Dataset Information

Plasma concentrations, efficacy and safety of efavirenz in HIV-infected adults treated for tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA trial).

ABSTRACT:

Objective

To assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients.

Methods

HIV-infected adults with CD4+ T cell count ? 200/mm(3) received standard 6-month tuberculosis treatment and antiretroviral therapy including a daily-dose of 600 mg of efavirenz, irrespective of their body weight. Mid-dose blood samples were drawn both on tuberculosis treatment (week +2 and week +6 after antiretroviral therapy initiation, and week 22 of follow-up) and off tuberculosis treatment (week 50 of follow-up). Considered therapeutic range was 1,000 to 4,000 ng/mL. Multivariate analysis was performed to evaluate the association between efavirenz concentration below 1,000 ng/mL and virological failure. Linear regression was used to test the association between efavirenz exposure and CD4+ T cell gain. Severe side effects potentially related to efavirenz were described and their association with efavirenz exposure was tested by multivariate analysis.

Results

Efavirenz plasma concentrations were available in 540 patients. Median [interquartile range] efavirenz concentrations were 2,674 ng/mL [1,690-4,533], 2,667 ng/mL [1,753-4,494] and 2,799 ng/mL [1,804-4,744] at week +2, week +6, week 22, respectively, and 2,766 ng/mL [1,941-3,976] at week 50. Efavirenz concentrations were lower at week 50 (off rifampicin) compared to week 22 (on rifampicin) (p<0.001). Late attendance to study visit and low hemoglobinemia were the only factors associated with an increased risk of efavirenz concentration below 1,000 ng/mL. Efavirenz concentration below 1,000 ng/mL was not associated with treatment failure. Efavirenz concentration above 4,000 ng/mL was associated with higher risk of central nervous system side effects (p<0.001) and of hepatotoxicity (p<0.001).

Conclusion

Body weight and tuberculosis treatment were not associated with low efavirenz concentrations or treatment failure, supporting the 600 mg daily-dose of efavirenz in HIV-tuberculosis co-infected patients. High efavirenz concentrations were related to a higher risk of central nervous system side effects and hepatotoxicity.

Trial registration

ClinicalTrials.gov NCT01300481.

SUBMITTER: Borand L

PROVIDER: S-EPMC3946522 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Plasma concentrations, efficacy and safety of efavirenz in HIV-infected adults treated for tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA trial).

Borand Laurence L Madec Yoann Y Laureillard Didier D Chou Monidarin M Marcy Olivier O Pheng Phearavin P Prak Narom N Kim Chindamony C Lak Khemarin Kim KK Hak Chanroeun C Dim Bunnet B Nerrienet Eric E Fontanet Arnaud A Sok Thim T Goldfeld Anne E AE Blanc François-Xavier FX Taburet Anne-Marie AM

PloS one 20140307 3

<h4>Objective</h4>To assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients.<h4>Methods</h4>HIV-infected adults with CD4+ T cell count ≤ 200/mm(3) received standard 6-month tuberculosis treatment and antiretroviral therapy including a daily-dose of 600 mg of efavirenz, irrespective of their body weight. Mid-dose blood samples were drawn both on tuberculosis treatment (week +2 and week + ...[more]

PMID: 24608960

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Dataset Information

Plasma concentrations, efficacy and safety of efavirenz in HIV-infected adults treated for tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA trial).

Objective

Methods

Results

Conclusion

Trial registration

Publications

Plasma concentrations, efficacy and safety of efavirenz in HIV-infected adults treated for tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA trial).

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