ABSTRACT Over 16 million children are HIV-exposed and uninfected (HEU) globally, many of whom were also exposed to maternal antiretroviral drugs in utero and/or during breastfeeding. Over a quarter of all adolescents ≥10 years of age in Botswana are HEU. Children and adolescents who are HEU experience increased risk of infectious morbidity, mortality, poorer growth and neurodevelopmental delays compared to those born HIV-unexposed uninfected (HUU). Yet, much of the research to date following outcomes in this population has focused on assessing health and neurodevelopmental disparities occurring in infancy, childhood, or adolescences. Little is known about associations between gestational exposure to HIV and antiretroviral (ARV) drugs, growing up in a household affected by HIV and adult health outcomes, including cardiometabolic health, reproductive health, cancer risk, or mental health. We have the potential to follow adolescents who are HEU into young adulthood, with detailed prospectively collected data on their in utero exposures, including maternal viral load and specific ARV drugs in the Botswana- based FLOURISH study (R33 HD103099) . However, only 41% of caregivers participating in the FLOURISH study had disclosed their HIV status to their adolescents who are HEU. Contextually appropriate tools and approaches are urgently needed to support caregiver disclosure of HIV exposure status to their adolescents, creating the opportunity for longitudinal surveillance of health and wellbeing outcomes into adulthood. Employing a multi-methods study design. the Disclosure Intervention to Support Caregivers (DISC) study will advance an understanding of the benefits of disclosure while facilitating the development of a contextually appropriate disclosure tool designed to prepare caregivers for a disclosure discussion and provide caregivers with skills for assessing their adolescent’s wellbeing post disclosure through the three scientific aims, including 1) evaluating whether caregiver disclosure of HIV status is associated with lower prevalence of depression and anxiety for both caregivers and adolescents, as well as improved parent-adolescent relationships, where disclosure has occurred compared to dyads where disclosure has not occurred; 2) developing tools to support caregiver disclosure of HIV status to adolescents who are HEU, relying on in-depth interviews, focus group discussions, and human- centered participatory design workshops with FLOURISH caregivers and adolescents; and 3) assessing acceptability, feasibility, and appropriateness of the newly designed disclosure support tool among a subset of FLOURISH caregivers who have not yet disclosed to their adolescents.