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Despite global advances in the treatment and prevention of HIV, adolescent girls and young women (AGYW, aged 15-24) remain vulnerable to HIV acquisition in sub-Saharan Africa (SSA). There, AGYW outnumber their male peers in terms of HIV incidence three to one, and account for nearly two-thirds of all incident HIV infections. Pre-exposure prophylaxis (PrEP), which is 99% effective at preventing HIV, could contribute to reducing the burden of HIV among AGYW if used at scale and effectively. Nevertheless, awareness of PrEP in high HIV burden settings—especially among populations most vulnerable to HIV acquisition such as AGYW—remains unacceptably low and presents a primary barrier for effective PrEP coverage. Compounding this low awareness of PrEP are three interrelated drivers of behaviors that put AGYW at risk of adverse sexual and reproductive health (SRH) outcomes: 1) inequitable gender views, 2) poor sexual and reproductive empowerment, and 3) low reproductive autonomy. These three drivers collectively form a set of documented upstream determinants to poor sexual health outcomes, including reduced engagement in preventive health care, such as condom, contraceptive, and/or PrEP use. This dissertation is thus motivated by the overarching question: “How might AGYW-centered interventions improve the realization of SRH intentions and subsequent SRH outcomes among AGYW in east and southern Africa?”. To address this question, I use data from studies conducted in three countries and designed in collaboration with AGYW and with the purpose of understanding how to reduce inequitable gender views, improve sexual and reproductive empowerment, and increase reproductive autonomy as intermediaries to larger, downstream health behaviors (Chapters 1 and 3). For Chapter 2, I conduct primary data collection for a discrete choice experiment to understand AGYW’s preferences for potential HIV prevention implementation models, specifically for PrEP.In Chapter 1, I leverage data from a Type 2 Effectiveness-Implementation cluster randomized controlled trial (CRCT) of CyberRwanda, a digital SRH intervention for Rwandan youth, to examine the intervention’s impact on: 1) inequitable equitable views, and 2) reproductive autonomy. Both inequitable gender views and reproductive autonomy are upstream determinants of a host of SRH outcomes, including contraceptive uptake, experiencing intimate partner violence, and unintended pregnancy, highlighting the potential impact that improving these domains may have on long-term AGYW health and wellbeing. To evaluate the intervention’s impact on these two outcomes, sixty secondary schools in eight districts in Rwanda were randomized 1:1:1 across three arms: two CyberRwanda implementation models (self-service, with unstructured tablet access to the digital platform; or facilitated, which included both unstructured and structured tablet access plus CyberRwanda clubs led by peer facilitators), and a comparison arm. Leveraging data from 2,955 AGYW at 12-months post intervention start and compared to AGYW at comparison schools, AGYW from schools assigned to the CyberRwanda facilitated model experienced small improvements in inequitable gender views and reproductive autonomy; no effect was observed among AGYW at self-service schools. These findings suggest that facilitated digital health interventions among school-age AGYW may be a promising strategy for improving inequitable gender views and reproductive autonomy.In Chapter 2, I report the results of a forced choice discrete choice experiment (DCE) that I designed and conducted with local partners to evaluate preferences for different PrEP modalities and delivery models for AGYW at risk for HIV in Lake Zone, Tanzania. There exist numerous barriers to uptake and retention in PrEP, compounded by low awareness, resulting in preventable HIV cases. With newer PrEP modalities (i.e. injectable, vaginal ring) under regulatory review, we are at an opportune juncture where an understanding of AGYW preferences could ensure that implementation of future PrEP modalities could be grounded in users’ preferences. We enrolled 696 AGYW who met the criteria of being recently (n=138) or currently (n=558) PrEP eligible, and evaluated five attributes: (i) PrEP modality, (ii) screening location, (iii) refill location, (iv) provider identity, and (v) cost per refill. Results show that prior to the educational module explaining PrEP (which preceded the DCE), knowledge of PrEP was low—less than 1 in 5 respondents had ever heard of PrEP. Modality of PrEP, specifically injectable PrEP, was the most preferred and influential component driving AGYW preferences. Respondents reported high levels of interest in taking up PrEP across various implementation scenarios, demonstrating that newer modalities of PrEP, such as long-acting injectables, may help close the gap between unmet need for PrEP and barriers to uptake of current PrEP modalities.In Chapter 3, I leverage data from the ‘SKILLZ’ study, a Type 1 hybrid effectiveness-implementation CRCT evaluating the impact of SKILLZ, a peer-led, sports-based program intended to empower adolescent girls implemented by Grassroot Soccer (GRS) in Zambia. Sports-based programming is associated with delayed sexual debut and higher empowerment among AGYW, yet these relationships have not been rigorously evaluated via a CRCT. The study enrolled 2,153 AGYW across 46 secondary schools in and surrounding Lusaka, Zambia; my dissertation evaluates the impact of the intervention on sexual and reproductive empowerment, measured via the Sexual and Reproductive Empowerment (SRE) for Adolescents and Young People scale. Results show small to moderate impacts of the intervention on SRE, with these impacts magnified for those who were sexually active and those who attended more than eight of twelve sessions. The central hypothesis linking the three chapters is that interventions developed by and for youth that reduce barriers to engaging in sexual health care will result in reduced inequitable gender views and improved sexual and reproductive empowerment and reproductive autonomy, all of which are key determinants of subsequent uptake and engagement with SRH and HIV prevention. The development of each of the interventions evaluated herein is consistent with several internationally recognized frameworks guiding AGYW-focused SRH research and intervention design, such as those developed by the Human-centered Design (HCD) Exchange and the World Health Organization. Further, the focus on upstream determinants of SRH health, such as gender views and reproductive autonomy and empowerment, aligns with World Health Organization priorities to ensure universal access to SRH to improve quality of life and reduce health inequalities. Taken together, the knowledge generated from this research may lead to a better understanding of how to address upstream determinants of poor HIV and SRH care among AGYW, as well as provide timely information to influence policy on the roll-out of novel PrEP products. Further, they may provide insight on effective programs and policies related to HIV and SRH care among AGYW among other southern- and eastern- African countries.