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

Kelly Elise Dooley, Paolo Denti, Neil Martinson, Silvia Cohn, Fildah Mashabela, Jennifer Hoffmann, David W. Haas, Jennifer Hull, Regina Msandiwa, Sandra Castel, Lubbe Wiesner, Richard E Chaisson

Research output: Contribution to journalArticle

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 min. 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

Original languageEnglish (US)
Pages (from-to)197-205
Number of pages9
JournalJournal of Infectious Diseases
Volume211
Issue number2
DOIs
StatePublished - Jan 15 2015

Fingerprint

efavirenz
Coinfection
HIV-1
Pregnant Women
Tuberculosis
Pharmacokinetics
Mothers
Viral Load
Pregnancy
Postpartum Period
Therapeutics
HIV
Isoniazid
South Africa

Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Pharmacokinetics of efavirenz and treatment of HIV-1 among pregnant women with and without tuberculosis coinfection. / Dooley, Kelly Elise; Denti, Paolo; Martinson, Neil; Cohn, Silvia; Mashabela, Fildah; Hoffmann, Jennifer; Haas, David W.; Hull, Jennifer; Msandiwa, Regina; Castel, Sandra; Wiesner, Lubbe; Chaisson, Richard E.

In: Journal of Infectious Diseases, Vol. 211, No. 2, 15.01.2015, p. 197-205.

Research output: Contribution to journalArticle

Dooley, KE, Denti, P, Martinson, N, Cohn, S, Mashabela, F, Hoffmann, J, Haas, DW, Hull, J, Msandiwa, R, Castel, S, Wiesner, L & Chaisson, RE 2015, 'Pharmacokinetics of efavirenz and treatment of HIV-1 among pregnant women with and without tuberculosis coinfection', Journal of Infectious Diseases, vol. 211, no. 2, pp. 197-205. https://doi.org/10.1093/infdis/jiu429
Dooley, Kelly Elise ; Denti, Paolo ; Martinson, Neil ; Cohn, Silvia ; Mashabela, Fildah ; Hoffmann, Jennifer ; Haas, David W. ; Hull, Jennifer ; Msandiwa, Regina ; Castel, Sandra ; Wiesner, Lubbe ; Chaisson, Richard E. / Pharmacokinetics of efavirenz and treatment of HIV-1 among pregnant women with and without tuberculosis coinfection. In: Journal of Infectious Diseases. 2015 ; Vol. 211, No. 2. pp. 197-205.
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AU - Denti, Paolo

AU - Martinson, Neil

AU - Cohn, Silvia

AU - Mashabela, Fildah

AU - Hoffmann, Jennifer

AU - Haas, David W.

AU - Hull, Jennifer

AU - Msandiwa, Regina

AU - Castel, Sandra

AU - Wiesner, Lubbe

AU - Chaisson, Richard E

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AB - 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 min. 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

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