Identifying mechanisms behind HIV drug resistance in Sub-Saharan Africa: a systems approach

Abstract IntroductionHIV drug resistance (HIVDR) continues to threaten the effectiveness of worldwide antiretroviral therapy (ART). Emergence and transmission of HIVDR is driven by several interconnected factors. Though much has been done to uncover factors influencing HIVDR, overall interconnectedness between these factors remain unclear and African policy makers encounter difficulties setting priorities combating HIVDR. By employing a systems approach, involving multi-disciplinary HIVDR experts, we aimed to gain a deeper understanding of key determinants and their interactions driving HIVDR. MethodsWe designed a detailed system map of factors influencing HIVDR based on semi-structured interviews with 15 international HIVDR experts from or with experience in Sub-Saharan Africa. from different disciplinary backgrounds and institutions. The resulting detailed system map was conceptualized into three main HIVDR feedback loops and further strengthened with literature evidence.ResultsFactors influencing HIVDR in SSA and their interactions were sorted in five categories: biology, individual, social context, healthcare system and ‘overarching’. We identified three causal loops cross-cutting these layers, which relate to three interconnected subsystems of mechanisms influencing HIVDR. The ‘adherence motivation’ subsystem consists of opposite forces that ultimately create a balancing loop leading to a different set-point of adherence per individual which may vary over time. The ‘healthcare burden’ subsystem consists of a reinforcing loop leading to an increased HIVDR at local population level. The ‘ART overreliance’ subsystem is a balancing feedback loop leading to complacency among program managers when there is overreliance on ART with a perceived low risk to drug resistance. The three subsystems are interconnected at different levels. ConclusionsInterconnectedness of the three subsystems underlines the need to act on the entire system of factors surrounding HIVDR in Sub-Saharan Africa in order to target interventions and to prevent unwanted effects on other parts of the system.