Evaluation of pharmacokinetics of Tenofovir Alafenamide (TAF) and Tenofovir Disoproxil (TDF) in pregnant and postpartum women in South Africa: PrEP-PP PK study.

BACKGROUND: There are few data on tenofovir-diphosphate (TFV-DP) concentrations in pregnant and postpartum women on Tenofovir Disoproxil Fumarate-Emtricitabine (TDF-FTC) or Tenofovir Alafenamide-Emtricitabine (TAF-FTC). METHODS: Eligible pregnant women were randomized to TDF-FTC or TAF-FTC and followed for 16 weeks (8-weeks pregnant, 8-weeks postpartum) with weekly collection of dried blood spot (DBS) and 4-weekly peripheral blood mononuclear cells (PBMC). PrEP dosing was observed daily via asynchronous videos sent via cell phone. We report geometric means (GM) and their ratios (GMR) with 95% confidence intervals (CIs) for TFV-DP in PBMC and DBS from pregnancy and postpartum. RESULTS: We enrolled N = 39 participants (n = 19 TDF-FTC, n = 20 TAF-FTC): median age was 28 years (IQR:25-34); median gestational age was 24-weeks (IQR:21-28). For TDF-FTC, TFV-DP DBS concentrations at 8-weeks did not differ significantly between pregnancy (GM: 675; 95%CI:537-849) and postpartum (GM: 583; 95%CI:471-722; GMR-TDF = 1.16; 95%CI:0.74-1.80). For TAF-FTC, TFV-DP DBS concentrations at 8-weeks were 44% higher in postpartum (GM: 1199; 95%CI:929-1549) versus pregnancy (GM: 832; 95%CI:751-922; GMR-TAF = 1.44; 95% CI: 1.01-2.06). In PBMC analysis of TDF-FTC, 8-week median TFV-DP (pmol/10^6 cell) was 71 (IQR 44-112) in pregnancy and 73 (IQR 50-102) in postpartum (GMR = 1.04; 95%CI:0.44-2.44). In TAF-FTC, median PBMC at 8-weeks was 580 (IQR:341-985) in pregnancy and 666 (IQR:396-1123) in postpartum (GMR = 1.15; 95%CI:0.30-2.49). CONCLUSION: TFV-DP concentrations were overall lower during pregnancy than postpartum for TAF-FTC. We found high concentrations of TFV-DP in PBMC in pregnancy and postpartum on TAF-FTC, suggesting PrEP efficacy is maintained. Efficacy and safety studies are warranted to evaluate TAF-FTC for PrEP in pregnant and postpartum women.

Initiation and continued use of oral pre-exposure prophylaxis among pregnant and postpartum women in South Africa (PrEP-PP): a demonstration cohort study.

BACKGROUND: When used effectively, oral pre-exposure prophylaxis (PrEP; tenofovir disoproxil fumarate and emtricitabine) prevents maternal HIV acquisition and reduces the risk of vertical transmission. Our study aimed to better understand PrEP initiation, continued use, and adherence in pregnant and postpartum women. METHODS: The PrEP in Pregnancy and Postpartum (PrEP-PP) study is a demonstration cohort study that enrolled pregnant women aged 16 years and older without HIV attending their first antenatal care visit in Cape Town, South Africa, between Aug 29, 2019, and Oct 10, 2021. Eligible, consenting women were followed up quarterly up to 12 months postpartum with regular HIV testing and offer of PrEP with ongoing adherence counselling. The primary outcome was distribution of women across the PrEP cascade (ie, initiation and continuation up to 12 months postpartum) with crude and adjusted hazard ratios (HRs). We also report on HIV incidence by pregnancy and postpartum status. FINDINGS: Overall, 1195 pregnant women were recruited and followed up (median age 26 years, IQR 23-31; median gestational age 21 weeks, IQR 15-31); 1009 (84·4%) started PrEP at enrolment. Among women who initiated PrEP at enrolment, 668 (67·5%) of 990 continued PrEP at the 1-month follow-up, 485 (49·9%) of 972 continued at 3 months, 392 (39·4%) of 994 at 6 months, and 275 (27·4%) of 1005 at 12 months. Of 186 women who did not accept PrEP at enrolment, 70 (37·6%) of 186 subsequently initiated PrEP. Overall, 200 (18·6%) of 1076 women continued PrEP at 12 months postpartum. Of 186 women who did not initiate PrEP at baseline, 70 (37·6%) subsequently initiated PrEP during the study. Factors associated with PrEP discontinuation up to 12 months postpartum included being married or cohabiting (adjusted HR 1·32, 95% CI 1·16-1·50), condomless sex since last visit (1·43, 1·23-1·65), reporting intimate partner violence (2·03, 1·59-2·59), or depression in the past 12 months (1·53, 1·14-2·05). Overall, 16 women seroconverted over 1673·8 woman-years (HIV incidence rate 0·96 per 100 woman-years, 95% CI 0·49-1·42); 14 discontinued PrEP use and two never initiated PrEP. HIV incidence was 0·28 per 100 woman-years during pregnancy (95% CI 0·22-0·33), and the incidence rate ratio was 1·77 per 100 woman-years (0·53-5·90) 0-6 months postpartum and 2·19 per 100 woman-years (0·61-7·83) 6-12 months postpartum compared with pregnant women. INTERPRETATION: There is an urgent need for the integration of PrEP into antenatal and postnatal care and interventions that address barriers to continued use, including targeted counselling during pregnancy and postpartum to reduce PrEP discontinuation. FUNDING: National Institute of Mental Health and Fogarty International, US National Institutes of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Pregnancy outcomes following self-reported and objective-measured exposure to oral preexposure prophylaxis in South Africa.

