The impact of pregnancy on efavirenz (EFV) pharmacokinetics is unknown.
International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is an on-going, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving 600 mg EFV once daily as part of combination antiretroviral therapy. Intensive steady-state 24-hour blood sampling was performed during the third trimester and at 6–12 weeks postpartum. Maternal and umbilical cord blood samples were drawn at delivery. Pharmacokinetics targets were the estimated 10th percentile EFV area under the curve (AUC) in nonpregnant historical controls (40.0 mcg·hr−1·mL−1) and a trough concentration of 1 mcg/mL.
Twenty-five women were enrolled during the third trimester: median (range) age was 29.3 (18.9–42.9) years, weight 69.0 (40–130) kg, and gestational age 32.9 (30.1–38.7) weeks. Median (range) EFV AUC0–24, Cmax, and C24 hours were 55.4 mcg·hr−1·mL−1 (13.5-220.3), 5.4 mcg/mL (1.9–12.2), and 1.6 mcg/mL (0.23–8.13), respectively. EFV AUC and Cmax did not differ during pregnancy and postpartum but C24 hours was lower during the third trimester (1.6 vs. 2.1 mcg/mL, P = 0.01). During the third trimester, 5 of 25 (20%) women had an EFV AUC below the target and 3 of 25 (12%) had a trough concentration below 1 mcg/mL. EFV cord blood/maternal concentration ratio was 0.49 (0.37–0.74). All women had a HIV-1 RNA viral load less than 400 copies per milliliter at delivery and 19 (76%) had a viral load below 50 copies per milliliter. One child was perinatally HIV infected. Three women were exposed to EFV throughout the first 6 weeks of pregnancy. EFV was well tolerated, and among the 25 infants, no congenital anomalies or newborn complications were reported.
Changes in EFV pharmacokinetics during pregnancy compared with postpartum are not sufficiently large enough to warrant a dose adjustment during pregnancy.
*Program for HIV Prevention and Treatment (IRD URI 174), Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
†Harvard School of Public Health, Department of Immunology & Infectious Diseases, Boston, MA, USA
‡Institut de Recherché pour le Développement (IRD), UMI 174-Program for HIV Prevention and Treatment, Marseille, France
§University of Southern California School of Medicine, Department of Obstetrics and Gynecology, Los Angeles, CA
‖University of California San Diego School of Medicine and Skaggs School of Pharmacy & Pharmaceutical Sciences, San Diego, CA
¶Chonburi Hospital, Department of Internal Medicine, Chonburi, Thailand
#Bhumibol Adulyadej Hospital, Department of Obstetrics and Gynecology, Bangkok, Thailand
**Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand
††Prapokklao Hospital, Department of Obstetrics and Gynecology, Chantaburi, Thailand
‡‡Siriraj Hospital, Department of Obstetrics and Gynecology, Bangkok, Thailand
§§Statistical & Data Analysis Center, Harvard School of Public Health, Department of Immunology & Infectious Diseases, Boston, MA, USA
‖‖National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD
¶¶Boston University School of Medicine, Boston, MA.
Correspondence to: Tim R. Cressey, PhD, Program for HIV Prevention and Treatment Institut de Recherché pour le Développement-Program for HIV Prevention and Treatment 174 Department of Medical Technology, Faculty of Associated Medical Sciences, Department of Medical Technology, 6th Floor, 110 Inthawaroros Road, Muang Chiang Mai 50200, Thailand (e-mail: email@example.com).
Supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the International Maternal Pediatric Adolescent AIDS Clinical Trials Group Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group was provided by the National Institute of Allergy and Infectious Diseases (U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health (AI068632)
Presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI), February 27 to March 02, 2011, Boston, MA. Astract #754.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health.
The authors have no conflicts of interest to disclose.
The members of the IMPAACT P1026s team are listed in Appendix I.
Received August 31, 2011
Accepted November 1, 2011