Fast track — ArticlesHeterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis
Introduction
The quantity of HIV-1 in plasma is a primary determinant of the risk of HIV-1 transmission.1 Antiretroviral therapy (ART) reduces plasma HIV-1 to undetectable concentrations within 6 months of initiation in most patients,2, 3 and seminal and cervicovaginal HIV-1 concentrations are also reduced to undetectable levels in most people on ART.4, 5, 6, 7 Use of peripartum ART has led to almost complete elimination of mother-to-child HIV-1 transmission in resource-rich settings.8 Substantial reduction in plasma and genital HIV-1 concentrations in patients initiating ART could greatly reduce risk of HIV-1 transmission to sexual partners.9 However, empirical data for the rate of sexual HIV-1 transmission from patients receiving ART are scarce. In a meta-analysis of data from five studies, some of which were unpublished, investigators reported only five cases of HIV-1 transmission from patients receiving ART to sexual partners during 1098 person-years of follow-up, which is consistent with an infection rate of 0·19–1·09 per 100 person-years.10 Few studies have compared sexual behaviour before and after ART initiation, which is an important behavioural consideration. Additionally, the relation between evolving HIV-1 treatment guidelines,11, 12 which recommend ART initiation at CD4 cell counts between 200 cells per μL and 350 cells per μL, and HIV-1 transmission risk is unknown. Demonstration of an HIV-1 transmission benefit for patients initiating ART at CD4 cell counts at or above present guidelines could provide impetus to provide ART to populations as a prevention strategy for HIV-1 (eg, the test and treat approach), in addition to clinical benefits.
The Partners in Prevention HSV/HIV Transmission Study enrolled participants co-infected with HIV-1 and herpes simplex virus type 2 (HSV-2), along with their HIV-1 seronegative heterosexual partners, in a randomised, double-blind, placebo-controlled, clinical trial13 of aciclovir HSV-2 suppressive therapy. As reported previously, aciclovir did not reduce HIV-1 transmission within the couples, although infected participants who were randomly allocated to aciclovir had a 73% reduction in incident genital ulcer disease due to HSV-2, an average 0·25 log10 copies per mL reduction in HIV-1 plasma concentration, and a 16% reduction in risk of HIV-1 disease progression.13, 14 We undertook a post-hoc analysis of data from this study, with the aim of assessing effect of ART use by HIV-1 infected participants on risk of HIV-1 transmission to their initially uninfected partners.
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Study design and participants
Participants in our prospective cohort analysis were from the Partners in Prevention HSV/HIV Transmission Study13 of aciclovir HSV-2 suppressive therapy versus placebo. Between November, 2004, and April, 2007, 3408 participants seropositive for HIV-1 and HSV-2 were enrolled, along with their HIV-1 seronegative heterosexual partners, from 14 sites in seven African countries (Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda, and Zambia). Couples were followed-up for up to 24 months, and
Results
3408 heterosexual HIV-1 serodiscordant couples were enrolled in the Partners in Prevention HSV/HIV Transmission Study. 27 couples for whom baseline serology did not confirm both HIV-1 and HSV-2 infection in the participants infected with HIV-1 were excluded. Table 1 shows baseline characteristics of the 3381 couples eligible for analysis. CD4 cell counts were lower (median 424 [334–571] vs 483 [355–664] cells per μL, p<0·0001) and plasma HIV-1 RNA concentrations were higher (median 4·3
Discussion
In this analysis of almost 3400 HIV-1 serodiscordant heterosexual couples from seven African countries, ART use by the infected person was accompanied by a 92% reduction in risk of HIV-1 transmission to their partner. An important strength of our study was phylogenetic linkage of HIV-1 transmissions within the study partnerships, which probably reduced misclassification of the source of transmission and improved precision of measurement of the effect of ART on HIV-1 risk. These observational
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