Evaluating PrEP use and safety among women of reproductive age in sub-Saharan Africa

Randy Stalter | 2021

Advisor: Jared Baeten

Research Area(s): Global Health, Infectious Diseases

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In sub-Saharan Africa, oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) has emerged as an important HIV prevention strategy for women and is being scaled up rapidly in areas with high HIV burden. New, long-acting PrEP methods are also approaching introduction, including the dapivirine vaginal ring, which women can wear continuously and discreetly for up to one month. Greater choice means women are more likely to find a method that suits their specific needs and preferences. However, questions and challenges regarding PrEP use and safety among women of reproductive age remain, which we aimed to address in this dissertation.

First, we validated a novel, urine-based tenofovir immunoassay as a potential point-ofcare tool for assessing PrEP adherence using stored samples from the Partners PrEP Study (Chapter 2). Second, we estimated the per-sex-act relative HIV risk reduction among women exhibiting consistent use of the dapivirine ring in the ASPIRE trial based on an objective measure of ring exposure, the rate of dapivirine release from returned rings (Chapter 3). Third, we evaluated differences in changes in bone turnover markers associated with combined use of oral PrEP and depot medroxyprogesterone acetate (DMPA) among young women in Uganda (Chapter 4). Finally, we conducted a literature review on the safety of TDF-based PrEP use during pregnancy (Chapter 5). We demonstrated that urine tenofovir concentrations measured by the novel immunoassay has good sensitivity (87%) and specificity (73%) for detecting tenofovir in plasma.

Additionally, tenofovir concentrations over a certain threshold indicative of PrEP use in the past day were predictive of a 71% reduction in HIV risk. We established the first per-sex-act doseresponse model for dapivirine ring exposure and estimated 61% per-sex-act risk reduction with ring release rates indicative of continuous ring use. We identified no substantial changes in bone turnover biomarkers after 6 months of combined DMPA and PrEP use. Finally, we found that the current body of evidence on the safety of TDF-based PrEP use during pregnancy is reassuring but that additional data are needed. Additionally, more efforts are needed to increase representation of pregnant women in studies of new HIV prevention products.

The findings from this dissertation contribute to efforts for improving women’s uptake of and adherence to PrEP in the coming years by validating a novel urine-based tenofovir immunoassay and providing a better understanding the efficacy of the dapivirine ring. Additionally, this work provides reassuring data on the safety of PrEP use during periods of contraception and pregnancy which may help to facilitate integration of PrEP into family planning and antenatal care services.