Thompson, Lindsay; (2018) Response to Antiretroviral Therapy in Adults and Children in Resource-limited Settings. Masters thesis (M.Phil), UCL (University College London).

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Abstract

The main aim of this thesis was to address outstanding questions in the treatment of adults and children in low/middle-income settings using data from the DART and ARROW trials. DART and ARROW both investigated whether delivery of ART in Africa with or without routine monitoring of CD4 counts led to similar outcomes in terms of efficacy. In addition ARROW investigated different numbers of drugs at ART initiation. Despite work already carried out on these data, many important clinical and epidemiological questions remained. I have investigated the patterns of mortality in DART and ARROW using flexible parametric models to assess the change in hazard of death over time, overall and for specific causes of death. Deaths were most commonly related to HIV disease both during the first year after ART initiation and subsequently. HIV-related deaths after 1 year on ART were also the main driver of long-term differences between CD4 vs. no-CD4 monitoring strategies. The contribution of HIV-related-malignancies, likely triggered by pre-cancerous events occurring before ART initiation, and longer-term ART mortality highlights the importance of earlier HIV diagnosis and access to care. Low but increasing risks of deaths from trauma/suicide in adults highlight the importance of long-term psychosocial support and empowering patients to manage their own treatment. Analysis comparing the DART STI/CT (structured treatment interruption/continuous therapy) randomised groups showed that interrupting ART is associated with lower CD4 counts and poorer clinical outcomes over the long-term even after returning to ART. These findings suggest that substantially greater efforts should be devoted to reducing the risk of any treatment interruption, including strengthening supply chain management, early contact of patients not attending drug refill visits and making short supplies of ART available for patients who travel.

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