Prevention of mother-to-child transmission of HIV virtually eliminates transmission of HIV from mothers to their infants. However, adherence to prevention methods (i.e., antiretroviral therapy, infant prophylaxis, and exclusive breastfeeding) during pregnancy and the postpartum period is challenging, with evidence from sub-Saharan Africa showing suboptimal adherence and persistent viremia among perinatal women. As a consequence, rates of vertical HIV transmission remain unacceptably high. Perinatal depression is a major driver of women’s poor adherence to HIV prevention. Interventions that involve male partners to provide social and food/economic support could be a promising approach for addressing perinatal depression and prevention, yet few interventions have intervened with couples to improve systems of support, communication, and other dyadic processes. We propose to develop and test a couple-based approach to intervene on the mother’s perinatal depressive symptoms and to strengthen the relationship and support system for partners to work together around depression to improve adherence to prevention methods. The study will take place in antenatal and HIV care settings in Zomba, Malawi. The specific aims are: (1) to develop a couple-based intervention to target perinatal depression based on an evidence-based approach using problem-solving therapy, augmented with content on couple communication and problem-solving skills; and (2) to assess the feasibility and acceptability of the intervention via a pilot randomized controlled trial (RCT). For Aim 1, we will use an established adaptation framework to develop the intervention manual, study procedures, and data collection instruments and conduct 5 focus group discussions with the target population of couples and key stakeholders to obtain feedback on the intervention content and materials. For Aim 2, we will recruit 60 pregnant women living with HIV with a positive screen for depressive symptoms and their male partners from antenatal/HIV clinics. Couples will be randomized to the intervention or a standard of care control (30 couples per arm) and followed for 3 months postpartum. Primary outcomes will focus on feasibility and acceptability metrics (e.g., enrollment rates, satisfaction levels, retention, and participation rates). Exploratory analyses will examine preliminary effects on the mother’s perinatal depression symptoms, adherence to prevention, food insecurity, and mediating variables such as couple communication. We will also examine whether effects on social support and the mother’s depression are attenuated for couples in which both partners have depression at baseline. In a subset of 15 couples, we will conduct exit interviews to contextualize the data, and will analyze the mixed-methods data to refine the intervention for a full RCT. Our short-term goal is the produce a couple-focused intervention that can be added to the global health toolkit for treating depression in perinatal wome...