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: Kelly E 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, Helen McIlleron, TSHEPISO Study Team
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 211 Issue 2 Pg. 197-205 (Jan 15 2015) ISSN: 1537-6613 [Electronic] United States
• PMID: 25081933 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Alkynes
• Anti-HIV Agents
• Benzoxazines
• Cyclopropanes
• efavirenz

Topics

• Adolescent
• Adult
• Alkynes
• Anti-HIV Agents (administration & dosage, pharmacokinetics)
• Benzoxazines (administration & dosage, pharmacokinetics)
• Cohort Studies
• Coinfection (drug therapy, virology)
• Cyclopropanes
• Female
• HIV Infections (complications, drug therapy, virology)
• HIV-1 (isolation & purification)
• Humans
• Plasma (chemistry, virology)
• Pregnancy
• Pregnancy Complications, Infectious (drug therapy, virology)
• Prospective Studies
• South Africa
• Tuberculosis (complications)
• Viral Load
• Young Adult