Tenofovir and tenofovir-diphosphate concentrations during pregnancy among HIV-uninfected women using oral preexposure prophylaxis

Maria Pyra, Peter L. Anderson, Craig Hendrix, Renee Heffron, Kenneth Mugwanya, Jessica E. Haberer, Katherine K. Thomas, Connie Celum, Deborah Donnell, Mark A Marzinke, Elizabeth A. Bukusi, Nelly R. Mugo, Stephen Asiimwe, Elly Katabira, Jared M. Baeten

Research output: Contribution to journalArticle

Abstract

Objectives: Pregnancy is a time of increased HIV acquisition risk and pregnancy reduces concentrations of antiretrovirals used for treatment. We assessed whether pregnancy lowers concentrations of tenofovir (TFV) and tenofovir-diphosphate (TFV-DP) among HIV-uninfected women using oral preexposure prophylaxis (PrEP). Methods: We analyzed data from an open-label PrEP study, comparing concentrations of TFV in plasma and TFV-DP in dried blood spots (DBS) among 37 pregnant women and 97 nonpregnant women. Analyses controlled for adherence from daily electronic monitoring. Results: The average plasma concentration of TFV among pregnant women was 34.7 ng/ml with 22.2 average recorded doses over the prior month versus 86.5 ng/ml with 23.1 doses among nonpregnant women. After controlling for adherence, TFV concentrations were 58% lower among pregnant women, a statistically significant difference of 50.4 ng/ml (95% CI 68.3 to 32.5). The average TFV-DP concentration was 450.3 fmol/punch among pregnant women and 636.7 fmol/punch among nonpregnant women. This difference was not statistically significant after adjusting for adherence; however, among those with quantifiable TFV-DP, concentrations were 27% lower during pregnancy [202 fmol/punch (95% CI 384 to 19)]. Among participants with samples before and during pregnancy, there were significant decreases during pregnancy, controlling for adherence: 28.1 ng/ml TFV (95% CI 52.3 to 4.0) and 289.2 fmol/punch TFV-DP (95% CI 439.0 to 139.3). Conclusion: Consistent with studies among HIV-infected women on ART, we found TFV and TFV-DP concentrations were lower during pregnancy. There is no established TFV concentration threshold to achieve HIV prevention. Additional pharmacokinetic studies and studies of PrEP efficacy in pregnancy are needed.

Original languageEnglish (US)
Pages (from-to)1891-1898
Number of pages8
JournalAIDS
Volume32
Issue number13
DOIs
Publication statusPublished - Jan 1 2018

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Keywords

  • HIV
  • Preexposure prophylaxis
  • Pregnancy
  • Tenofovir

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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