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Abstract
The expansion of combination antiretroviral therapy (cART) in resource-limited settings has led to improved survival but also the emergence of HIV drug resistance associated mutations (RAMs). As treatment strategies lean towards earlier cART initiation, it is expected that an increasing number of HIV-infected individuals will be exposed to cART for longer, potentially leading to higher prevalence of RAMs in both treatment naive, through transmitted RAMs, and treatment experienced individuals. This thesis aims to evaluate RAMs in recently infected individuals and those who have failed first-line cART in Asia. Additionally, adherence to cART, an important predictor of RAMs, was also investigated.
Analysis datasets were obtained from the TREAT Asia HIV databases. Firstly, the applications of different types of resistance interpretation systems on HIV-1 CRF01_AE were compared. Proportions of RAMs in recently-infected and treatment experienced individuals were then analysed, and the corresponding second-line virological outcome adjusting for adherence and genotypic susceptibility score were determined. Levels of suboptimal adherence utilising the self-reported questionnaire were evaluated. Additionally, the effects of unplanned treatment interruptions on treatment outcomes after cART resumption were investigated.
Although developed from subtype B, genotypic and virtual phenotypic resistance interpretation systems proved to be reliable in their predicted resistance calls for non-B subtypes, particularly CRF01_AE. RAMs in recently infected individuals were below 15%, however, multi-drug RAMs found in patients failing first-line cART existed in a high proportion but were not associated with second-line virological suppression. Adherence was the only factor showing a significant association, conferring the importance of high-level adherence beyond first-line therapy. Sites that assessed adherence more frequently, and longer time on cART, were associated with better adherence. Treatment interruptions due to adverse events did not have an effect on treatment response after cART had been resumed, possibly due to the shorter duration. Longer time off treatment was associated with higher hazard of treatment failure.
Continued monitoring of RAMs in recently infected and treatment experienced individuals in Asia should be encouraged. Greater emphasis on adherence counselling at the early stages of cART is beneficial in promoting treatment and program retention.