Formulating the Future Research Agenda for Postexposure Prophylaxis for HIV: Methodological Challenges and Potential Approaches.

BACKGROUND During a World Health Organization-convened Guideline Development Group meeting, recommendations for postexposure prophylaxis (PEP) for human immunodeficiency virus were made and research gaps identified. METHODS We used the PEP clinical management pathway and the Grading of Evidence, Assessment, Development and Evaluation (GRADE) system as a framework to formulate future research questions, describe the most feasible study design, and identify potential biases. RESULTS Three key study design formats were identified to address 12 research questions: (1) survey- and interview-driven research to identify barriers to access to PEP and related clinical care; (2) establishment of a global PEP registry to generate data to inform the choice of an optimal PEP drug regimen, record drug toxicities arising from specific PEP regimens, and track follow-up and linkage to care (including transition from PEP to preexposure prophylaxis); and (3) randomized controlled trials to determine the optimal adherence promotion strategies necessary for successful outcomes following PEP. CONCLUSIONS Positioning key clinical and programmatic research questions within the GRADE framework facilitates the formulation of an evidence-based research agenda and future revisions of guidelines.