Chen Guan-Jhou, Lee Yu-Lin, Lee Chen-Hsiang, Sun Hsin-Yun, Cheng Chien-Yu, Tsai Hung-Chin, Huang Sung-Hsi, Lee Yi-Chieh, Hsieh Min-Han, Chang Sui-Yuan, Chuang Yu-Chung, Su Li-Shin, Chang Sui-Fang, Tang Hung-Jen, Hung Chien-Ching
Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin County, Taiwan.
Department of Internal Medicine, Changhua Christian Hospital, Changhua County, Taiwan.
J Antimicrob Chemother. 2020 Oct 1;75(10):2986-2993. doi: 10.1093/jac/dkaa287.
Real-world experience regarding the effectiveness of co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (EVG/C/FTC/TAF) as a switch regimen is sparse among people living with HIV (PLWH) harbouring the M184V/I mutation with or without thymidine analogue-associated mutations (TAMs).
In this retrospective multicentre study, PLWH who were switched to EVG/C/FTC/TAF after having achieved viral suppression (plasma HIV RNA <200 copies/mL) for 6 months or longer were included. Patients with archived M184V/I mutation (case patients) were matched to controls without M184V/I mutation at a 1:4 ratio. Patients with a history of virological failure or resistance to elvitegravir were excluded. The primary endpoint was virological non-success (plasma HIV RNA ≥50 copies/mL) at Week 48 of switch using a modified FDA snapshot analysis.
Overall, 100 case patients with the M184V/I mutation were identified, including 6 (6.0%) with K65R and 13 (13.0%) with at least one TAM, and were matched to 400 controls in terms of gender, age (mean = 40.3 versus 39.7 years) and cumulative exposure duration to tenofovir disoproxil fumarate (median = 146 versus 143 weeks). At Week 48, the rate of virological non-success for the case patients and controls was 5.0% (5/100) and 3.3% (13/400), respectively (difference = 1.7%; 95% CI = -2.9%-6.3%), while the rate of virological success was 88.0% and 89.5% for the case patients and controls, respectively. The presence of the K65R mutation or TAMs was not associated with virological non-response.
Among virally suppressed PLWH, EVG/C/FTC/TAF is effective in maintaining viral suppression at Week 48 despite archived M184V/I mutation with or without TAMs.
对于携带M184V/I突变且有或无胸苷类似物相关突变（TAMs）的HIV感染者（PLWH），作为转换方案的复方elvitegravir、cobicistat、恩曲他滨和替诺福韦艾拉酚胺（EVG/C/FTC/TAF）有效性的真实世界经验较少。
在这项回顾性多中心研究中，纳入了在实现病毒抑制（血浆HIV RNA<200拷贝/mL）6个月或更长时间后转换为EVG/C/FTC/TAF的PLWH。将存档有M184V/I突变的患者（病例患者）与无M184V/I突变的对照按1:4的比例进行匹配。排除有病毒学失败史或对elvitegravir耐药的患者。主要终点是使用改良的FDA快照分析在转换后第48周时病毒学未成功（血浆HIV RNA≥50拷贝/mL）。
总体而言，共识别出100例有M184V/I突变的病例患者，其中6例（6.0%）有K65R突变，13例（13.0%）有至少一种TAM，并在性别、年龄（平均分别为40.3岁和39.7岁）以及富马酸替诺福韦二吡呋酯的累积暴露持续时间（中位数分别为146周和143周）方面与400例对照进行了匹配。在第48周时，病例患者和对照的病毒学未成功发生率分别为5.0%（5/100）和3.3%（13/400）（差异=1.7%；95%CI=-2.9%-6.3%），而病例患者和对照的病毒学成功发生率分别为88.0%和89.5%。K65R突变或TAMs的存在与病毒学无应答无关。
在病毒得到抑制的PLWH中，尽管存在存档的有或无TAMs的M184V/I突变，EVG/C/FTC/TAF在第48周时仍能有效维持病毒抑制。
