Analysis of HIV virologic response-rebound data: prognostic indicators of post-HAART viral control

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The introduction of potent anti-retroviral therapy into standard clinical management of HIV infected individuals has been associated with high rates of reduction in plasma viral loads over short periods of time. However, there remains considerable variation in the degree of longer-term viral control as a result of viral resistance, toxicity, timing of treatment initiation and choice of drug regimen. In particular, the most appropriate time to initiate treatment remains clouded, with the need to initiate treatment sufficiently early in order to avoid irreversible damage balanced by the problems of potential viral resistance or toxicity if started too soon. Determination of factors which will assist practitioners to optimise the timing of treatment initiation remains a high priority. Our aim in this project is to develop and study the use of novel statistical mixed-effects models designed to analyse factors associated with visit-time viral load data following commencement of therapy, taking account of the entire follow-up profiles of responses over time. The project involves both theoretical and empirical analyses of the estimation and inferential properties of the mixed-model method in conjunction with comprehensive analyses of prognostic factors associated with post-treatment virologic control in patients from the Western Australian HIV Cohort Study. These include demographic, virologic, immunologic, adherence and host genetic factors. The statistical methods developed will have wide applicability and add significantly to the suite of procedures available for the analysis of longitudinal response data.