Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, University of Zürich, Zürich, Switzerland.
J Acquir Immune Defic Syndr. 2011 May 1;57(1):24-31. doi: 10.1097/QAI.0b013e318211925e.
Nucleoside reverse transcriptase inhibitors (NRTIs) are often administered in salvage therapy even if genotypic resistance tests (GRTs) indicate high-level resistance, but little is known about the benefit of these additional NRTIs.
The effect of <2 compared with 2 NRTIs on viral suppression (HIV-1 RNA < 50 copies/mL) at week 24 was studied in salvage patients receiving raltegravir. Intent-to-treat and per-protocol analyses were performed; last observation carried forward imputation was used to deal with missing information. Logistic regressions were weighted to create a pseudopopulation in which the probability of receiving <2 and 2 NRTIs was unrelated to baseline factors predicting treatment response.
One-hundred thirty patients were included, of whom 58.5% (n = 76) received <2 NRTIs. NRTIs were often replaced by other drug classes. Patients with 2 NRTIs received less additional drug classes compared with patients with <2 NRTIs [median (IQR): 1 (1-2) compared with 2 (1-2), P Wilcoxon < 0.001]. The activity of non-NRTI treatment components was lower in the 2 NRTIs group compared with the <2 NRTIs group [median (IQR) genotypic sensitivity score: 2 (1.5-2.5) compared with 2.5 (2-3), P Wilcoxon < 0.001]. The administration of <2 NRTIs was associated with a worse viral suppression rate at week 24. The odds ratios were 0.34 (95% confidence interval: 0.13 to 0.89, P = 0.027) and 0.19 (95% confidence interval: 0.05 to 0.79, P = 0.023) when performing the last observation carried forward and the per-protocol approach, respectively.
Our findings showed that partially active or inactive NRTIs contribute to treatment response, and thus the use of 2 NRTIs in salvage regimens that include raltegravir seems warranted.
核苷逆转录酶抑制剂(NRTIs)经常在挽救治疗中使用,即使基因耐药测试(GRTs)显示高水平耐药,但对于这些额外 NRTIs 的益处知之甚少。
在接受拉替拉韦的挽救性患者中,研究了与 24 周时病毒抑制(HIV-1 RNA < 50 拷贝/mL)相比,<2 种 NRTI 与 2 种 NRTI 的效果。进行意向治疗和方案分析;使用最后观察结转插补处理缺失信息。使用逻辑回归对数据进行加权处理,以创建一个伪人群,其中接受 <2 种和 2 种 NRTI 的概率与预测治疗反应的基线因素无关。
共纳入 130 例患者,其中 58.5%(n = 76)接受 <2 种 NRTI。NRTIs 经常被其他药物类别取代。与接受 <2 种 NRTI 的患者相比,接受 2 种 NRTI 的患者接受的其他药物类别较少[中位数(IQR):1(1-2)与 2(1-2),P Wilcoxon < 0.001]。与 <2 种 NRTI 组相比,2 种 NRTI 组中非 NRTI 治疗成分的活性较低[中位数(IQR)基因型敏感性评分:2(1.5-2.5)与 2.5(2-3),P Wilcoxon < 0.001]。接受 <2 种 NRTI 与 24 周时病毒抑制率较差相关。当进行最后观察结转和方案分析时,比值比分别为 0.34(95%置信区间:0.13 至 0.89,P = 0.027)和 0.19(95%置信区间:0.05 至 0.79,P = 0.023)。
我们的研究结果表明,部分活性或非活性 NRTI 有助于治疗反应,因此在包括拉替拉韦的挽救方案中使用 2 种 NRTI 似乎是合理的。