Title: HIV Treatment and Prevention in KwaZulu-Natal, South Africa
Description: In 2015, the World Health Organization (WHO) announced revised guidelines for the treatment of HIV, recommending immediate initiation of antiretroviral therapy (ART) for all HIV-infected individuals worldwide. This recommendation was based on the results of several landmark randomized controlled trials of immediate ART initiation that documented substantial decreases in HIV transmission within couples and improvements in clinical outcomes in individuals. However, the degree to which global scale-up of immediate ART initiation will result in reductions in HIV transmission and gains in life expectancy depends on real-world effectiveness. Outside of trials, a large proportion of HIV-infected individuals do not know their status and resource constraints can affect the supply of ART.

Using the Africa Centre for Population Health’s demographic and HIV surveillance program, a population-based open cohort that has been conducting annual surveillance since 2000, this dissertation evaluates the effectiveness of ART in a real-world setting at multiple levels, including for individuals, within couples, and in households. First, this dissertation analyzes the effect of ART uptake in serodiscordant couples in the risk of HIV acquisition by the uninfected partner. Second, the effectiveness of immediate eligibility for ART on household-level HIV acquisition is assessed. Finally, the effect of immediate ART eligibility and uptake on survival in HIV-infected individuals is examined using two causal modeling approaches.

ART was found to be highly effective at preventing new infections and reducing mortality in a hyperendemic region of rural KwaZulu-Natal. In serodiscordant couples, the use of ART was associated with a 77% reduction in HIV acquisition in this cohort, a dramatic decrease in HIV transmission despite the severe resource constraints of the area. As expected, the effect in households where not all members are sexual partners was less pronounced, with a 53% reduction in HIV transmission. Finally, the use of ART led to a 35-40% decrease in all-cause mortality. Taken together, these results indicate a strong protective effect of ART outside of a tightly controlled clinical trial setting. The scale-up of immediate ART eligibility and initiation in Sub-Saharan Africa likely will lead to significant reductions in the HIV epidemic and in the survival of HIV-infected individuals.