PROJECT SUMMARY Women in sub-Saharan Africa face an unacceptably high risk of HIV acquisition during pregnancy and breastfeeding. While services to prevent mother-to-child HIV transmission have expanded rapidly in the region, few prevention interventions exist for the majority of pregnant women who initially test HIV-negative. This is a major missed opportunity that has implications not only for the index woman, but for her partner and infant as well. To address this public health gap, we propose a comprehensive dyadic approach to HIV prevention that extends from antenatal services. Partner dyads are considered after antenatal HIV testing, which is near universal in many settings. They are then categorized into one of six groups based on HIV serostatus of the pregnant woman (positive or negative) and her male partner (positive, negative, or unknown). To optimally reduce horizontal and vertical HIV transmission, a comprehensive HIV prevention package must address each at-risk population through behavioral and biomedical interventions. We propose a three-phased study. First, we will collect and synthesize background information through systematic reviews, mathematical modeling, and formative research. These exercises will deliver a comprehensive overview of the field, while providing insight into the social and cultural nuances of HIV prevention in this vulnerable population. Second, we will consolidate these findings to develop an HIV prevention package for pregnant women, their partners, and their infants. This will be accomplished though technical consensus meetings and dissemination-revision cycles with stakeholders representing the community, health systems, and policymakers. Third, we will evaluate components of this package for feasibility and programmatic effectiveness at the University of North Carolina's flagship sites in Zambia and Malawi. We propose studies that are designed to: (1) assess the implementation of a combination, choice-driven strategy to increase male partner HIV testing, (2) evaluate the effectiveness of a dyad-focused navigation intervention for HIV-infected partners in a randomized trial, and (3) determine the feasibility of pre-exposure prophylaxis (PrEP) among HIV-uninfected pregnant women at risk for HIV infection. To carry out these aims, we have recruited an experienced, multidisciplinary faculty of obstetricians, HIV specialists, implementation researchers, behavioral scientists, clinical trialists, epidemiologists, mathematical modelers, biostatisticians, bioethicists, and public health specialists. We have also engaged promising junior African investigators to serve in leadership and co-investigator roles and will mentor them through this highly collaborative initiative. At the end of the four-year award, we will have developed – through rigorous formative research and evaluation – a combination HIV prevention package for pregnant women, their partners, and their newborns. We will have also gathered the feasibil...