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J Infect Dis. 2015 Jan 15;211(2):197-205. doi: 10.1093/infdis/jiu429. Epub 2014 Jul 31.

Pharmacokinetics of efavirenz and treatment of HIV-1 among pregnant women with and without tuberculosis coinfection.

Author information

1
Johns Hopkins University School of Medicine, Baltimore, Maryland.
2
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town.
3
Johns Hopkins University School of Medicine, Baltimore, Maryland Perinatal HIV Research Unit, University of the Witwatersrand.
4
Perinatal HIV Research Unit, University of the Witwatersrand.
5
Vanderbilt University, Nashville, Tennessee.
6
Department of Obstetrics, Chris Hani Baragwanath Hospital and University of the Witwatersrand, Soweto, South Africa.

Erratum in

Abstract

BACKGROUND:

Pregnancy and tuberculosis treatment or prophylaxis can affect efavirenz pharmacokinetics, maternal human immunodeficiency virus type 1 (HIV-1) treatment outcomes, and mother-to-child transmission (MTCT) risk.

METHODS:

We evaluated a prospective cohort of pregnant, HIV-infected women with and without tuberculosis in Soweto, South Africa. Pharmacokinetic sampling was performed at gestation week 37 and during the postpartum period. Efavirenz trough concentrations (Cmin) were predicted using population pharmacokinetic models. HIV-viral load was measured at delivery for mothers and at 6 weeks of age for infants.

RESULTS:

Ninety-seven women participated; 44 had tuberculosis. Median efavirenz Cmin during pregnancy was 1.35 µg/mL (interquartile range [IQR], 0.90-2.07 µg/mL; 27% had an efavirenz Cmin of < 1 µg/mL), compared with a median postpartum value of 2.00 µg/mL (IQR, 1.40-3.59 µg/mL; 13% had an efavirenz Cmin of < 1 µg/mL). A total of 72% of pregnant women with extensive CYP2B6 genotypes had an efavirenz Cmin of <1 µg/mL. Rifampin did not reduce the efavirenz Cmin. Isoniazid (for prophylaxis or treatment), though, reduced the rate of efavirenz clearance. At delivery, median durations of ART were 13 weeks (IQR, 9-18 weeks) and 21 weeks (IQR, 13-64 weeks) for women with and those without tuberculosis, respectively; 55% and 83%, respectively, had a viral load of <20 copies/mL (P = .021). There was 1 case of MTCT.

CONCLUSIONS:

Pregnancy increased the risk of low efavirenz concentrations, but MTCT was rare. A detectable HIV-viral load at delivery was more common among pregnant women with tuberculosis, in whom ART was generally initiated later.

KEYWORDS:

HIV/tuberculosis co-infection; efavirenz; isoniazid preventive therapy; pharmacogenetics; population pharmacokinetics; pregnancy; rifampin

PMID:
25081933
PMCID:
PMC4334832
DOI:
10.1093/infdis/jiu429
[Indexed for MEDLINE]
Free PMC Article

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