OBJECTIVES:Nevirapine (NVP), a still widely used nonnucleoside reverse transcriptase inhibitor, can cause severe hepatotoxicity. Previous studies suggest that CD4 cell counts more than 250 cells per microliter in women and more than 400 cells per microliter in men are risk factors for NVP-related hepatotoxicity. These studies have informed Chinese national treatment guidelines. We evaluate whether current Chinese guidelines for NVP use are appropriate. METHODS:Longitudinal data were pooled from 2 clinical trials between 2005 and 2009 across mainland China. Five hundred sixty-six antiretroviral therapy-naive Chinese patients were given NVP-containing antiretroviral therapy for 24 weeks. Hepatotoxicity was defined as alanine aminotransferase, aspartate transaminase, or total bilirubin level greater than 1.25 times the upper limit of normal range. Severe hepatotoxicity was defined as greater than 5 times the upper limit of normal range. RESULTS:One hundred ninety-seven (36.1%) patients developed hepatotoxicity during treatment, including 42 (7.7%) patients with severe hepatotoxicity. CD4 cell count more than 250 cells per microliter was an independent predictor for hepatotoxicity both in men [relative risk = 1.22 (95% confidence interval: 1.04 to 1.44)] and in women [relative risk = 1.72 (95% confidence interval: 1.20 to 2.46)]. Severe hepatotoxicity was also more common among all persons with CD4 >250 cells per microliter. CONCLUSIONS:Hepatotoxicity was a common adverse effect of NVP among men and women with CD4 >250 cells per microliter. Chinese treatment guidelines should be considered to reflect this risk.
RCT Entities:
OBJECTIVES:Nevirapine (NVP), a still widely used nonnucleoside reverse transcriptase inhibitor, can cause severe hepatotoxicity. Previous studies suggest that CD4 cell counts more than 250 cells per microliter in women and more than 400 cells per microliter in men are risk factors for NVP-related hepatotoxicity. These studies have informed Chinese national treatment guidelines. We evaluate whether current Chinese guidelines for NVP use are appropriate. METHODS: Longitudinal data were pooled from 2 clinical trials between 2005 and 2009 across mainland China. Five hundred sixty-six antiretroviral therapy-naive Chinese patients were given NVP-containing antiretroviral therapy for 24 weeks. Hepatotoxicity was defined as alanine aminotransferase, aspartate transaminase, or total bilirubin level greater than 1.25 times the upper limit of normal range. Severe hepatotoxicity was defined as greater than 5 times the upper limit of normal range. RESULTS: One hundred ninety-seven (36.1%) patients developed hepatotoxicity during treatment, including 42 (7.7%) patients with severe hepatotoxicity. CD4 cell count more than 250 cells per microliter was an independent predictor for hepatotoxicity both in men [relative risk = 1.22 (95% confidence interval: 1.04 to 1.44)] and in women [relative risk = 1.72 (95% confidence interval: 1.20 to 2.46)]. Severe hepatotoxicity was also more common among all persons with CD4 >250 cells per microliter. CONCLUSIONS:Hepatotoxicity was a common adverse effect of NVP among men and women with CD4 >250 cells per microliter. Chinese treatment guidelines should be considered to reflect this risk.