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

Year: 2026

Type: article

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.

Source: The Journal of Clinical Pharmacology

DOI: 10.1002/jcph.70278

Authors: Yifan Yu, Kristina M. Brooks, Gustavo F. Doncel, Brookie M. Best, Mark A. Marzinke, Mark Mirochnick, Peter L. Anderson, Landon Myer, Connie Celum, Renee Heffron, Jenell Coleman, Dvora L. Joseph Davey, Lanxin Zhang, Max von Kleist, Craig W. Hendrix, Jeremiah D. Momper, Robert Bies, Rachel K. Scott

Institutions: University at Buffalo, State University of New York, University of Colorado Anschutz, Eastern Virginia Medical School, Old Dominion University, University of California San Diego, Rady Children's Hospital-San Diego, Johns Hopkins University, Boston University, University of Cape Town, University of Washington, University of Alabama at Birmingham, UAB Medicine, University of California, Los Angeles, Robert Koch Institute, Georgetown University

Language: English

Topic: HIV/AIDS Research and Interventions

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,150

Funders: United States Agency for International Development, Gilead Sciences, U.S. President’s Emergency Plan for AIDS Relief, Eastern Virginia Medical School, International Maternal Pediatric Adolescent AIDS Clinical Trials Network, Deutsche Forschungsgemeinschaft, National Institutes of Health, Center for AIDS Research, University of Washington, University of North Carolina at Chapel Hill, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development

OpenAlex ID: W7207847987