Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples

Background Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Observational data, ecological studies and models suggest that sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). Objectives To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples. Search strategy We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. Selection criteria Randomised controlled trials, cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART Data collection and analysis Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 1814 references and examined 24 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. Main results One randomised controlled trial and seven observational studies were included in the review. These eight studies identified 464 episodes of HIV transmission, 72 among treated couples and 392 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350-550 cells/mu L. Similarly, the summary rate ratio for the seven observational studies was 0.34 [95% CI 0.13, 0.92], with substantial heterogeneity (I-2= 73%). After excluding two studies with inadequate person-time data, we estimated a summary rate ratio of 0.16 [95% CI 0.07, 0.35] with no noted heterogeneity (I-2= 0%). We also performed subgroup analyses among the observational studies to see if the effect of ART on prevention of HIV differed by the index partner's CD4 cell count. Among couples in which the infected partner had = 350 CD4 cells/mu L, we estimated a rate ratio of 0.02 [95% CI 0.00, 2.87]. In this subgroup, there were 61 transmissions in untreated couples and none in treated couples. Authors' conclusions ART is a potent intervention for prevention of HIV in discordant couples in which the index partner has = 550 CD4 cells/mu L. A new multicentre randomised controlled trial confirms the suspected benefit seen in earlier observational studies. Questions remain about durability of protection, the balance of benefits and adverse events associated with earlier therapy, long-termadherence and transmission of ART-resistant strains to partners. Resource limitations and implementation challenges must also be addressed. Counselling, support, and follow up, as well as mutual disclosure, may have a role in supporting adherence, so programmes should be designed with these components. In addition to ART provision, the operational aspects of delivering such programmes must be considered.