Improving Pre-exposure Prophylaxis (PrEP) delivery for HIV prevention among women of reproductive age in Sub-Saharan Africa

Adolescent girls and young women in East and Southern Africa are disproportionately affected by HIV. Tenofovir disoproxil fumarate (TDF)-based oral pre-exposure prophylaxis (PrEP) reduces the risk of HIV acquisition with consistent daily adherence and has been recommended for use since 2015 by the World Health Organization. However, for a multitude of reasons, young African women have difficulty adhering to daily pill-taking and/or accessing refills for oral PrEP. TDF-based oral PrEP is generally safe but has been linked with low levels of bone mineral density (BMD) loss. Research is needed to evaluate if the use of TDF-based oral PrEP during pregnancy exacerbates maternal bone mineral density loss. Further, drug level monitoring (accompanied by feedback) and data-driven adherence counseling are essential to supporting young women using PrEP. Novel tools such as point-of-care tenofovir (POC TFV) urine test may have a significant impact on improving PrEP adherence. In addition to research to optimize the use of daily oral PrEP, new products with longer-acting formulations have been proven efficacious and are nearing programmatic implementation. These products, including an injection and a vaginal ring, have the potential to overcome the challenges of daily adherence and curtail the high HIV burden among African women. By leveraging data from recent prospective cohort studies, we aimed to contribute to global efforts to optimize PrEP delivery to young women through this dissertation.Our first study leveraged data from women enrolled in a prospective cohort study evaluating the impact of concurrent TDF-based PrEP and DMPA on bone health in Kampala, Uganda. In a sub-study of women who became pregnant in that cohort, we evaluated the impact of TDF-based PrEP use on BMD loss during pregnancy. Secondarily, we investigated the effect of pregnancy on daily oral PrEP adherence and continuation. We observed significant BMD loss among pregnant women who were using PrEP, which was likely driven by pregnancy, rather than PrEP use. Our study also reported that women experiencing pregnancy were significantly less likely to use PrEP than women without a pregnancy through analyses comparing pregnant versus non-pregnant women and pregnant versus non-pregnant periods among women who become pregnant. Our second study evaluates a recently developed and validated point-of-care urine tenofovir (POC TFV) test to determine whether its use improves the accuracy of self-reported adherence to pre-exposure prophylaxis (PrEP) and sexual behavior. We leveraged data from a prospective cohort of young women using TDF-based oral PrEP in Uganda. We observed that the introduction of a POC urine test for TFV substantially improved the accuracy of self-reported PrEP adherence. We also saw a moderate concordance between the POC urine TFV and TFV-DP in DBS, and greater reports of activities that are traditionally challenging to disclose to an HIV prevention counselor – condomless sex and low PrEP adherence – when the POC urine test was used. Further research is needed to evaluate the utility of POC urine TFV testing to monitor PrEP adherence and inform provider decision-making in clinic settings. However, our findings indicate that the POC urine TFV test could play an important role in PrEP adherence counseling, particularly in a low-resource setting, since it is projected to be low-cost once available commercially. Our third study evaluated preferences and willingness to use novel PrEP products (i.e., injectable cabotegravir and dapivirine vaginal ring) among oral PrEP-experienced and inexperienced Kenyan women accessing family planning clinics. We conducted a cross-sectional study among women seeking services at 12 family planning clinics. We found that an overwhelming number of participants preferred injectable PrEP and would like to switch from their current oral PrEP regimen to injectable PrEP if it were available to them. Among participants without prior PrEP experience, 74% preferred injectable PrEP, 19% preferred oral PrEP, and 4% preferred the vaginal ring. Among previous oral PrEP users, 82% preferred injectable PrEP, 16% preferred oral PrEP, and only 2% preferred the dapivirine vaginal ring. Our findings suggest that in this population of reproductive-age women in Kenya, adding injectable PrEP to the HIV prevention toolkit could potentially increase PrEP use and overall coverage of HIV prevention. Together, the results presented in this dissertation provide insights that have the potential to impact the delivery of daily oral PrEP and plans for the delivery of novel PrEP products to young women in Eastern and Southern Africa. The findings of these studies will inform strategies to support PrEP adherence and continuation among women during pregnancy and the postpartum period, provide novel data on the use of POC TFV testing to support adherence counseling, and inform decisions on novel PrEP product provision for young African women. As newer PrEP products are nearing large-scale implementation, there is a need for making pregnant and adolescent girls, as well as young women, a priority population for these prevention methods, and committing to making these methods available, accessible, and affordable.