title: The interaction of CD4 T-cell count and nevirapine hepatotoxicity in China: a change in national treatment guidelines may be warranted.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Chengda
authors.initials: C
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Mengyu
authors.initials: M
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Qiu
authors.forename: Fuping
authors.initials: F
authors.lastname: Guo
authors.forename: Yanling
authors.initials: Y
authors.lastname: Li
authors.forename: Huanling
authors.initials: H
authors.lastname: Wang
authors.forename: Khalil G
authors.initials: KG
authors.lastname: Ghanem
authors.forename: Taisheng
authors.initials: T
authors.lastname: Li
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D018791:CD4 Lymphocyte Count; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology*; D002681:China; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage* / Q000009:adverse effects; D012044:Regression Analysis; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin