Annan Naa Torshie, Nelson Mark, Mandalia Sundhiya, Bower Mark, Gazzard Brian G, Stebbing Justin
Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom.
J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):140-6. doi: 10.1097/QAI.0b013e3181a56e81.
We wished to determine the efficacy of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in antiretroviral-naive patients commencing highly active antiretroviral therapy (HAART) and to evaluate the effect of calendar year, nucleoside analogue reverse transcriptase inhibitor (NRTI) backbone, sex, and ethnicity on treatment outcome.
Antiretroviral-naive individuals commencing efavirenz or nevirapine with dual-nucleoside analogue backbones were identified from a prospective database. Virological success was defined as HIV viral load <500 copies per milliliter. Treatment failure was defined as a switch or discontinuation of NNRTI or documented virological failure (2 measurements with viral load >500 copies/mL).
From a cohort of 994 individuals, 73% commenced efavirenz- and 27% nevirapine-containing regimens. We found no differences between the 2 treatment groups for the time to virological success (proportion with virological success: efavirenz 71%, nevirapine 72%, P = 0.77) or treatment failure (proportion failing treatment: efavirenz 23%, nevirapine 26%, P = 0.58). There was a significant difference in the calendar year for commencing HAART for the time to virological success and treatment failure (P < 0.001). In the multivariable model, the likelihood of virological success for stavudine/lamivudine was 52% [relative hazard (RH) 1.52, 95% confidence interval (CI) 1.17 to 1.97, P = 0.002]. The nonthymidine analogue backbones as a group seemed to be least likely associated with virological success (RH 0.62, 95% CI 0.48 to 0.80, P < 0.001). This was however largely driven by tenofovir/didanosine being significantly associated with treatment failure (RH 6.48, 95% CI 3.81 to 11.0, P < 0.001). Sex and ethnicity were not associated with treatment outcome.
We found no significant differences between nevirapine and efavirenz for the time to virological success or treatment failure. Calendar year of commencing HAART and NRTI backbones were significant predictors of virological success and treatment failure, explaining differences in data to the 2NN study. The weaker the NNRTI (or the weaker the protease inhibitor) the more important the NRTI backbone becomes.
我们希望确定在初治抗逆转录病毒治疗（HAART）患者中，基于非核苷类逆转录酶抑制剂（NNRTI）的治疗方案的疗效，并评估历年、核苷类逆转录酶抑制剂（NRTI）主干药物、性别和种族对治疗结果的影响。
从一个前瞻性数据库中识别出开始使用依非韦伦或奈韦拉平联合双核苷类主干药物的初治抗逆转录病毒治疗个体。病毒学成功定义为HIV病毒载量<500拷贝/毫升。治疗失败定义为更换或停用NNRTI或记录的病毒学失败（两次测量病毒载量>500拷贝/毫升）。
在994名个体的队列中，73%开始使用含依非韦伦的方案，27%开始使用含奈韦拉平的方案。我们发现两个治疗组在病毒学成功时间（病毒学成功比例：依非韦伦71%，奈韦拉平72%，P = 0.77）或治疗失败（治疗失败比例：依非韦伦23%，奈韦拉平26%，P = 0.58）方面没有差异。开始HAART的历年在病毒学成功时间和治疗失败方面存在显著差异（P < 0.001）。在多变量模型中，司他夫定/拉米夫定的病毒学成功可能性为52%[相对风险（RH）1.52，95%置信区间（CI）1.17至1.97，P = 0.002]。非胸苷类似物主干药物作为一个组似乎与病毒学成功关联最小（RH 0.62，95%CI 0.48至0.80，P < 0.001）。然而，这在很大程度上是由替诺福韦/去羟肌苷与治疗失败显著相关所驱动的（RH 6.48，95%CI 3.81至11.0，P < 0.001）。性别和种族与治疗结果无关。
我们发现奈韦拉平和依非韦伦在病毒学成功时间或治疗失败方面没有显著差异。开始HAART的历年和NRTI主干药物是病毒学成功和治疗失败的重要预测因素，解释了与2NN研究数据的差异。NNRTI越弱（或蛋白酶抑制剂越弱），NRTI主干药物就越重要。
