Plasma concentrations of efavirenz with a 600 mg standard dose in Cambodian HIV-infected adults treated for tuberculosis with a body weight above 50 kg.

Abstract

BACKGROUND:

The optimal dose of efavirenz for HIV-infected patients receiving a tuberculosis regimen including rifampicin remains debated, especially for subjects weighing over 50 kg. To address this issue, we measured plasma efavirenz concentrations from Cambodian adults with tuberculosis enrolled in the CAMELIA randomized trial (ClinicalTrials.gov number, NCT01300481) 6 weeks after the onset of antiretroviral therapy.

METHODS:

Efavirenz concentrations and proportions of patients with concentrations below 1,000 ng/ml were compared across patient body weight below or above 50 kg using a Student's t-test and a χ(2) test, respectively. Factors associated with efavirenz concentrations below 1,000 ng/ml were identified by logistic regression analysis. Logistic regression analysis was also performed to check if efavirenz concentrations below 1,000 ng/ml were associated with virological failure.

RESULTS:

Plasma efavirenz concentrations were higher in the 332 patients who weighed <50 kg compared with the 150 who weighed ≥50 kg (median [IQR] 2,859 [1,787-4,749] and 2,060 [1,425-3,575] ng/ml, respectively; P=0.02). However, the proportion of patients with efavirenz concentrations below 1,000 ng/ml was not different between those weighing less than or more than 50 kg (6% and 10%, respectively; P=0.13) and a body weight above 50 kg was not associated with a higher risk of plasma efavirenz concentrations below 1,000 ng/ml. When plasma efavirenz concentrations below 1,000 ng/ml were present, they were not associated with virological failure.

CONCLUSIONS:

The current WHO guidelines recommending 600 mg efavirenz daily irrespective of patient's body weight remains a safe and effective approach to treating coinfected adults needing simultaneous tuberculosis and HIV therapy.

• Authors: Laurence Borand, Didier Laureillard, Yoann Madec, Monidarin Chou, Phearavin Pheng, Olivier Marcy, Thim Sok, Anne E Goldfeld, Anne-Marie Taburet, François-Xavier Blanc, CAMELIA ANRS 1295-CIPRA KH001 Study Team
• Journal: Antiviral therapy (Antivir Ther) Vol. 18 Issue 3 Pg. 419-23 ( 2013) ISSN: 2040-2058 [Electronic] England
• PMID: 23237982 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Anti-HIV Agents
• Antibiotics, Antitubercular
• Benzoxazines
• Cyclopropanes
• efavirenz

Topics

• Alkynes
• Anti-HIV Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Antibiotics, Antitubercular (therapeutic use)
• Benzoxazines (administration & dosage, pharmacokinetics, therapeutic use)
• Body Weight
• Coinfection
• Cyclopropanes
• HIV Infections (complications, drug therapy, virology)
• Humans
• Tuberculosis (complications, drug therapy)
• Viral Load