Grant: Doctoral Research Award - PA: Drug Safety and Effectiveness

Combination antiretroviral therapy (ART) has increased life expectancy for people living with HIV. Current guidelines recommend a combination of two backbone agents and a potent third agent of which a variety of choices exist. However, their comparative effectiveness, in particular safety outcomes and longer-term effectiveness, is not well understood and has yet to be examined within a single analysis. Network meta-analyses (NMAs) combine evidence from all available randomized clinical trials (RCTs) having compared any treatment of interest to common comparator. By evaluating the network of evidence, NMAs allow for strong inferences about comparative effectiveness between all interventions. The objective of my proposed doctoral research program is to utilize NMAs to assess the relative efficacy and safety of newer antiretroviral agents for the treatment drug-naive patients; to ensure these findings are translated to the appropriate agencies involved in developing guidelines and to ART patients. My program consists of three components: 1) Develop new methods that incorporate different study designs within NMAs. NMAs have traditionally been restricted to RCTs, overlooking important sources of evidence, particularly on safety outcomes where less evidence is sought; 2) Building on my methodological work, I will conduct a comprehensive NMA accounting for the factors that are likely to influence efficacy and safety of ART in drug-naive patients. Where possible, patient characteristics will be integrated into the analysis so that relative efficacy can be estimated for different patient groups; and 3) Develop decision support tools, using the information from the NMAs, to help individualize treatment based on patients' characteristics and preferences. This research is designed to contribute to a better understanding of the comparative effectiveness and safety of antiretroviral agents will improve ART guidelines, clinical decision-making, and ultimately patient outcomes.