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

Abstract

Background In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. Pre-exposure prophylaxis (PrEP) reduces HIV acquisition for women and, therefore, infants. We developed the Healthy Families-PrEP intervention to support PrEP use as part of HIV prevention during periconception and pregnancy periods. We conducted a longitudinal cohort study to evaluate oral PrEP use among women participating in the intervention. Methods and findings We enrolled HIV–negative women with plans for pregnancy with a partner living, or thought to be living, with HIV (2017 to 2020) to evaluate PrEP use among women participating in the Healthy Families-PrEP intervention. Quarterly study visits through 9 months included HIV and pregnancy testing and HIV prevention counseling. PrEP was provided in electronic pillboxes, providing the primary adherence measure (“high” adherence when pillbox was opened ≥80% of days). Enrollment questionnaires assessed factors associated with PrEP use. Plasma tenofovir (TFV) and intraerythrocytic TFV-diphosphate (TFV-DP) concentrations were determined quarterly for women who acquired HIV and a randomly selected subset of those who did not; concentrations TFV ≥40 ng/mL and TFV-DP ≥600 fmol/punch were categorized as “high.” 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 who initiated PrEP); and (2) PrEP adherence (proportion of days with pillbox openings during the first 3 months following PrEP initiation). We used univariable and multivariable-adjusted linear regression to evaluate baseline predictors selected based on our conceptual framework of mean adherence over 3 months. We also assessed mean monthly adherence over 9 months of follow-up and during pregnancy. We enrolled 131 women with mean age 28.7 years (95% CI: 27.8 to 29.5). Ninety-seven (74%) reported a partner with HIV and 79 (60%) reported condomless sex. Most women (N = 118; 90%) initiated PrEP. Mean electronic adherence during the 3 months following initiation was 87% (95% CI: 83%, 90%). No covariates were associated with 3-month pill-taking behavior. Concentrations of plasma TFV and TFV-DP were high among 66% and 47%, 56% and 41%, and 45% and 45% at months 3, 6, and 9, respectively. We observed 53 pregnancies among 131 women (1-year cumulative incidence 53% [95% CI: 43%, 62%]) and 1 HIV-seroconversion in a non-pregnant woman. Mean pillcap adherence for PrEP users with pregnancy follow-up (N = 17) was 98% (95% CI: 97%, 99%). Study design limitations include lack of a control group. Conclusions Women 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; serial measures of TFV-DP in whole blood suggest 41% to 47% 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. Future iterations of this work should compare the outcomes to current standard of care. Trial registration ClinicalTrials.gov Identifier: NCT03832530 https://clinicaltrials.gov/ct2/show/NCT03832530?term=lynn+matthews&cond=hiv&cntry=UG&draw=2&rank=1.

Sexually Transmitted Infection Prevalence, Partner Notification, and Human Immunodeficiency Virus Risk Perception in a Cohort of Women Completing Sexually Transmitted Infection Screening as Part of a Safer Conception Study

“…This may have been due to the HIV prevention and sexual health counseling that all women received as part of the parent study. Similarly, in a study conducted in Uganda that enrolled HIV-exposed women planning pregnancy and used a similar HIV risk perception scale, perceived HIV risk scores using a 6-item scale were high 33 …”

“…Similarly, in a study conducted in Uganda that enrolled HIV-exposed women planning pregnancy and used a similar HIV risk perception scale, perceived HIV risk scores using a 6-item scale were high. 33…”

HIV Preexposure Prophylaxis With Emtricitabine and Tenofovir Disoproxil Fumarate Among Cisgender Women

“…Women may be motivated to use oral F/TDF for reasons that relate directly to the timing of HIV risk or to perceived benefit. For example, high uptake of F/TDF use was recently reported among HIV-exposed women with plans for pregnancy in rural Uganda . Sexual behaviors that expose women to HIV acquisition also change over time, as demonstrated in the HPTN 064 study, in which social factors were found to influence sustained high-risk behavior, and should be integrated into decisions about approach to PrEP use .…”

“…For the 46 participants who had tenofovir plasma data that were used in the group-based trajectory modeling (ie, not including those with concurrent tenofovir diphosphate measurements in DBS), participants with plasma concentrations greater than or equal to 40 ng/mL were assigned to the high adherence group. This threshold was selected based on prior studies suggesting that 40 ng/mL reflects recent adherence and that participants with pill coverage of at least 80% had plasma tenofovir concentration greater than 40 ng/mL . Participants with concentrations less than 40 ng/mL were included in the low adherence group.…”

Implementation determinants and strategies in integration of PrEP into maternal and child health and family planning services: experiences of frontline healthcare workers in Kenya

“…A study in South Africa observed substantially higher uptake of PrEP at 84% within a trial setting with additional staff; however, it was not possible to assess pre-trial enrollment attrition to determine whether the trial enrolled a population of women more likely to accept PrEP ( 32 ). A Ugandan cohort assessing pre-conception PrEP use among predominantly sero-different couples with fertility intention observed high PrEP uptake at 90%, but did not assess uptake during pregnancy ( 33 ). Future studies should consider how staffing ratios impact not only PrEP uptake, but also upstream steps of PrEP screening, counseling, and offer within busy MCH/FP clinics and test strategies to improve service provision reach broadly without adding new HCW.…”