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

Maria Pyra; Peter L. Anderson; Craig W. 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

doi:10.1097/QAD.0000000000001922

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

Maria Pyra, Peter L. Anderson, Craig W. 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^*

^*Corresponding author for this work

Medical Social Sciences

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

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 language	English (US)
Pages (from-to)	1891-1898
Number of pages	8
Journal	AIDS
Volume	32
Issue number	13
DOIs	https://doi.org/10.1097/QAD.0000000000001922
State	Published - 2018

Funding

The Partners Demonstration Project was funded by the National Institute of Mental Health of the US National Institutes of Health (R01 MH095507), the Bill & Melinda Gates Foundation (OPP1056051), and the US Agency for International Development (AID-OAA-A-12-00023). This analysis was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (TL1 TR002318). Research reported in this publication was supported by the UW/Fred Hutch Center for AIDS Research, funded by NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK of the National Institutes of Health under award number P30 A1027757 and the HIV Prevention Trials Network (UM1 AI068613). The contents are the responsibility of the authors and do not necessarily reflect the views of USAID, NIH, or the United States Government. Funding: The Partners Demonstration Project was funded by the National Institute of Mental Health of the US National Institutes of Health (R01 MH095507), the Bill & Melinda Gates Foundation (OPP1056051), and the US Agency for International Development (AID-OAA-A-12-00023). This analysis was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (TL1 TR002318). Research reported in this publication was supported by the UW/Fred Hutch Center for AIDS Research, funded by NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK of the National Institutes of Health under award number P30 A1027757 and the HIV Prevention Trials Network (UM1 AI068613). The contents are the responsibility of the authors and do not necessarily reflect the views of USAID, NIH, or the United States Government.

Keywords

HIV
Preexposure prophylaxis
Pregnancy
Tenofovir

ASJC Scopus subject areas

Infectious Diseases
Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/QAD.0000000000001922

Cite this

Pyra, M., Anderson, P. L., Hendrix, C. W., Heffron, R., Mugwanya, K., Haberer, J. E., Thomas, K. K., Celum, C., Donnell, D., Marzinke, M. A., Bukusi, E. A., Mugo, N. R., Asiimwe, S., Katabira, E., & Baeten, J. M. (2018). Tenofovir and tenofovir-diphosphate concentrations during pregnancy among HIV-uninfected women using oral preexposure prophylaxis. AIDS, 32(13), 1891-1898. https://doi.org/10.1097/QAD.0000000000001922

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

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.",

keywords = "HIV, Preexposure prophylaxis, Pregnancy, Tenofovir",

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

year = "2018",

doi = "10.1097/QAD.0000000000001922",

language = "English (US)",

volume = "32",

pages = "1891--1898",

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issn = "0269-9370",

publisher = "Lippincott Williams and Wilkins",

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Pyra, M, Anderson, PL, Hendrix, CW, Heffron, R, Mugwanya, K, Haberer, JE, Thomas, KK, Celum, C, Donnell, D, Marzinke, MA, Bukusi, EA, Mugo, NR, Asiimwe, S, Katabira, E & Baeten, JM 2018, 'Tenofovir and tenofovir-diphosphate concentrations during pregnancy among HIV-uninfected women using oral preexposure prophylaxis', AIDS, vol. 32, no. 13, pp. 1891-1898. https://doi.org/10.1097/QAD.0000000000001922

TY - JOUR

T1 - Tenofovir and tenofovir-diphosphate concentrations during pregnancy among HIV-uninfected women using oral preexposure prophylaxis

AU - Pyra, Maria

AU - Anderson, Peter L.

AU - Hendrix, Craig W.

AU - Heffron, Renee

AU - Mugwanya, Kenneth

AU - Haberer, Jessica E.

AU - Thomas, Katherine K.

AU - Celum, Connie

AU - Donnell, Deborah

AU - Marzinke, Mark A.

AU - Bukusi, Elizabeth A.

AU - Mugo, Nelly R.

AU - Asiimwe, Stephen

AU - Katabira, Elly

AU - Baeten, Jared M.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - HIV

KW - Preexposure prophylaxis

KW - Pregnancy

KW - Tenofovir

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AN - SCOPUS:85056409986

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VL - 32

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JO - AIDS

JF - AIDS

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ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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