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Antimicrobial Agents and Chemotherapy, June 2009, p. 2367-2374, Vol. 53, No. 6
0066-4804/09/$08.00+0 doi:10.1128/AAC.01523-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Genital Tract, Cord Blood, and Amniotic Fluid Exposures of Seven Antiretroviral Drugs during and after Pregnancy in Human Immunodeficiency Virus Type 1-Infected Women
Rosa F. Yeh,1,
Naser L. Rezk,1
Angela D. M. Kashuba,1
Julie B. Dumond,1,
Hiba L. Tappouni,1,
Hsiao-Chuan Tien,2
Ya-Chi Chen,1,¶
Manoli Vourvahis,1,||
Amanda L. Horton,3
Susan A. Fiscus,4 and
Kristine B. Patterson4*
School of Pharmacy,1 FPG Institute,2 Department of Obstetrics and Gynecology,3 School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina4
Received 14 November 2008/ Returned for modification 20 January 2009/ Accepted 16 March 2009
The objective of the study was to measure antiretroviral exposures in four physiological compartments during pregnancy, delivery, and postpartum. This prospective, open-label, longitudinal study collected paired blood plasma (BP) and genital tract (GT) aspirates antepartum, at delivery, and up to 12 weeks postpartum. Antiretroviral cord BP and amniotic fluid concentrations were also measured. Drug concentrations were analyzed by validated high-performance liquid chromatography/UV and liquid chromatography/tandem mass spectrometry methods, with secondary compartment concentrations presented as the percentage of BP. Fourteen women taking lamivudine plus zidovudine and either lopinavir-ritonavir (n = 7), nelfinavir (n = 6), or nevirapine (n = 1) were enrolled; four also received tenofovir. GT penetration relative to BP was highest for the nucleoside reverse transcriptase inhibitors compared to the protease inhibitors and nevirapine. Only antepartum nelfinavir GT penetration was significantly higher than in the second trimester (geometric mean ratio [GMR], 179.3) or third trimester (GMR, 41.9). Compared to nonpregnant historical controls, antepartum GT penetration was significantly lower (P < 0.05) for zidovudine (GMR, 0.25) and lopinavir (GMR, 0.03); postpartum lopinavir GT penetration continued to be significantly lower (GMR, 0.27). Cord BP exposures were highest for lamivudine and tenofovir (
100%), with cord BP levels of the remaining drugs ranging from 49 to 86% of that of the respective BP level. Amniotic exposures for lamivudine, zidovudine, tenofovir, and nelfinavir were 100%, nevirapine exposure was 53%, and lopinavir and ritonavir exposures were 
6% that of BP. We conclude that GT, cord BP, and amniotic fluid exposures vary within and between antiretroviral drug classes and biologic sites. Measurement of antiretroviral exposure in maternal genital secretions, cord BP, and amniotic fluid may be needed to identify signals of subtherapeutic or supratherapeutic drug exposure.
* Corresponding author. Mailing address: AIDS Clinical Trials Unit, 130 Mason Farm Rd., CB 7215, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. Phone: (919) 843-2544. Fax: (919) 966-8928. E-mail: kristine_patterson{at}med.unc.edu
Published ahead of print on 23 March 2009.
Current address: University of Houston College of Pharmacy, 1400 Moursund St., Ste. 318, Houston, TX 77030.
Current address: East Tennessee State University College of Pharmacy, Box 70657, Johnson City, TN 37614-1701.
Current address: GlaxoSmithKline, Research Triangle Park, NC.
¶ Current address: Forest Research Institute, Forest Laboratories, Inc., Harborside Financial Center, Plaza V, Jersey City, NJ 07311.
|| Current address: Pfizer Global Research and Development, 50 Pequot Avenue, New London, CT 06320.
Antimicrobial Agents and Chemotherapy, June 2009, p. 2367-2374, Vol. 53, No. 6
0066-4804/09/$08.00+0 doi:10.1128/AAC.01523-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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