Adherence challenges with daily oral pre‐exposure prophylaxis during pregnancy and the postpartum period in South African women: a cohort study

Abstract

Introduction Daily oral pre‐exposure prophylaxis (PrEP) can reduce HIV acquisition. However, prevention effectiveness requires daily adherence prior to and during periods of sexual activity. Little is known about pharmacologic measures of PrEP adherence during pregnancy and postpartum and the factors related to optimal adherence during periods of sexual activity in this population. Methods Between August 2019 and October 2021, we enrolled pregnant women without HIV at their first antenatal care visit followed‐up through 12 months postpartum. Eligible women ≥16 years old received HIV prevention counselling and were offered oral PrEP (TDF‐FTC). We quantified tenofovir‐diphosphate (TFV‐DP) in dried blood spots in women who reported taking PrEP in the past 30 days (at quarterly follow‐up visits). We used regression models with generalized estimating equations to evaluate correlates of TFV‐DP (any vs. none, and ≥2 vs. <2 doses/week), adjusting for maternal age and pregnancy status. Results and discussion In 382 women who started PrEP in pregnancy, returned for follow‐up and reported PrEP use in the past 30 days, the median age was 27 years (interquartile range [IQR] = 23–32), and the median time on PrEP was 168 days (IQR = 84–252 days). Half of the samples had quantifiable TFV‐DP at any time point (52%), declining from 67% of pregnant women 3 months post‐initiation to 31% of postpartum women by 12 months. Overall, 72% had concentrations corresponding to <2 doses/week; 25% ≥2 doses/week; 3% 7 doses/week. Concentrations were lower in postpartum versus pregnancy (age‐adjusted odds ratio [aOR] = 0.44; 95% confidence interval [CI] = 0.35–0.54). The correlation of self‐reported adherence and TFV‐DP ranged from –0.07 in pregnancy to 0.25 in postpartum women. Variables associated with having quantifiable TFV‐DP included partner living with HIV/unknown serostatus (aOR = 1.50; 95% CI = 1.01–2.22), and reported frequency of sexual activity in the past month (aOR sex >5/month vs. no sex or <5 times/month = 2.11; 95% CI = 1.58–2.82) adjusting for age and pregnancy versus postpartum status. TFV‐DP concentrations declined over follow‐up time (aOR for 6 vs. 3 months = 0.49; 95% CI = 0.36–0.67). Conclusions Objectively measured adherence to PrEP was low overall and did not correlate with self‐reported use. There is an urgent need for objective adherence measures to support clinical decision‐making as well as adherence support interventions as part of PrEP services for pregnant and postpartum women at risk of HIV.

PrEP initiation, persistence, and adherence during pregnancy through the postpartum period: a prospective analysis in Kenya

“…Our findings support that knowledge of partners’ HIV status is important for PrEP use and that women with partners known to be living with HIV are highly motivated to use daily oral PrEP, similar to studies among pregnant PrEP users in South Africa [38]. Dispensing HIV self-tests to pregnant women attending antenatal care to give to their male partners is scaling up in East and Southern Africa to increase testing coverage among men [27,39–42].…”

“…To date, few PrEP studies among pregnant and postpartum women have incorporated objective markers of PrEP adherence. A recent study that followed South African women who initiated PrEP in pregnancy until 12 months postpartum found that 72% of all DBS samples had TFV-DP concentrations corresponding with <2 doses/week [45] and frequency of any quantifiable TFV-DP was higher in pregnancy than postpartum [38]. We similarly found high frequency of TFV-DP concentrations corresponding with <2 doses/week (64% overall) and lower adherence levels postpartum than pregnancy.…”

A Patient-Centered, Combination Intervention to Support Adherence to HIV Pre-exposure Prophylaxis During Pregnancy and Breastfeeding: A Randomized Pilot Study in Malawi

“…Only 2% met the threshold consistent with approximately 7 doses/week. 12 Although different assays and adherence algorithms were used, our estimate for 2-5 doses/week (score of 3 or 4) was similar at 33%. However, we observed a higher proportion with drug levels consistent with daily dosing (score of 5; 10%).…”

“…7,8 Although data are still limited, the available studies suggest that pharmacologically confirmed adherence may also be low in this population. 12 This gap may be particularly important for pregnant and breastfeeding women. Pharmacokinetic/pharmacodynamic modeling suggests that longer lead times may be needed to reach protective tenofovir concentrations in the lower female genital tract.…”

A phase I study to assess safety, pharmacokinetics, and pharmacodynamics of a vaginal insert containing tenofovir alafenamide and elvitegravir

“…Currently, oral tenofovir disoproxil fumarate (TDF) 300 mg in combination with emtricitabine (FTC) 200 mg (Truvada®) is approved for prevention of HIV-1 acquisition in men and women in the United States and several other countries worldwide ( Grant et al., 2010 ; Baeten et al., 2012 ; Thigpen et al., 2012 ). The daily dosing requirement and systemic side effects, primarily gastrointestinal (GI), among other barriers including stigma and lack of support from family or partner, have made it difficult, particularly for AGYWs, to adhere to daily oral TDF/FTC for HIV-1 prevention ( Van Damme et al., 2012 ; Magazi et al., 2014 ; van der Straten et al., 2014b ; Corneli et al., 2015 ; Marrazzo et al., 2015 ; Corneli et al., 2016 ; Amico et al., 2017 ; Joseph Davey et al., 2022 ; Tapsoba et al., 2022 ). Oral tenofovir alafenamide (TAF) combined with FTC (Descovy®), which shows fewer side effects, was recently approved by the United States Food and Drug Administration for HIV-1 prevention, but only among individuals whose primary risk of HIV-1 acquisition is not through vaginal exposure ( Mayer et al., 2020 ).…”