title: Nevirapine plasma concentrations are associated with virologic response and hepatotoxicity in Chinese patients with HIV infection.
abstract: BACKGROUND
  Limited information is available on the relationship between nevirapine plasma concentrations and virologic response or liver toxicity in Chinese patients with HIV infection. The objective of this prospective study was to test this relationship and to determine the minimal therapeutic trough concentration of nevirapine for Chinese patients.
  
  
  METHODS
  A total of 227 HIV-infected, treatment naïve patients were enrolled into this study. Blood samples were taken at C(trough) (12 hr postdose) and C(2) (2 hr postdose) for measurement of nevirapine concentrations 6 months after treatment initiation. Therapeutic outcomes, viral load and CD4 cell count, were assessed at 3 and 6 months after starting therapy, while the evaluation of hepatotoxicity was undertaken 12 months after nevirapine treatment.
  
  
  RESULTS
  A significant correlation between nevirapine trough concentrations and viral load was noticed after 6 months of treatment, particularly in patients with partial response and viral failure (p<0.01). The therapeutic C(trough) of nevirapine for Chinese patients was determined to be 3.9 µg/ml using the receiver operating characteristic curve. Virologic failure was observed in 21% (6/29) of patients with low nevirapine concentrations (<3.9 µg/ml) versus 5% (4/87) in patients with concentrations higher than 3.9 µg/ml (p = 0.015). Hepatotoxicity was significantly associated with the median nevirapine trough concentrations among male patients (8.20 vs. 5.48 µg/ml, p = 0.015) and hepatitis C virus co-infection (p = 0.039).
  
  
  CONCLUSIONS
  Among Chinese patients with HIV infection, the therapeutic C(trough) of nevirapine was 3.9 µg/ml, higher than the recommended 3.0 µg/ml. The correlation between nevirapine concentrations, efficacy and hepatotoxicity suggests the benefit of dosage adjustment based on therapeutic drug monitoring among Chinese HIV-infected patients to optimize nevirapine containing antiretroviral therapy.
authors: Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors: Jia
authors: J
authors: Wang
authors: Huijuan
authors: H
authors: Kou
authors: Qiang
authors: Q
authors: Fu
authors: Yang
authors: Y
authors: Han
authors: Zhifeng
authors: Z
authors: Qiu
authors: Lingyan
authors: L
authors: Zuo
authors: Yanling
authors: Y
authors: Li
authors: Zhu
authors: Z
authors: Zhu
authors: Min
authors: M
authors: Ye
authors: Qing
authors: Q
authors: Ma
authors: Taisheng
authors: T
authors: Li
mesh_terms: D000328:Adult; D044466:Asian People; D018791:CD4 Lymphocyte Count; D002681:China; D002986:Clinical Trials as Topic; D003710:Demography; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000821:virology*; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000150:complications / Q000276:immunology / Q000821:virology; D006801:Humans; D016014:Linear Models; D008099:Liver / Q000473:pathology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D012367:RNA, Viral; D019829:Nevirapine