Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Bangkok 10400, Thailand.
J Clin Virol. 2010 Apr;47(4):330-4. doi: 10.1016/j.jcv.2010.01.018. Epub 2010 Feb 25.
Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens have been extensively used for treatment of HIV infection in resource-limited settings. Treatment options after failing an initial regimen are limited because of cross-resistance of NNRTIs.
To determine the factors associated with reduced response to etravirine among patients with virological failure.
A retrospective study was conducted. We stratified patients into two groups by the total weighted scores of etravirine-resistance-associated mutations (ETV-RAMs), highest response (score 0-2, N=123) and intermediate and reduced response (score > or =2.5, N=61). Factors associated with a score of > or =2.5 were evaluated.
There were 184 patients with mean (SD) age of 42 (9) years old and 60% were males. Of all, 68% used NNRTI in the failing regimen and 51% used stavudine/lamivudine as a backbone. Common ETV-RAMs included Y181C (27%), G190A (17%), and K101E (10%). Higher proportion of K101E, K101P, Y181C, G190S, and M230L were found in patients with a score of > or =2.5 (p<0.05, all). By univariate logistic regression, using protease inhibitor (OR 0.22, 95% CI 0.07-0.67), nevirapine (OR 10.56, 95% CI 4.04-27.74), and efavirenz (OR 2.91, 95% CI 1.01-2.51) in the current regimen were associated with a score of > or =2.5. By multiple logistic regression, only using nevirapine was associated with a score of > or =2.5 (OR 7.61, 95% CI 2.40-24.06).
Using nevirapine in the failing regimen was associated with intermediate and reduced response to ETV. The recommendation of using nevirapine as a preferred NNRTI should be re-considered in resource-limited settings where efavirenz is accessible.
非核苷类逆转录酶抑制剂(NNRTI)为基础的方案已被广泛用于资源有限的环境中治疗 HIV 感染。由于 NNRTIs 的交叉耐药性,初始方案失败后的治疗选择有限。
确定与治疗失败患者对依曲韦林反应降低相关的因素。
进行了一项回顾性研究。我们根据依曲韦林耐药相关突变(ETV-RAMs)的总加权评分将患者分为两组,最高反应(评分 0-2,N=123)和中间及降低反应(评分>或=2.5,N=61)。评估了与评分>或=2.5 相关的因素。
共有 184 名患者,平均(SD)年龄为 42(9)岁,60%为男性。其中,68%的患者在失败的方案中使用了 NNRTI,51%的患者使用司他夫定/拉米夫定作为骨干。常见的 ETV-RAMs 包括 Y181C(27%)、G190A(17%)和 K101E(10%)。评分>或=2.5 的患者中,K101E、K101P、Y181C、G190S 和 M230L 的比例更高(p<0.05,均)。单变量 logistic 回归显示,当前方案中使用蛋白酶抑制剂(OR 0.22,95%CI 0.07-0.67)、奈韦拉平(OR 10.56,95%CI 4.04-27.74)和依非韦伦(OR 2.91,95%CI 1.01-2.51)与评分>或=2.5 相关。多变量 logistic 回归显示,只有使用奈韦拉平与评分>或=2.5 相关(OR 7.61,95%CI 2.40-24.06)。
在失败的方案中使用奈韦拉平与依曲韦林的中间和降低反应相关。在获得依非韦伦的资源有限环境中,应重新考虑将奈韦拉平作为首选 NNRTI 的建议。