# PrEP adherence-concentration thresholds associated with HIV protection among African women

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $731,299

## Abstract

ABSTRACT
African women are disproportionately affected with HIV and have elevated risk of acquiring HIV in pregnancy.
Pre-exposure prophylaxis (PrEP) is a potent HIV prevention strategy, but variable adherence in PrEP clinical
trials among women and limited pharmacologic data have resulted in lack of clarity about the degree of PrEP
use required for HIV protection in cisgender women. For US men who sex with men, the DOT-DBS and STRAND
studies of PrEP delivered as directly-observed therapy (DOT) defined precisely the target tenofovir diphosphate
(TFV-DP) concentrations arising from varying number of PrEP doses per week (i.e., 2, 4, 7 doses/ week); when
these data were then applied to the iPrEx trial cohort, they defined robust adherence-efficacy thresholds for men.
Single-dose tissue pharmacology studies have suggested that women have lower genital tissue compared with
male rectal concentrations, potentially implying women need extraordinarily high PrEP adherence to achieve
similar HIV protection; however, clinical studies in women with reasonable-but-imperfect PrEP adherence
suggest high levels of HIV protection. At root of this controversy is the lack of data that link cumulative PrEP
dosing thresholds with PrEP efficacy in women. Recently, data our team and the IMPAACT 009 Study have
generated from PrEP studies in African women suggest the STRAND levels may not truly reflect the
pharmacology of PrEP in African settings, both in general and particularly in pregnancy: These data suggest
differences in TFV-DP levels may be as great as 30-40% between pregnant and postpartum women. However,
the IMPAACT 009 study did not measure TFV-DP concentrations in PBMCs which are required to ascertain
whether the observed levels may compromise HIV protection in pregnancy. To state it explicitly, the adherence-
efficacy thresholds developed by DOT dosing in US populations may not be accurate for women in Africa and
thus interpreting women's PrEP adherence-concentration-efficacy relationships in that lens will be erroneous.
Indeed, the absence of clinical data linking intracellular concentrations to HIV protection for tenofovir disoproxil
fumarate (TDF) PrEP prevented the FDA from extending the tenofovir alafenamide (TAF) / emtricitabine (FTC)
PrEP indication to women. We have assembled a strong team with truly multidisciplinary synergy, including
leaders in the PrEP field, to conduct a novel randomized pharmacologic study to define women-specific
adherence-concentrations thresholds derived from varying frequency of DOT TDF/FTC PrEP (Aim 1). We will
take a comprehensive approach: DOT dosing, sampling from week one to steady-state, including a pregnancy
cohort, and pharmacologic measurement in multiple biologic matrices (plasma, whole blood, dried blood spots,
PBMC, and vaginal tissue). Then, leveraging archived samples, in a case-cohort study of those who acquired
HIV and a subset remaining HIV-uninfected from the Partners PrEP Study, we will define TFV-DP concen...

## Key facts

- **NIH application ID:** 10773059
- **Project number:** 5R01AI155086-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** PETER L. ANDERSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $731,299
- **Award type:** 5
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10773059

## Citation

> US National Institutes of Health, RePORTER application 10773059, PrEP adherence-concentration thresholds associated with HIV protection among African women (5R01AI155086-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10773059. Licensed CC0.

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