BackgroundWhile research has identified many associations between socioeconomic factors and human immunodeficiency virus (HIV) nonsuppression, few qualitative studies have defined the mechanisms by which these factors interrelate and lead to HIV nonsuppression. The development of interventions to achieve universal virologic suppression and eliminate transmission will require a deeper understanding of the individual and social processes that drive antiretroviral therapy (ART) nonadherence and consequent viral nonsuppression.MethodsWe used a semistructured interview-based case-study approach to characterize changes across 3 time points in the lived contexts of 11 adolescents and young adults (aged 15-24 years) from intervention and control arms of a longitudinal HIV intervention trial in rural Kenyan and Ugandan communities. We sought to determine commonalities among those who never virally suppressed, those who became nonsuppressed, and those who moved from nonsuppression to viral suppression, exploring social and behavioral micro-processes or causal chains observed among individuals who share these trajectories.ResultsWe found that supportive family environments, high-quality service provision, and residential and partnership stability free of violence, or that permitted freedom to move and maintain extensive social ties both inside and outside one's immediate community, enabled ART adherence. We also found that several factors combine to have effects beyond each individual factor taken singly, for example, medication side effects were influenced by food insecurity; disclosure was most effective with individuals around whom one may potentially take medication, such as co-resident partners; and mobility compromised adherence when patients did not know how or where to access care in new places.RecommendationsOur findings suggest that to improve virologic suppression, clinical care and interventions should include assessment and strategies to address food insecurity, ART disclosure, and home-based violence from intimate partners or other family members. When such factors are present, we suggest referral for services, including violence prevention and protection services, and food provision for those patients who do not adhere because of medication side effects amplified by lack of food. We further recommend that clinics coordinate regionally to anticipate mobility, facilitate transfer of care to other areas, and ensure clients have access to information about care clinics elsewhere in the region.