HIV transmission in Discordant Couples in Africa in the context of ART availability

OBJECTIVE:This study aims to understand the basis of continued HIV-1 transmission in Zambian and Rwandan HIV-1 discordant couples in the context of ART. DESIGN:We identified 9 Zambian and 7 Rwandan acutely-infected, epidemiologically-linked couples from government CVCT clinics where transmitting partners reported being on ART near the time of transmission. METHODS:We quantified viral load (VL) and plasma antiretroviral (ARV) drug concentrations near the time of transmission and used these as surrogate measures for adherence. We also sequenced the polymerase gene from both donor and recipient partners to determine the presence of DR mutations (DRM). RESULTS:In Zambia, all transmitting partners had detectable VL and 8/9 were not on therapeutic ARV regimens. In the remaining couple, despite being on a therapeutic regimen, DRM were present and transmitted. In Rwanda, although 6/7 transmitting partners had detectable VL, therapeutic levels of ARV were detected in 4/7, but were accompanied by DRM. In the remaining 3 couples, either no ARV or sub-therapeutic regimens were detected. CONCLUSIONS:A reduction of ART effectiveness in non-trial settings was associated with lack of ARVs in plasma and detectable VL, as well as DR. In Zambia, where CVCT is not widely implemented, inconsistent adherence was high in couples unaware of their HIV discordance. In Rwanda, where CVCT is deployed country-wide, virologic failure was associated with DR and subsequent transmission. Together, these findings suggest that increasing ART availability in resource-limited settings without risk reduction strategies that promote adherence, may not be sufficient to control the HIV epidemic in the post-ART era.