Abstract |
Tenofovir disoproxil fumarate (TDF) is recommended as part of antiretroviral therapy (ART) for pregnant women with HIV and as monotherapy for pregnant women with hepatitis B virus (HBV) monoinfection at high risk of transmitting infection to their infants. Tenofovir (TFV) plasma exposures are reduced during pregnancy; however, concomitant antiretrovirals and the viral infection itself can also influence TFV pharmacokinetics. Our aim was to compare TFV pharmacokinetics in pregnant women receiving TDF-based ART, with or without a ritonavir-boosted protease inhibitor (r/PI), to pregnant women with HBV receiving TDF monotherapy. Non-r/PI regimens were primarily integrase strand transfer inhibitors or nonnucleoside reverse transcriptase inhibitor-based regimens. Data were combined from a pharmacokinetic study of pregnant women with HIV on ART (PANNA), and a study assessing TFV pharmacokinetics in pregnant women with HBV (iTAP). A total of 196 pregnant women, 59 with HIV (32 receiving r/PIs) and 137 with HBV monoinfection were included. Intraindividual TFV area under the plasma concentration-time curve from time 0 to 24 hours was 25%, 26%, and 21% lower during the third trimester compared to 1 month postpartum in women with HIV using TDF and an r/PI or TDF and non-r/PI and women with HBV receiving TDF monotherapy, respectively. TFV area under the plasma concentration-time curve from time 0 to 24 hours was similar in pregnant women receiving non-r/PI to pregnant women with HBV receiving TDF monotherapy (1.84 vs 1.86 µg • h/mL); however, pregnant women receiving TDF with an r/PI had higher exposures (2.41 µg • h/mL; P < .01). Pregnancy reduces TFV exposure and the relative size was not impacted by concomitant antiretroviral drugs or viral infection, but a drug-drug interaction between TDF and r/PI remains during pregnancy, leading to higher exposures than those on TDF and non-r/PI or TDF monotherapy.
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Authors | Vera E Bukkems, Elise J Smolders, Gonzague Jourdain, David M Burger, Angela P Colbers, Tim R Cressey, PANNA Network and iTAP Study Group |
Journal | Journal of clinical pharmacology
(J Clin Pharmacol)
Vol. 61
Issue 3
Pg. 388-393
(03 2021)
ISSN: 1552-4604 [Electronic] England |
PMID | 32960984
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Copyright | © 2020 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology. |
Chemical References |
- Anti-HIV Agents
- Reverse Transcriptase Inhibitors
- Tenofovir
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Topics |
- Adult
- Anti-HIV Agents
(administration & dosage, pharmacokinetics)
- Area Under Curve
- Drug Interactions
- Female
- HIV Infections
(drug therapy)
- Hepatitis B
(drug therapy)
- Humans
- Infectious Disease Transmission, Vertical
(prevention & control)
- Postpartum Period
- Pregnancy
- Pregnancy Complications, Infectious
(drug therapy, virology)
- Randomized Controlled Trials as Topic
- Retrospective Studies
- Reverse Transcriptase Inhibitors
(administration & dosage, pharmacokinetics)
- Tenofovir
(administration & dosage, pharmacokinetics)
- Young Adult
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