title: Pharmacokinetics of efavirenz and treatment of HIV-1 among pregnant women with and without tuberculosis coinfection.
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.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Dooley
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town.
authors.forename: Paolo
authors.initials: P
authors.lastname: Denti
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland Perinatal HIV Research Unit, University of the Witwatersrand.
authors.forename: Neil
authors.initials: N
authors.lastname: Martinson
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cohn
authors.affiliation: Perinatal HIV Research Unit, University of the Witwatersrand.
authors.forename: Fildah
authors.initials: F
authors.lastname: Mashabela
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hoffmann
authors.affiliation: Vanderbilt University, Nashville, Tennessee.
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
authors.affiliation: Department of Obstetrics, Chris Hani Baragwanath Hospital and University of the Witwatersrand, Soweto, South Africa.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hull
authors.affiliation: Perinatal HIV Research Unit, University of the Witwatersrand.
authors.forename: Regina
authors.initials: R
authors.lastname: Msandiwa
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town.
authors.forename: Sandra
authors.initials: S
authors.lastname: Castel
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town.
authors.forename: Lubbe
authors.initials: L
authors.lastname: Wiesner
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chaisson
authors.forename: Helen
authors.initials: H
authors.lastname: McIlleron
mesh_terms: D000293:Adolescent; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D048588:Benzoxazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015331:Cohort Studies; D060085:Coinfection / Q000188:drug therapy / Q000821:virology; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D010949:Plasma / Q000737:chemistry / Q000821:virology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D011446:Prospective Studies; D013019:South Africa; D014376:Tuberculosis / Q000150:complications; D019562:Viral Load; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz
keywords: HIV/tuberculosis co-infection; efavirenz; isoniazid preventive therapy; pharmacogenetics; population pharmacokinetics; pregnancy; rifampin
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