Assessing the effect of hormonal contraception on HIV acquisition in observational data: challenges and recommended analytic approaches.

INTRODUCTION Determining whether hormonal contraception, particularly the injectable contraceptive depot-medroxyprogesterone acetate (DMPA), increases a woman's risk of HIV acquisition is a priority question for public health. However, assessing the relationship between various hormonal contraceptive methods and HIV acquisition with observational data involves substantial analytic design issues and challenges. Studies to date have used inconsistent approaches and generated a body of evidence that is complex and challenging to interpret. METHODS In January 2013, the United States Agency for International Development and FHI 360 supported a meeting of epidemiologists, statisticians, and content experts to develop recommendations for future observational analyses of hormonal contraception and HIV acquisition. RESULTS Meeting participants generated recommendations regarding careful definition of exposure groups; handling potential confounders, mediators, and effect modifiers; estimating and addressing the magnitude of measurement error; using multiple methods to account for pregnancy; and exploring the potential for differential exposure to HIV-infected partners. Advantages and disadvantages of various statistical approaches to account for time-varying confounding and estimating total and direct effects were also discussed. CONCLUSION Implementing these recommendations in future observational hormonal contraception-HIV acquisition analyses will enhance interpretation of existing studies and strengthen the overall evidence base for this complex and important area.