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HIV Med. 2015 Sep;16(8):502-11. doi: 10.1111/hiv.12252. Epub 2015 May 11.

Pharmacokinetics of tenofovir during pregnancy and postpartum.

Author information

1
School of Medicine-Rady Children's Hospital and Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
2
Harvard Medical School, Children's Hospital Boston, Boston, MA, USA.
3
Department of Preventive Medicine, Rush University Medical Center, Chicago, IL, USA.
4
Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, CA, USA.
5
Division of Epidemiology and Biostatistics, University of Arizona Mel & Enid Zuckerman College of Public Health, Tucson, AZ, USA.
6
Harvard School of Public Health, Center for Biostatistics in AIDS Research, Boston, MA, USA.
7
Social and Scientific Systems, Silver Springs, MD, USA.
8
Frontier Science & Technology Research Foundation, Amherst, NY, USA.
9
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), Bethesda, MD, USA.
10
National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
11
College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
12
Boston University School of Medicine, Boston, MA, USA.

Abstract

OBJECTIVES:

Tenofovir disoproxil fumarate (TDF) is increasingly used in the highly active antiretroviral therapy (HAART) regimens of pregnant women, but limited data exist on the pregnancy pharmacokinetics of chronically dosed TDF. This study described tenofovir pharmacokinetics during pregnancy and postpartum.

METHODS:

International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s is a prospective, nonblinded pharmacokinetic study of HIV-infected pregnant women that included a cohort receiving 300 mg TDF once daily. Steady-state 24-hour pharmacokinetic profiles were measured at the second and third trimesters, postpartum, and in maternal and umbilical cord samples collected at delivery. Tenofovir was measured by liquid chromatography-mass spectrometry (LC-MS). The target area under the concentration versus time curve from time 0 to 24 h post dose (AUC) was ≥ 1.99 μg h/mL (nonpregnant historical control 10th percentile).

RESULTS:

The median tenofovir AUC was decreased during the second (1.9 μg h/mL) and third (2.4 μg h/mL; P = 0.005) trimesters versus postpartum (3.0 μg h/mL). Tenofovir AUC exceeded the target for two of four women (50%) in the second trimester, 27 of 37 women [73%; 95% confidence interval (CI) 56%, 86%] in the third trimester, and 27 of 32 women (84%; 95% CI 67%, 95%) postpartum (P > 0.05). Median second/third-trimester troughs were lower (39/54 ng/mL) than postpartum (61 ng/mL). Median third-trimester weight was greater for subjects below the target AUC versus those above the target (97.9 versus 74.2 kg, respectively; P = 0.006). The median ratio of cord blood to maternal concentrations was 0.88. No infants were HIV infected.

CONCLUSIONS:

This study found lower tenofovir AUC and troughs during pregnancy. Transplacental passage with chronic TDF use during pregnancy was high. Standard TDF doses appear to be appropriate for most HIV-infected pregnant women but therapeutic drug monitoring with dose adjustment should be considered in pregnant women with high weight (> 90 kg) or inadequate HIV RNA response.

KEYWORDS:

HIV; antiretrovirals; pregnancy; prevention of perinatal transmission; tenofovir

PMID:
25959631
PMCID:
PMC4862736
DOI:
10.1111/hiv.12252
[Indexed for MEDLINE]
Free PMC Article

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