Tenofovir Diphosphate Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan Africa

Abstract

Background Intracellular tenofovir diphosphate (TFV-DP) concentration measured in dried blood spots (DBS) is used to monitor cumulative adherence to pre-exposure prophylaxis (PrEP). We evaluated TFV-DP in DBS following daily oral PrEP (emtricitabine 200mg/tenofovir diphosphate 300mg) among pregnant and postpartum adolescent girls and young women (AGYW). Methods Directly observed PrEP was administered for 12 weeks in a pregnancy group (14-24 weeks gestation, n=20) and a postpartum group (6-12 weeks postpartum, n=20) of AGYW aged 16-24 years in sub-Saharan Africa. Weekly DBS TFV-DP was measured by validated liquid chromatography-tandem mass spectrometry assay. Week 12 TFV-DP distributions were compared between groups with the Wilcoxon test. Population pharmacokinetic models were fit to estimate steady-state concentrations and create benchmarks for adherence categories. Baseline correlates of TFV-DP were evaluated. Results Participant median age was 20 years (IQR:19,22). Of 3360 doses, 3352 (>99%) were directly observed. TFV-DP median half-life was ten days (IQR:7, 12) in pregnancy and 17 days (IQR:14, 21) postpartum, with steady-state achieved by five and eight weeks, respectively. Observed median steady-state TFV-DP was 965 fmol/punch (IQR:691, 1166) in pregnancy vs 1406 fmol/punch (IQR:1053, 1859) postpartum (p=0.006). Modelled median steady-state TFV-DP was 881 fmol/punch (IQR: 667,1105) in pregnancy vs 1438 fmol/punch (IQR: 1178,1919) postpartum. In pooled analysis, baseline creatinine clearance was associated with observed TFV-DP concentrations. Conclusion TFV-DP in African AGYW was approximately one-third lower in pregnancy than postpartum. Population-specific benchmarks provided by this study can be used to guide PrEP adherence support in pregnant/postpartum African women.

Barriers to Oral HIV Pre-exposure Prophylaxis (PrEP) Adherence Among Pregnant and Post-partum Women from Cape Town, South Africa

“…There is limited literature on PrEP among this population, but some data suggest that PrEP adherence may be poor, particularly among postpartum women [ 8 , 9 ]. Daily adherence to oral PrEP is important for achieving adequate levels of protection and studies have found that tenofovir levels are lower during pregnancy and/or postpartum compared to non-pregnant or non-lactating women [ 10 , 11 ]. While newer long-acting PrEP drugs such as injectable cabotegravir might alleviate some challenges with adherence, it is likely to be several years before these products are widely available for use among pregnant and breastfeeding women.…”

Maternal PrEP Use in HIV-Uninfected Pregnant Women in South Africa: Role of Stigma in PrEP Initiation, Retention and Adherence

“…While pregnant women have been excluded from clinical trials of PrEP due to unknown effects of FTC/TDF on pregnancy outcomes, the World health organization (WHO) recommends PrEP use among pregnant and breastfeeding women following recent trials and reviews which suggest that PrEP is safe and effective in preventing HIV among this population [18,19]. Despite these successes, continuation in PrEP care and adherence to PrEP remain challenges, especially among pregnant and postpartum women, among whom emerging pharmacokinetic evidence suggests that blood levels of TDF among African AGYW were about one third lower in pregnancy than in postpartum, indicating the need for daily PrEP adherence to maintain effectiveness against HIV infection [20][21][22].…”

Early pre-exposure prophylaxis (PrEP) discontinuation among pregnant and postpartum women: Implications for maternal PrEP roll out in South Africa

“…This consideration is essential in pregnant women who require daily dosing for efficacy, given that non-adherence is less forgiving than in postpartum women. (32)…”

“…Survey measures were collected at baseline and follow-up visits for all participants (on PrEP and not on PrEP). Survey measures included questions on: (a) basic demographic information and obstetric history (baseline only), (b) partner HIV status, (c) sexual behaviours in the past month and past week (including the number of sex partners, type of sex, frequency of sex and condom use), (d) substance use from the Alcohol Use Disorders Identification Test (AUDIT) (31) and Drug Use Disorders Identification Test (DUDIT) (32), (e) HIV risk perception, (f) intimate partner violence (using the WHO IPV scale (33,34)), (g) perceived partner, community and social support for PrEP, and (h) for PrEP users only, questions related to PrEP adherence according to self-report (seven-day and 30-day recall) and pill count measures, side effects, adverse events, severe adverse events and birth outcomes (after participants have given birth) at follow-up visits.…”