Orlando Immunology Center, 1707 North Mills Avenue, Orlando, FL, 32803, USA.
Department of Global Health, Emory University Rollins School of Public Health, 1518 Clifton Road NE, Atlanta, GA, 30322, USA.
AIDS Res Ther. 2021 May 3;18(1):26. doi: 10.1186/s12981-021-00352-0.
Dolutegravir (DTG) monotherapy results in virologic failure and the development of DTG resistance. Here, we evaluated virologic outcomes of patients switched to DTG functional mono- or dual therapy with a non-cytosine nucleoside analog (NA).
This retrospective, single center study included treatment-experienced patients switched to regimens containing ≥ 2 antiretrovirals between 8/13/13-11/22/14 who were later found to be on DTG functional mono- or dual therapy with a non-cytosine NA based on historical genotypes. Eligible patients were either suppressed or viremic at baseline and had ≥ 2 HIV-1 RNA measurements at least 4 weeks apart following switch. Demographics, laboratory values and clinical parameters were extracted from the charts of all eligible patients during study treatment until 12/31/2018 and were summarized using descriptive statistics. The primary endpoint was the proportion of patients with HIV-1 RNA < 50 copies/mL following switch.
Of 70 patients switched to DTG functional mono- or dual therapy, 39 were eligible; 19 (49%) were on DTG functional monotherapy and 20 (51%) were on DTG functional dual therapy with a non-cytosine NA. Historical genotypes indicated that all had an M184V/I, and 23 (59%) had an M184V/I and ≥ 1 additional NA mutation. The median duration of follow-up on study treatment was 50 weeks (range 12-244). Following switch, 32/39 (82%) patients achieved or maintained an HIV-1 RNA < 50 copies/mL and 7 (18%) had persistent HIV-1 RNA ≥ 50 copies/mL. Five viremic patients were found to be on functional dual therapy with DTG plus a non-cytosine NA and 2 were on DTG functional monotherapy. Five of these patients had post-switch genotypes ordered as a part of routine clinical care and there was no evidence of treatment-emergent resistance. Five were switched to a different DTG-containing regimen and achieved HIV-1 RNA < 50 copies/mL, 1 was switched to a non-DTG containing regimen and achieved HIV-1 RNA < 50 copies/mL and 1 was lost-to-follow up at week 36.
In this real-world cohort, the majority of whom had virus with the M184V/I and ≥ 1 additional NA mutation, switching to DTG functional mono-or dual therapy with a non-cytosine NA resulted in persistent HIV-1 RNA ≥ 50 copies/mL in 18%. None with post-switch genotypes developed treatment-emergent resistance.
多拉韦林（DTG）单药治疗会导致病毒学失败和 DTG 耐药性的发展。在此，我们评估了改用含非胞嘧啶核苷类似物（NA）的 DTG 功能性单药或双药治疗的患者的病毒学结果。
这是一项回顾性、单中心研究，纳入了 2013 年 8 月 13 日至 2014 年 11 月 22 日期间接受至少 2 种抗逆转录病毒药物治疗的经验丰富的患者，这些患者后来根据历史基因型发现使用了含≥2 种抗逆转录病毒药物的 DTG 功能性单药或双药治疗，其中包含一种非胞嘧啶 NA。符合条件的患者在基线时要么被抑制，要么病毒载量升高，并且在转换后至少有 4 周间隔的≥2 次 HIV-1 RNA 测量。在研究治疗期间，从所有符合条件的患者的图表中提取人口统计学、实验室值和临床参数，并使用描述性统计进行总结。主要终点是转换后 HIV-1 RNA<50 拷贝/mL 的患者比例。
在改用 DTG 功能性单药或双药治疗的 70 名患者中，有 39 名符合条件；其中 19 名（49%）使用 DTG 功能性单药治疗，20 名（51%）使用 DTG 功能性双药治疗，联合使用一种非胞嘧啶 NA。历史基因型表明，所有患者均携带 M184V/I，且 23 名（59%）患者携带 M184V/I 且至少有 1 种其他 NA 突变。研究治疗期间的中位随访时间为 50 周（范围 12-244）。转换后，39 名患者中有 32 名（82%）达到或维持 HIV-1 RNA<50 拷贝/mL，7 名（18%）HIV-1 RNA≥50 拷贝/mL。5 名病毒载量升高的患者发现正在接受含 DTG 和非胞嘧啶 NA 的功能性双药治疗，2 名患者正在接受 DTG 单药治疗。这 5 名患者的基因分型是作为常规临床护理的一部分订购的，没有发现治疗出现的耐药性证据。其中 5 名患者改用了不同的含 DTG 方案，HIV-1 RNA<50 拷贝/mL，1 名患者改用了不含 DTG 的方案，HIV-1 RNA<50 拷贝/mL，1 名患者在第 36 周失访。
在这个真实世界的队列中，大多数患者携带 M184V/I 和≥1 种其他 NA 突变，改用含非胞嘧啶 NA 的 DTG 功能性单药或双药治疗后，18%的患者 HIV-1 RNA≥50 拷贝/mL持续升高。没有发现携带新基因分型的患者出现治疗出现的耐药性。其中 5 名患者改用了含 DTG 的其他方案，HIV-1 RNA<50 拷贝/mL，1 名患者改用了不含 DTG 的方案，HIV-1 RNA<50 拷贝/mL，1 名患者在第 36 周失访。
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