donnell, Jared M Baeten, James Kiarie, Katherine K Thomas, Wendy Stevens, Craig R Cohen, James McIntyre, Jairam R Lingappa, Connie Celum, Partners in Prevention HSV/HIV Transmission Study Team, Connie Celum, Anna Wald, Jairam Lingappa, Jared M Baeten, Mary Campbell, Lawrence Corey, Robert W Coombs, James P Hughes, Amalia Magaret, M Juliana McElrath, Rhoda Morrow, James I Mullins, David Coetzee, Kenneth Fife, Edwin Were, Max Essex, Joseph Makhema, Elly Katabira, Allan Ronald, Susan Allen, Kayitesi Kayitenkore, Etienne Karita, Elizabeth Bukusi, Craig Cohen, Susan Allen, William Kanweka, Susan Allen, Bellington Vwalika, Saidi Kapiga, Rachel Manongi, Carey Farquhar, Grace John-Stewart, James Kiarie, Susan Allen, Mubiana Inambao, Sinead Delany-Moretlwe, Helen Rees, Guy de Bruyn, Glenda Gray, James McIntyre, Nelly Rwamba Mugo, Deborah Donnell, Jared M Baeten, James Kiarie, Katherine K Thomas, Wendy Stevens, Craig R Cohen, James McIntyre, Jairam R Lingappa, Connie Celum, Partners in Prevention HSV/HIV Transmission Study Team, Connie Celum, Anna Wald, Jairam Lingappa, Jared M Baeten, Mary Campbell, Lawrence Corey, Robert W Coombs, James P Hughes, Amalia Magaret, M Juliana McElrath, Rhoda Morrow, James I Mullins, David Coetzee, Kenneth Fife, Edwin Were, Max Essex, Joseph Makhema, Elly Katabira, Allan Ronald, Susan Allen, Kayitesi Kayitenkore, Etienne Karita, Elizabeth Bukusi, Craig Cohen, Susan Allen, William Kanweka, Susan Allen, Bellington Vwalika, Saidi Kapiga, Rachel Manongi, Carey Farquhar, Grace John-Stewart, James Kiarie, Susan Allen, Mubiana Inambao, Sinead Delany-Moretlwe, Helen Rees, Guy de Bruyn, Glenda Gray, James McIntyre, Nelly Rwamba Mugo
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.
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.
Copyright 2010 Elsevier Ltd. All rights reserved.
Source: PubMed