Predicting Oral HIV Pre-Exposure Prophylaxis Efficacy in Cisgender Women Across Pregnancy and Postpartum

Authors

• Yifan Yu, University at Buffalo
• Kristina M. Brooks, University of Colorado-Anschutz Medical Campus
• Gustavo F. Doncel, Old Dominion UniversityFollow
• Brookie M. Best, University of California San Diego
• Mark A. Marzinke, Johns Hopkins University
• Mark Mirochnick, Boston University
• Peter L. Anderson, University of Colorado-Anschutz Medical Campus
• Landon Myer, University of Cape Town
• Connie Celum, University of Washington - Seattle Campus
• Renee Heffron, University Of Alabama at Birmingham
• Jenell Coleman, Johns Hopkins University
• Dvora L. Joseph Davey, University of Cape Town
• Lanxin Zhang, Robert-Koch Institute, Berlin
• Max von Kleist, Robert-Koch Institute, Berlin
• Craig W. Hendrix, Johns Hopkins University
• Jeremiah D. Momper, University of California San Diego, La Jolla
• Robert Bies, University at Buffalo
• Rachel K. Scott, Medstar Health

ORCID

0009-0009-9641-1325 (Doncel)

Document Type

Article

Publication Date

2026

DOI

10.1002/jcph.70278

Publication Title

The Journal of Clinical Pharmacology

Volume

66

Issue

9

Pages

e70278 (11 pp.)

Abstract

Cisgender women face an increased risk of HIV acquisition during pregnancy and postpartum. Oral pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is recommended in pregnancy despite limited published pharmacokinetic (PK) and efficacy data during pregnancy. Altered PK during pregnancy may reduce prophylactic efficacy and necessitate higher adherence. Tenofovir alafenamide (TAF) is a newer tenofovir prodrug with higher tenofovir diphosphate (TFV-DP) exposure in peripheral blood mononuclear cells (PBMCs), but the prophylactic efficacy of F/TAF across different reproductive stages in women is understudied. We adapted a multiscale modeling framework to predict the prophylactic efficacy of F/TDF and F/TAF across varying adherence levels and during the second trimester, third trimester, and 6-12 weeks postpartum. Clinical trial simulations were conducted utilizing PBMC TFV-DP and emtricitabine triphosphate concentrations as surrogate markers for F/TAF and F/TDF efficacy. For both F/TDF and F/TAF, prophylactic efficacy was lowest during the second trimester, increased in the third trimester (but remained below nonpregnant levels), and was highest postpartum. At high adherence levels of five or more pills per week, predicted effectiveness remained high across pregnancy and postpartum and effectiveness exceeded 97% for both regimens, with maximum decreases in the second trimester of only 0.9 percent point for F/TDF and 0.3 percent point for F/TAF. These findings suggest that adherence is the primary determinant of PrEP effectiveness during pregnancy and postpartum, while pregnancy-related PK changes have a limited impact on efficacy.

Rights

© 2026 The Authors.

This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Data Availability

Article states: "The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions."

Original Publication Citation

Yu, Y., Brooks, K. M., Doncel, G. F., Best, B. M., Marzinke, M. A., Mirochnick, M., Anderson, P. L., Myer, L., Celum, C., Heffron, R., Coleman, J., Davey, D. L. J., Zhang, L., von Kleist, M., Hendrix, C. W., Momper, J. D., Bies, R., & Scott, R. K. (2026). Predicting oral HIV pre-exposure prophylaxis efficacy in cisgender women across pregnancy and postpartum. The Journal of Clinical Pharmacology, 66(9), Article e70278. https://doi.org/10.1002/jcph.70278

Repository Citation

Yu, Y., Brooks, K. M., Doncel, G. F., Best, B. M., Marzinke, M. A., Mirochnick, M., Anderson, P. L., Myer, L., Celum, C., Heffron, R., Coleman, J., Davey, D. L. J., Zhang, L., von Kleist, M., Hendrix, C. W., Momper, J. D., Bies, R., & Scott, R. K. (2026). Predicting oral HIV pre-exposure prophylaxis efficacy in cisgender women across pregnancy and postpartum. The Journal of Clinical Pharmacology, 66(9), Article e70278. https://doi.org/10.1002/jcph.70278