拉米夫定联合多替拉韦作为一种转换策略在多中心 HIV-1 感染、病毒学抑制患者队列中的长期疗效和耐受性数据。
Long-term data on the efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multi-centre cohort of HIV-1-infected, virologically suppressed patients.
机构信息
Institute of Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy; Mater Olbia Hospital, Olbia, Italy.
Institute of Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy.
出版信息
Int J Antimicrob Agents. 2019 Dec;54(6):728-734. doi: 10.1016/j.ijantimicag.2019.09.002. Epub 2019 Sep 12.
BACKGROUND
Results from clinical trials and observational studies suggest that lamivudine plus dolutegravir (3TC+DTG) could be an effective and tolerated option for simplification in human immunodeficiency virus (HIV)-1-positive patients.
MATERIALS AND METHODS
This observational study enrolled HIV-1-infected, virologically suppressed patients switching to 3TC+DTG. Kaplan-Meyer survival analysis was performed to evaluate time to virological failure (VF; defined by a single HIV-RNA determination ≥1000 copies/mL or by two consecutive HIV-RNA determinations ≥50 copies/mL) and time to treatment discontinuation (TD; defined as interruption of either 3TC or DTG), Cox regression was performed to assess predictors, and linear mixed model was performed for repeated measures to measure changes in immunological and metabolic parameters.
RESULTS
Five hundred and fifty-six patients were eligible for analysis. Their median CD4+ count at baseline was 668 cells/mm and median time of virological suppression was 88 months. Estimated probabilities of maintaining virological suppression at 96 and 144 weeks of follow-up were 97.5% [standard deviation (SD) 0.8] and 96.5% (SD 1.0), respectively. Years since HIV diagnosis was the only predictor of VF. In patients with time of virological suppression <88 months, the rate of VF was higher in the presence of the M184V mutation. Estimated probabilities of remaining on 3TC+DTG at 96 and 144 weeks of follow-up were 79.2% (SD 1.9) and 75.2% (SD 2.2), respectively. A significant increase in CD4 cell count (+44 cells/mm, P=0.015), CD4/CD8 ratio (+0.10, P=0.002) and high-density lipoprotein cholesterol (+5.4 mg/dL, P=0.036) was found at 144 weeks of follow-up; meanwhile, total cholesterol (-9.1 mg/dL, P=0.007) and triglycerides (-2.7, P=0.009) decreased significantly.
CONCLUSIONS
These findings confirm the efficacy and tolerability of 3TC+DTG in virologically suppressed patients.
背景
临床试验和观察性研究的结果表明，拉米夫定联合多替拉韦（3TC+DTG）可能是一种有效且耐受的选择，可用于简化 HIV-1 阳性患者的治疗。
材料和方法
这项观察性研究纳入了接受拉米夫定转换为 3TC+DTG 治疗的 HIV-1 感染、病毒学抑制的患者。采用 Kaplan-Meier 生存分析评估病毒学失败（VF；定义为单次 HIV-RNA 测定值≥1000 拷贝/mL 或两次连续 HIV-RNA 测定值≥50 拷贝/mL）和治疗停药（TD；定义为中断拉米夫定或多替拉韦的治疗）的时间。采用 Cox 回归评估预测因素，并采用线性混合模型进行重复测量，以评估免疫和代谢参数的变化。
结果
556 例患者符合分析条件。他们的基线 CD4+计数中位数为 668 个细胞/mm，病毒学抑制中位时间为 88 个月。随访 96 和 144 周时维持病毒学抑制的估计概率分别为 97.5%（标准差 [SD] 0.8）和 96.5%（SD 1.0）。HIV 诊断后的时间是 VF 的唯一预测因素。在病毒学抑制时间<88 个月的患者中，M184V 突变的存在与 VF 发生率较高相关。随访 96 和 144 周时继续使用 3TC+DTG 的估计概率分别为 79.2%（SD 1.9）和 75.2%（SD 2.2）。随访 144 周时，CD4 细胞计数（增加 44 个细胞/mm，P=0.015）、CD4/CD8 比值（增加 0.10，P=0.002）和高密度脂蛋白胆固醇（增加 5.4 mg/dL，P=0.036）显著增加；同时，总胆固醇（降低 9.1 mg/dL，P=0.007）和甘油三酯（降低 2.7，P=0.009）显著降低。
结论
这些发现证实了拉米夫定联合多替拉韦在病毒学抑制患者中的疗效和耐受性。
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