Nevirapine Plasma Concentrations Are Associated with Virologic Response and Hepatotoxicity in Chinese Patients with HIV Infection

作者：Jia Wang, Huijuan Kou, Qiang Fu, Yang Han, Zhifeng Qiu, Lingyan Zuo, Yanling Li, Zhu Zhu, Min Ye, Qing Ma, Taisheng Li · 发表于：PLoS ONE · 年份：2011 · DOI：10.1371/journal.pone.0026739 · 被引用次数：37 · 研究领域：HIV/AIDS drug development and treatment、HIV-related health complications and treatments、HIV Research and Treatment

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...