BackgroundYouth orphaned by HIV in sub–Saharan Africa experience immense hardships including social disadvantage, adverse childhood events and limited economic prospects. These adversities disrupt the normative developmental milestones and can gravely compromise their health and emotional wellbeing. TheBridges to the Futurestudy (2012–2018) prospectively followed 1,383 adolescents, between 10–16 years, to evaluate the efficacy and cost-effectiveness of a family-based economic empowerment intervention comprising of child development accounts, financial literacy training, family income generating activities and peer mentorship. Study findings show efficacy of this contextually-driven intervention significantly improving mental health, school retention and performance and sexual health. However, critical questions, such as those related to the longitudinal impact of economic empowerment on HIV prevention and engagement in care remain. This paper presents a protocol for the follow-up phase titled,Bridges Round 2.MethodsTheOriginal Bridgesstudy participants will be tracked for an additional four years (2022–2026) to examine the longitudinal developmental and behavioral health outcomes and potential mechanisms of the effect of protective health behaviors of theBridgescohort. The study will include a new qualitative component to examine participants’ experiences with the intervention, the use of biomedical data to provide the most precise results of the highly relevant, but currently unknown sexual health outcomes among study participants, as well as a cost-benefit analysis to inform policy and scale-up.DiscussionStudy findings may contribute to the scientific knowledge for low-resource communities on the potential value of providing modest economic resources to vulnerable boys and girls during childhood and early adolescence and how these resources may offer long-term protection against known HIV risks, poor mental health functioning and improve treatment among the HIV treatment care continuum.