TY - JOUR
T1 - Plasma concentrations, efficacy and safety of efavirenz in HIV-infected adults treated for tuberculosis in cambodia (ANRS 1295-CIPRA KH001 CAMELIA Trial)
AU - Borand, Laurence
AU - Madec, Yoann
AU - Laureillard, Didier
AU - Chou, Monidarin
AU - Marcy, Olivier
AU - Pheng, Phearavin
AU - Prak, Narom
AU - Kim, Chindamony
AU - Lak, Khemarin Kim
AU - Hak, Chanroeun
AU - Dim, Bunnet
AU - Nerrienet, Eric
AU - Fontanet, Arnaud
AU - Sok, Thim
AU - Goldfeld, Anne E.
AU - Blanc, François Xavier
AU - Taburet, Anne Marie
PY - 2014/3/7
Y1 - 2014/3/7
N2 - 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/mm3 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 [1,6904,533], 2,667 ng/mL [1,7534,494] and 2,799 ng/mL [1,8044,744] at week +2, week +6, week 22, respectively, and 2,766 ng/mL [1,9413,976] at week 50. Efavirenz concentrations were lower at week 50 (off rifampicin) compared to week 22 (on rifampicin) (<,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 (<,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.
AB - 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/mm3 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 [1,6904,533], 2,667 ng/mL [1,7534,494] and 2,799 ng/mL [1,8044,744] at week +2, week +6, week 22, respectively, and 2,766 ng/mL [1,9413,976] at week 50. Efavirenz concentrations were lower at week 50 (off rifampicin) compared to week 22 (on rifampicin) (<,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 (<,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.
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U2 - 10.1371/journal.pone.0090350
DO - 10.1371/journal.pone.0090350
M3 - Article
C2 - 24608960
AN - SCOPUS:84897557685
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 3
M1 - e90350
ER -