# Optimizing PrEP regimens for pregnant women in sub-Saharan Africa

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $300,000

## Abstract

PROJECT SUMMARY
Women in sub-Saharan Africa face an unacceptably high risk of HIV acquisition during pregnancy and
breastfeeding. Daily oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate
(FTC/TDF) is effective in reducing HIV acquisition and is recommended in pregnancy. At standard FTC/TDF
doses, however, tenofovir drug concentrations are 23-58% lower during pregnancy, raising concerns about
reduced efficacy. In this study, we seek to identify and evaluate the optimal dose of FTC/TDF for daily oral PrEP
in pregnancy, focusing on pharmacokinetic (PK) and safety outcomes. To accomplish our aims, we plan several
key activities. Dose identification (Stage 1): We will randomize 45 pregnant women at 14-24 weeks gestation
to three different FTC/TDF doses—standard dose (200mg/300mg), 150% standard dose (300mg/450mg), and
200% standard dose (400mg/600mg). Each participant will undergo three “cycles” comprising 14 days of daily
oral PrEP, followed by intensive PK sampling over 24 hours. The first two cycles will occur in the second and
third trimesters of pregnancy at the assigned FTC/TDF dose; the third will take place at 12 weeks postpartum
and use only standard FTC/TDF. We will compare tenofovir diphosphate in peripheral blood mononuclear cells
(PBMCs) in each pregnancy trimester to the postpartum control condition, using defined boundaries for
bioequivalence. Preliminary safety data will also be obtained. Independent review: Findings from this initial
stage will be independently reviewed by an expert, multidisciplinary Study Monitoring Committee, which will
recommend an increased FTC/TDF dose (150% vs. 200% standard dose) for further study. Extended safety
assessment (Stage 2): We will randomize 112 pregnant women at 14-24 weeks gestation to receive either
standard vs. increased FTC/TDF doses on a daily basis, under direct observation, until time of delivery. Safety
monitoring will continue through pregnancy, delivery, and the first six months postpartum. We will compare renal
function, adverse events, bone mineral density, weight change/growth in women and infants, and pregnancy
outcomes. We will evaluate FTC and TFV (and their metabolites) in plasma, PBMCs, red blood cells, urine, and
cervicovaginal fluid. PK modeling: Using empiric study data, we will develop a PK model that estimates
concentrations of FTC and TDF across multiple compartments during pregnancy. Our model will consider key
factors that may influence drug concentrations (e.g., body weight, gestational age, renal function) to predict
safety outcomes for lengthier exposures in pregnancy. This study will be led by an experienced team of
researchers, with extensive expertise in HIV, clinical trials, pharmacology, and obstetrics. Our proposal leverages
the strengths of its partnering institutions, including the robust research infrastructure at the University of
Zimbabwe. Over the course of this award, we will provide key insights into the PK and safety of...

## Key facts

- **NIH application ID:** 10810828
- **Project number:** 5R01AI157859-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** PETER L. ANDERSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $300,000
- **Award type:** 5
- **Project period:** 2021-04-13 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810828

## Citation

> US National Institutes of Health, RePORTER application 10810828, Optimizing PrEP regimens for pregnant women in sub-Saharan Africa (5R01AI157859-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10810828. Licensed CC0.

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