Emerging HIV drug resistance in sub-Saharan Africa Effects on treatment outcomes

The massive roll out of ART in sub-Saharan Africa since 2004 has inevitably been accompanied by the emergence of acquired HIV drug resistance (HIVDR) in treated individuals and transmitted HIVDR in newly infected individuals. To develop a public health framework to monitor and prevent the emergence of HIVDR to maximize long-term ART effectiveness, the ‘Pan African Studies to Evaluate Resistance’ (PASER) program was established in six African countries from 2006. Later, the Monitoring Antiretroviral Resistance in the African Children (MARCH) pediatric cohort was initiated in Uganda from 2010 with similar objectives to PASER study to address HIV drug resistance a problem to which children are especially vulnerable. With an expanding number of people developing failure and requiring second-line therapy, there was need to develop the evidence base for second- line therapy in Africa. In the context of extensive resistance at the time of first-line failure due to limited access to viral load monitoring, program challenges and resource limitations, a single uniform second- line treatment was likely to be the only feasible management approach. The Europe-Africa Research Network for Evaluation of Second-line Therapy (EARNEST) randomized clinical trial was conducted in 5 African countries from 2010 to provide the necessary evidence to inform second line therapy choices in a way that was relevant and appropriate to the public health approach to HIV treatment rollout. This thesis presents the results from these three prospective cohort studies, assessing the emergence of pretreatment and acquired HIVDR and its impact on first-line and second-line treatment outcomes.