Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 413 90 Gothenburg, Sweden.
Department of Infectious Diseases, Hospital of Västmanland Västerås, 721 89 Västerås, Sweden.
Int J Antimicrob Agents. 2018 May;51(5):733-738. doi: 10.1016/j.ijantimicag.2018.01.009. Epub 2018 Jan 31.
Until the introduction of dolutegravir (DTG), people living with HIV (PLWH) who have developed nucleoside reverse transcriptase inhibitor (NRTI) mutations have had few other treatment options outside of regimens based on ritonavir-boosted protease inhibitors (PI/r). Here we report treatment results among PLWH in Sweden with pre-existing NRTI mutations on antiretroviral treatment (ART) with DTG and one to two NRTIs. All PLWH on ART with DTG and one to two NRTIs with pre-existing NRTI mutations were retrospectively identified from the National InfCare HIV database. As controls, PLWH on PI/r and one to two NRTIs, matched according to Genotypic Susceptibility Score and observation time, were included. Data were collected as long as the study population was on treatment with DTG; controls were monitored for the same interval. Outcome was classified as either treatment success or failure. In total, 244 participants (122 individuals treated with DTG and 122 individuals treated with PI/r) were included. Median observation time was 78 weeks (interquartile range 50-98 weeks) for participants on DTG and 75 weeks (50-101 weeks) for individuals on PI/r. Viral failure was detected in four individuals treated with DTG and three individuals treated with PI/r, resulting in similar success rates of 96.7% and 97.5%, respectively. No new mutations were found among participants with treatment failure. DTG in combination with one to two NRTIs was as efficient as PI/r in individuals with pre-existing NRTI mutations in this setting. It may be considered an alternative to PI/r-based ART even in the presence of NRTI resistance.
在多拉韦林（DTG）问世之前，患有核苷逆转录酶抑制剂（NRTI）耐药突变的 HIV 感染者（PLWH）除了基于利托那韦增效蛋白酶抑制剂（PI/r）的方案之外，几乎没有其他治疗选择。在这里，我们报告了在瑞典，使用 DTG 和一种或两种 NRTI 治疗有预先存在的 NRTI 耐药突变的 PLWH 的治疗结果。所有在 DTG 联合一种或两种 NRTI 治疗的 PLWH 中，都根据基因型耐药评分和观察时间，从国家 InfCare HIV 数据库中回顾性地识别出预先存在的 NRTI 耐药突变。作为对照，我们纳入了在 PI/r 和一种或两种 NRTI 治疗中，与耐药评分和观察时间相匹配的 PLWH。只要研究人群正在接受 DTG 治疗，就会收集数据；对照组监测相同的时间间隔。结果分为治疗成功或失败。总共纳入了 244 名参与者（122 名接受 DTG 治疗的个体和 122 名接受 PI/r 治疗的个体）。DTG 组的中位观察时间为 78 周（50-98 周），PI/r 组为 75 周（50-101 周）。在接受 DTG 治疗的 4 名个体和接受 PI/r 治疗的 3 名个体中发现了病毒失败，导致治疗成功率分别为 96.7%和 97.5%，结果相似。在治疗失败的参与者中没有发现新的突变。在这种情况下，DTG 联合一种或两种 NRTI 与 PI/r 一样有效，即使存在 NRTI 耐药。它可能被认为是 PI/r 为基础的 ART 的替代方案，甚至在存在 NRTI 耐药的情况下。
