High PrEP uptake and objective longitudinal adherence among HIV-exposed women with personal or partner plans for pregnancy in rural Uganda

BackgroundIn Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. Oral pre-exposure prophylaxis (PrEP) reduces HIV acquisition risk for women and, therefore, infants. We conducted a longitudinal cohort study in Uganda to evaluate oral PrEP uptake and adherence as part of HIV prevention in the context of reproductive goals for women (i.e., safer conception care). MethodsWe enrolled HIV-negative women with personal or partner plans for pregnancy with a partner living, or thought to be living, with HIV (2017-2020) to evaluate the impact of the Healthy Families intervention on PrEP use. Quarterly study visits through 9 months included HIV and pregnancy testing, and safer conception counseling. PrEP was provided to women in electronic pillboxes as the primary adherence measure (categorized as "high" with pillbox openings on >80% of days). Enrollment questionnaires assessed factors associated with PrEP use. Plasma tenofovir (TFV) and intraerythrocytic TFV-diphosphate (TFV-DP) concentrations were determined at each visit for women who acquired HIV during follow-up and a randomly selected subset of those who did not. Women who became pregnant were initially exited from the cohort by design; from April 2019, women with incident pregnancy remained in the study with quarterly follow-up until pregnancy outcome. Primary outcomes included (1) PrEP uptake (proportion of enrolled women who initiated PrEP) and (2) PrEP adherence (proportion of days with electronic pillbox openings during the first 3 months following PrEP initiation). We used univariable and multivariable-adjusted linear regression to evaluate baseline predictors of mean adherence over 3 months. We also assessed mean monthly adherence over 9 months of follow-up and during pregnancy. ResultsWe enrolled 131 women with a mean age of 28.7 years (95% CI: 27.8-29.5). Ninety-seven (74%) reported a partner with HIV and 79 (60%) reported condomless sex at last encounter. Most women (N=118; 90%) initiated PrEP. Mean electronic adherence during the 3 months following initiation was 87% (95% CI: 83%, 90%); most (85%) had adherence >80%. No covariates were associated with 3-month pill-taking behavior. Plasma TFV concentrations were >40ng/mL among 66%, 56%, and 45% at months 3, 6, and 9, respectively. TFV-DP concentrations were >600 fmol/punch among 47%, 41%, and 45% of women at months 3, 6, and 9. We observed 53 pregnancies among 131 women with 848 person-months of follow-up (annualized incidence 75% [95% CI: 57%, 98%]) and one HIV-seroconversion in a non-pregnant woman accessing PrEP. Mean pillcap adherence for PrEP users with pregnancy follow-up (N=17) was 98% (95% CI: 97%, 99%). ConclusionsWomen in Uganda with PrEP indications and planning for pregnancy chose to use PrEP. By electronic pillcap, most were able to sustain high adherence to daily oral PrEP prior to and during pregnancy. Differences in adherence measures highlight challenges with adherence assessment and serial measures suggest 41-66% of women took sufficient periconception PrEP to prevent HIV. These data suggest that women planning for and with pregnancy should be prioritized for PrEP implementation, particularly in settings with high fertility rates and generalized HIV epidemics.