Li Taisheng, Dai Yi, Kuang Jiqiu, Jiang Jingmei, Han Yang, Qiu Zhifeng, Xie Jing, Zuo Lingyan, Li Yanling
Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
PLoS One. 2008;3(12):e3918. doi: 10.1371/journal.pone.0003918. Epub 2008 Dec 12.
The purpose of this study was to evaluate the efficacy and safety of three nevirapine-based antiretroviral treatments for adult antiretroviral-naïve Chinese patients with HIV-1 infection.
This was a prospective, multicenter study. 198 antiretroviral-naïve HIV-1 positive subjects with CD4 lymphocyte counts between 100/ul and 350/ul and plasma HIV-1 RNA levels more than 500 copies/ml were randomized to start three NVP-based antiretroviral treatments: group A, NVP+AZT+ddI; group B, NVP+3TC+d4T; group C, NVP+AZT+3TC. Viral responses, immunologic responses, adverse events and drug resistance were monitored at baseline and the end of week 4, 12, 24, 36, 52. Viralogical response and immunological response were also compared in different strata of baseline CD4 T lymphocyte counts and plasma HIV-1 RNA concentrations. At baseline, the plasma HIV-1 RNA was 4.44+/-0.68, 4.52+/-0.71 and 4.41+/-0.63 lg copies/ml in group A, B and C respectively (p = 0.628). At the end of the study, the plasma viral load reached 2.54+/-1.11, 1.89+/-0.46 and 1.92+/-0.58 lg copies/ml in group A, B and C respectively (p<0.001). At week 52, suppression of plasma HIV-1 RNA to less than 50 copies/ml was achieved in more patients in group B and C than in group A (68.2%, 69% vs. 39.7%; p<0.001). In planned subgroup analyses, the decrease of viral response rate was seen in group A when CD4 cell count >200/ul (subgroup H). But in subgroup L, viral response rate of three groups has no significant statistic difference. There were no statistically significant differences among three groups in immunological response within any of the CD4 or pVL strata. 3 out of 193 patients with available genotype at baseline showed primary drug resistant. Of 26 patients with virologic failure, 17 patients showed secondary drug resistant, 16 subjects in group A and 1 subject in group B. Logistic regression analysis indicated that presence of hepatotoxicity was associated with HCV-Ab positive (OR = 2.096, 95%CI: 1.106-3.973, P = 0.023) and higher CD4 baseline (CD4 count >250/ul) (OR = 2.096, 95%CI: 1.07-4.107, P = 0.031).
Our findings strongly support the use of 3TC+d4T and 3TC+AZT as the nucleoside analogue combination in NVP-based antiretroviral therapy. The regimen of AZT+ddI+NVP produced poor virological response especially in the stratum of CD4 count more than 200/ul. More patients showed secondary drug resistant in this arm too. Patients with HCV-Ab+ and CD4 count >250/ul appear to have significantly high risk of hepatoxicity.
ClinicalTrials.gov NCT00618176.
本研究旨在评估三种以奈韦拉平为基础的抗逆转录病毒疗法对未接受过抗逆转录病毒治疗的成年中国HIV-1感染患者的疗效和安全性。
这是一项前瞻性、多中心研究。198例未接受过抗逆转录病毒治疗、CD4淋巴细胞计数在100/ul至350/ul之间且血浆HIV-1 RNA水平超过500拷贝/ml的HIV-1阳性受试者被随机分组，开始三种基于奈韦拉平的抗逆转录病毒治疗：A组，奈韦拉平+齐多夫定+去羟肌苷；B组，奈韦拉平+拉米夫定+司他夫定；C组，奈韦拉平+齐多夫定+拉米夫定。在基线以及第4、12、24、36、52周结束时监测病毒反应、免疫反应、不良事件和耐药情况。还对不同基线CD4 T淋巴细胞计数和血浆HIV-1 RNA浓度分层中的病毒学反应和免疫反应进行了比较。基线时，A组、B组和C组的血浆HIV-1 RNA分别为4.44±0.68、4.52±0.71和4.41±0.63 lg拷贝/ml（p = 0.628）。研究结束时，A组、B组和C组的血浆病毒载量分别达到2.54±1.11、1.89±0.46和1.92±0.58 lg拷贝/ml（p<0.001）。在第52周时，B组和C组中血浆HIV-1 RNA抑制至低于50拷贝/ml的患者比A组更多（68.2%、69%对39.7%；p<0.001）。在计划的亚组分析中，当CD4细胞计数>200/ul时（亚组H），A组的病毒反应率下降。但在亚组L中，三组的病毒反应率无统计学显著差异。在任何CD4或pVL分层的免疫反应方面，三组之间无统计学显著差异。193例基线时有可用基因型的患者中有3例显示出原发性耐药。在26例病毒学失败的患者中，17例显示出继发性耐药，A组16例，B组1例。逻辑回归分析表明，肝毒性的存在与HCV-Ab阳性（OR = 2.096，95%CI：1.106 - 3.973，P = 0.023）以及较高的基线CD4（CD4计数>250/ul）（OR = 2.096，95%CI：1.07 - 4.
