Antiretroviral Treatment as Prevention in African HIV-1 Serodiscordant Couples: Understanding the Challenges and Opportunities

The studies described in this dissertation examine the relationship between use of antiretroviral therapy (ART) and biologic and behavioral factors related to HIV-1 transmission risk in stable heterosexual HIV-1 serodiscordant African couples. ART is recommended for all HIV-1 infected persons, regardless of CD4 count, to reduce HIV-1 related morbidity, mortality and risk of transmission to uninfected partners. ART is a cornerstone of combination HIV-1 prevention, and optimizing use of ART, both for treatment and prevention, is an urgent public health priority. The complementary prospective studies presented in this dissertation were secondary analyses of data from the Partners PrEP Study, a randomized clinical trial of daily oral pre-exposure prophylaxis (PrEP) to decrease HIV-1 acquisition among HIV-1 uninfected members of serodiscordant couples in Kenya and Uganda. This work includes prospective studies of: 1) correlates of failure to achieve plasma viral suppression and virologic rebound after initial suppression, 2) frequency, magnitude and correlates of seminal HIV-1 RNA shedding in men initiating ART, 3) residual HIV-1 transmission risk during the first 6 months of ART, and 4) sexual risk behavior before and after ART. Younger age was associated with delayed ART initiation, failure to achieve viral suppression, and increased risk of virologic rebound after initial suppression. Seminal HIV-1 RNA shedding was infrequent and present at low levels in HIV-1 infected African men with suppressed blood HIV-1 RNA. There were no HIV-1 transmission events on suppressive ART. We observed residual HIV-1 transmission risk during the first 6-months of ART, prior to complete viral suppression in blood and genital secretions. Importantly, substantial risk compensation did not occur following ART initiation among HIV-1 infected persons with known uninfected partners. Results from this dissertation contribute further evidence of the effectiveness of ART for HIV-1 prevention, and provide reassurance that HIV-1 transmission risk declines after starting ART. As treatment guidelines evolve from wait-and-treat to test-and-treat, scaling up access to HIV-1 testing, improving linkage and retention in care, and achieving high ART coverage and complete viral suppression at individual and population levels are essential to achieving zero new HIV-1 infections and zero AIDS-related deaths.