OBJECTIVE: To compare pregnancy outcomes using self-reported and objective levels of intracellular tenofovir diphosphate (TFV-DP) in pregnant women using preexposure prophylaxis (PrEP). DESIGN: We enrolled pregnant women >15 years without HIV at first antenatal care visit in an observational cohort study to compare pregnancy outcomes by PrEP use. METHODS: Exposure defined as: any PrEP use [tenofovir disoproxil and emtricitabine (TDF/FTC]) prescription + reported taking PrEP], or objectively-measured TFV-DP in dried blood spots in PrEP-using pregnant women. The primary outcome was a composite of pregnancy loss, preterm birth (<37weeks), low birthweight (<2500 g), small for gestational age ([SGA] ≤ tenth percentile), or neonatal death. Multivariable logistic regression models evaluated individual and composite adverse outcomes by self-reported or objectively measured PrEP use adjusting for age, gestational age, gravidity and socio-economic status. RESULTS: Between August 19 and February 23, we followed 1195 pregnant women and ascertained 1145 pregnancy outcomes (96%); 72% ( n  = 826) reported taking PrEP while pregnant, 16% did not take PrEP ( n  = 178), 12% were unconfirmed ( n  = 141). Overall, 94.5% ( n  = 1082) had singleton live births with a median birthweight of 3.2 kg [interquartile range (IQR) = 2.9-3.5], with no difference in pregnancy loss between self-reported PrEP exposed vs. unexposed [4.0 vs. 5.6%; adjusted odds ratio (aOR) = 0.65, 95% confidence interval (CI) = 0.32-1.47]. Composite adverse outcomes did not differ by reported PrEP use (20% for both groups; aOR = 1.07, 95% CI = 0.71-1.63). Comparing objective PrEP use (any TFV-DP vs. no TFV-DP or not on PrEP), adverse outcomes did not differ (aOR = 0.64, 95% CI = 0.39-1.04), nor did other outcomes including preterm birth nor SGA. CONCLUSIONS: Pregnancy outcomes did not differ by PrEP exposure (self-reported or objective), suggesting real-world efficacy that TDF/FTC as PrEP is safe in pregnancy.

Integration of HIV pre-exposure prophylaxis (PrEP) services for pregnant and breastfeeding women in eight primary care clinics: results of an implementation science study.

Background: Although HIV vertical transmission (VT) has declined significantly in sub-Saharan Africa, incident HIV infection in pregnant and postpartum women is estimated to account for roughly one-third of VT. Oral pre-exposure prophylaxis (PrEP) for pregnant and breastfeeding women (PBFW) is part of the recommended guidelines in South Africa since 2021; however, integration of PrEP services within antenatal (ANC) and postnatal care (PNC) remains limited. Methods: Between March 2022 and September 2023, we evaluated the acceptability, feasibility and sustainability of integrating PrEP for PBFW in high-HIV prevalence clinics after training and mentoring health care providers (HCP). We used the Reach Effectiveness-Adoption Implementation Maintenance (RE-AIM) framework to evaluate the intervention. Acceptability and maintenance were defined as the proportion of PBFW without HIV who initiated PrEP and the proportion of women continuing PrEP at 3 months in ANC or PNC services. Feasibility was defined as the proportion of trained HCPs (HIV lay counsellors and nurses/ midwives) who provided PrEP according to national guidelines, measured through post-training surveys and in-service assessments. Sustainability was defined as number of facilities and providers that continued to provide PrEP for PBFW past the mentoring period. Results: In 8 facilities providing ANC and PNC, we trained 224 HCP (127 nurses and 37 counsellors). Of those, we mentored 60 nurses, midwives and HIV counsellors working with PBFW, with 72% of nurse/midwives and 65% of counsellors scoring over 8/10 on the final mentoring assessment Overall, 12% (1493/12,614) of HIV-negative pregnant women started PrEP and 41% of those continued PrEP at 3-months. Among the HIV-negative breastfeeding women in postnatal care, 179/1315 (14%) initiated PrEP and 25% continued PrEP at 3-months. All 8 facilities continued providing PrEP 3-months after handover of the clinics. Conclusion: Integration of PrEP services in ANC and services for breastfeeding women was feasible, acceptable and sustainable. Acceptability and PrEP continuation showed improvement over time. Barriers to the PrEP integration were observed including the lack of regular HIV testing of breastfeeding mothers and need for ART-trained nurses to prescribe PrEP. Enablers included motivated and dedicated staff.