Li Wen-juan, Dai Yi, Han Yang, Qiu Zhi-feng, Xie Jing, Zuo Ling-yan, Li Yan-ling, Li Tai-sheng
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.
Zhonghua Yi Xue Za Zhi. 2011 May 24;91(19):1318-22.
To evaluate the safety profiles of three nevirapine-based therapies for antiretroviral-naive Chinese adults infected with HIV-1 (human immunodeficiency virus-1).
For this prospective multicentric randomized trial, a total of 198 antiretroviral-naive HIV-1 positive patients were recruited from 13 research centers in China. They were randomly assigned to receive three NVP-based antiretroviral therapies for 52 weeks: Group A, AZT (zidovudine) + DDI (didanosine) + NVP (nevirapine); Group B, D4T (stavudine) + 3TC (lamivudine) + NVP; Group C, AZT + 3TC + NVP. Their clinical events and laboratory examinations were monitored at baseline and the end of weeks 4, 8, 12, 24, 36 & 52 post-HAART (highly active antiretroviral therapy) to evaluate the occurrence of adverse events (AEs). The chi-square or Fisher's exact test was employed to compare the rates of AEs among three treatment groups. Multivariate logistic regression analyses were used to identify the factors associated with hepatotoxicity. For all tests, P < 0.05 was considered as statistically significant.
During the 52-week HAART, 968 cases of AEs occurred in 188 patients (95.0%). Only 37.4% experienced grade 3/4 AE. And 37 patients withdrew because of HAART-related AEs (18.7%). The common AEs were hepatotoxicity, bone morrow suppression, gastrointestinal disorders, rash and hyperlipidemia, etc. Most instances of AEs occurred during the early 12 weeks. The total count of AEs for each group had no statistic significant difference (P = 0.403). Bone marrow suppression was more strongly associated with an AZT-containing HAART and it was especially prone to gastrointestinal disorders when combined with DDI. The introduction of D4T or DDI led more frequently to peripheral neuropathy and hyperlipidemia. Logistic regression analysis indicated that presence of hepatotoxicity was associated with a higher baseline level of CD4 (CD4 count > 250/µl) (OR = 2.08, 95%CI: 1.114 - 3.882, P = 0.021).
The common reasons of discontinuing HAART are hepatotoxicity, gastrointestinal disorders, bone marrow suppression and rash. The occurrence of AEs should be vigorously monitored especially during the early 3 months of HAART. The HIV/AIDS patients with a CD4 count of > 250/µl shall avoid any NVP-containing regimen.
评估三种以奈韦拉平为基础的疗法用于初治的感染人类免疫缺陷病毒1型（HIV-1）的中国成年患者的安全性。
在这项前瞻性多中心随机试验中，从中国13个研究中心招募了总共198例初治的HIV-1阳性患者。他们被随机分配接受三种基于奈韦拉平的抗逆转录病毒疗法，为期52周：A组，齐多夫定（AZT）+去羟肌苷（DDI）+奈韦拉平（NVP）；B组，司他夫定（D4T）+拉米夫定（3TC）+奈韦拉平；C组，AZT + 3TC + NVP。在基线以及高效抗逆转录病毒治疗（HAART）后第4、8、12、24、36和52周结束时监测他们的临床事件和实验室检查，以评估不良事件（AE）的发生情况。采用卡方检验或Fisher精确检验比较三个治疗组之间的AE发生率。多变量逻辑回归分析用于确定与肝毒性相关的因素。对于所有检验，P < 0.05被认为具有统计学意义。
在52周的HAART期间，188例患者（95.0%）发生了968例AE。只有37.4%的患者经历了3/4级AE。37例患者因与HAART相关的AE而退出（18.7%）。常见的AE包括肝毒性、骨髓抑制、胃肠道疾病、皮疹和高脂血症等。大多数AE发生在最初的12周内。每组AE的总数无统计学显著差异（P = 0.403）。骨髓抑制与含AZT的HAART更密切相关，并且与DDI联合使用时尤其容易发生胃肠道疾病。引入D4T或DDI更频繁地导致周围神经病变和高脂血症。逻辑回归分析表明肝毒性的存在与较高的基线CD4水平（CD4计数> 250/µl）相关（OR = 2.08，95%CI：1.114 - 3.882，P = 0.021）。
停止HAART的常见原因是肝毒性、胃肠道疾病、骨髓抑制和皮疹。应大力监测AE的发生，尤其是在HAART的前3个月。CD4计数> 250/µl的HIV/AIDS患者应避免任何含NVP的治疗方案。
