| 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. |
