Effect of Pregnancy on Intracellular Tenofovir Diphosphate Exposure and Thresholds following Oral Emtricitabine-Tenofovir Disoproxil fumarate Pre-Exposure Prophylaxis: A Directly Observed Dosing Study.

Wu L, Anderson PL, MaWhinney S, +12 more, Women Benchmark Study Team.

Journal ArticleAbstract only — full text under license

AI summary — for doctors, generated from the abstract only

Under directly observed daily oral PrEP dosing, pregnancy lowered tenofovir diphosphate in dried blood spots by about 40% but left concentrations in peripheral blood mononuclear cells essentially unchanged.

What was studied

Eighteen pregnant and 18 non-pregnant healthy Kenyan women without HIV took daily emtricitabine/tenofovir disoproxil fumarate under directly observed dosing for eight weeks, with serial dried blood spot and peripheral blood mononuclear cell (PBMC) sampling. Tenofovir diphosphate (TFV-DP) was quantified by validated liquid chromatography-tandem mass spectrometry and steady-state fitted concentrations compared between groups.

Key findings

99.8% of expected doses (1,922 of 1,925) were directly observed, effectively removing adherence as a confounder
Median age 23 years; median gestational age 16 weeks at enrolment
Estimated creatinine clearance was higher in pregnancy: median 176 mL/min versus 131 mL/min
Steady-state dried blood spot TFV-DP: median 919 fmol/punch in pregnancy versus 1,545 fmol/punch when not pregnant (percent change 40.5%, 95% CI 29.5-51.5%)
PBMC TFV-DP concentrations were not meaningfully different between pregnant and non-pregnant women
Specific PBMC concentration values and revised thresholds not fully captured in the abstract

Clinical relevance

In this small directly observed pharmacokinetic study, the findings imply that lower dried blood spot levels in pregnancy reflect altered red-cell and renal physiology rather than reduced drug exposure at the target cell, so pregnancy-specific adherence benchmarks may be needed when interpreting drug-level monitoring.

Who should care

Infectious Disease

Limitations

Only 36 participants at a single site, all HIV-negative with mid-second-trimester pregnancies, and the design measured drug concentrations rather than clinical protection.

Dried blood spot drug levels understate PrEP exposure during pregnancy, so low values should not automatically be read as poor adherence or inadequate protection.

This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.

Abstract

Introduction

Intraerythrocytic tenofovir diphosphate (TFV-DP) concentrations from emtricitabine/tenofovir disoproxil fumarate (F/TDF) pre-exposure prophylaxis (PrEP) measured in dried blood spots (DBS) are ∼30-40% lower during pregnancy, but data on TFV-DP concentrations in peripheral blood mononuclear cells (PBMCs) are limited. We evaluated the effect of pregnancy on intracellular TFV-DP concentrations in PBMCs.

Methods

Directly observed dosing (DOD) of daily oral F/TDF was administered to 18 healthy non-pregnant and 18 pregnant Kenyan women without HIV for eight weeks. Blood for DBS and PBMC was collected weekly for non-pregnant and bi-weekly for pregnant women. TFV-DP concentrations in DBS and PBMCs were quantified using validated liquid chromatography-tandem mass spectrometry. Steady-state fitted TFV-DP concentrations in PBMC and DBS were compared between pregnant and non-pregnant women.

Results

Median (IQR) age was 23 (20-27) years and gestational age was 16 (14-20) weeks for pregnant women at enrollment. Median (IQR) Cockroft Gault-estimated creatinine clearance was 131 (113-146) mL/Min for non-pregnant versus 176 (154-196) mL/Min for pregnant women. 1922 of 1925 (99.8%) expected doses were directly observed. Fitted steady-state median (IQR) TFV-DP concentrations in DBS were 1545 (1203, 1887) fmol/punch in non-pregnant versus 919 (835, 1003) fmol/punch in pregnant women [percent change: 40.5%, 95%CI (29.5%, 51.5%); p<0.001]. Modeled steady-state geometric mean (95%CI) PBMC TFV-DP concentrations were 56.2 (48.0, 65.8) fmol/106 cells in non-pregnant versus 47.8 (40.4, 56.5) fmol/106 cells in pregnant women [geometric mean ratio (GMR, 95%CI): 0.85 (0.68, 1.06); p=0.15].

Conclusion

Steady-state TFV-DP concentrations in PBMCs were reassuringly not meaningfully different between pregnant and non-pregnant women.

DOI

10.1093/infdis/jiag460

PMID

42725863

Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.

Want more like this?

Browse more from the feed. A free account unlocks the full feed, saving and communities.

Back to the research feed

Create a free account · Sign in