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 23 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. MAIN
RESULTS: Seven observational studies and no randomised controlled trials were included in the review. These seven studies identified 436 episodes of HIV transmisison, 71 among treated couples and 365 among untreated couples. The summary rate ratio for all seven 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 found 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 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/µL, 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 appears to be a potent intervention for prevention of HIV in discordant couples. However, the most important question from a clinical standpoint is whether being in a serodiscordant sexual relationship and having >350 CD4 cells/µL should be an indication for ART. In our analysis, there were broad confidence intervals in this subgroup, overlapping the null hypothesis of no effect. There is currently one large randomised controlled trial in the field, whose results are scheduled to be ready in 2015. Significant questions remain about durability of protection, when to start treating an infected partner (for instance, at diagnosis or at a specific CD4 level) and transmission of ART-resistant strains to partners.