Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women
Angela Colbers, Brookie Best, Stein Schalkwijk, Jiajia Wang, Alice Stek, Carmen Hidalgo Tenorio, David Hawkins, Graham Taylor, Regis Kreitchmann, Sandra Burchett, Annette Haberl, Kabamba Kabeya, Marjo van Kasteren, Elizabeth Smith, Edmund Capparelli, David Burger, Mark Mirochnick, PANNA Network and the IMPAACT 1026 Study Team, M E van der Ende, A J A M van der Ven, J Nellen, J Moltó, I Pujol, A Antinori, E Nicastri, C Giaquinto, K Weizsäcker, A Gingelmaier, F Lyons, J Lambert, C Wyen, G Faetkenheuer, J K Rockstroh, C Schwarze-Zander, S Tariq Sadiq, Y Gilleece, C Wood, Shelley Buschur, Chivon Jackson, Mary Paul, Claudia Florez, Monica Stone, Mindy Katz, Raphaelle Auguste, Andrew Wiznia, Karen L Bruder, Gail Lewis, Denise Casey, Marcelo H Losso, Silvina A Ivalo, Alejandro Hakim, Audra Deveikis, Jagmohan Batra, Jackson Alvarez, Katherine M Knapp, Nina Sublette, Thomas Wride, Irma L Febo, Ruth Santos, Vivian Tamayo, Angela Colbers, Brookie Best, Stein Schalkwijk, Jiajia Wang, Alice Stek, Carmen Hidalgo Tenorio, David Hawkins, Graham Taylor, Regis Kreitchmann, Sandra Burchett, Annette Haberl, Kabamba Kabeya, Marjo van Kasteren, Elizabeth Smith, Edmund Capparelli, David Burger, Mark Mirochnick, PANNA Network and the IMPAACT 1026 Study Team, M E van der Ende, A J A M van der Ven, J Nellen, J Moltó, I Pujol, A Antinori, E Nicastri, C Giaquinto, K Weizsäcker, A Gingelmaier, F Lyons, J Lambert, C Wyen, G Faetkenheuer, J K Rockstroh, C Schwarze-Zander, S Tariq Sadiq, Y Gilleece, C Wood, Shelley Buschur, Chivon Jackson, Mary Paul, Claudia Florez, Monica Stone, Mindy Katz, Raphaelle Auguste, Andrew Wiznia, Karen L Bruder, Gail Lewis, Denise Casey, Marcelo H Losso, Silvina A Ivalo, Alejandro Hakim, Audra Deveikis, Jagmohan Batra, Jackson Alvarez, Katherine M Knapp, Nina Sublette, Thomas Wride, Irma L Febo, Ruth Santos, Vivian Tamayo
Abstract
Objective: To describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)-infected women during pregnancy and post partum.
Methods: HIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated.
Results: Eighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval, .60-.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58-0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03-0.56). The viral load close to delivery was <50 copies/mL in 13 women (76%). All children were HIV negative at testing.
Conclusions: Overall maraviroc exposure during pregnancy was decreased, with a reduction in AUCtau and maximum concentration of about 30%. Ctrough was reduced by 15% but exceeded the minimum Ctrough target concentration. Therefore, the standard adult dose seems sufficient in pregnancy.
Clinical trials registration: NCT00825929 and NCT000422890.
Trial registration: ClinicalTrials.gov NCT00422890 NCT00825929.
Keywords: HIV; MTCT; maraviroc; pharmacokinetics; pregnancy.
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Source: PubMed