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在有或无既往M184V突变的HIV-1感染得到抑制患者的回顾性观察队列中,转换为多替拉韦(DTG)加拉米夫定(3TC)的病毒学疗效:LAMRES研究

Virological efficacy of switch to DTG plus 3TC in a retrospective observational cohort of suppressed HIV-1 patients with or without past M184V: the LAMRES study.

作者信息

Santoro Maria Mercedes, Armenia Daniele, Teyssou Elisa, Santos José Ramón, Charpentier Charlotte, Lambert-Niclot Sidonie, Antinori Andrea, Katlama Christine, Descamps Diane, Perno Carlo Federico, Calvez Vincent, Paredes Roger, Ceccherini-Silberstein Francesca, Marcelin Anne Geneviève

机构信息

Department of Experimental Medicine, University of Rome 'Tor Vergata', Rome, Italy.

Saint Camillus International University of Health Sciences, Rome, Italy.

出版信息

J Glob Antimicrob Resist. 2022 Dec;31:52-62. doi: 10.1016/j.jgar.2022.07.022. Epub 2022 Aug 7.

Abstract

OBJECTIVES

The aim of this study was to assess the efficacy of dolutegravir plus lamivudine (DTG+3TC) in a large set of virologically suppressed HIV-1 infected individuals with or without past M184V mutation.

METHODS

This observational study included individuals who switched to DTG+3TC with ≥1 genotype before switch. Survival analysis was used to evaluate the role of past M184V on virological rebound (VR) or blips after DTG+3TC switch.

RESULTS

A total of 712 individuals followed in several clinical centres in France, Italy and Spain were analysed. Past M184V was present in 60 (8.4%) individuals. By 3 years after switch, the overall probability of VR and blips was 6.7% and 6.9%, respectively, without any statistical significance according to the presence/absence of past M184V. A significantly higher probability of VR was found in individuals harbouring M184V before DTG+3TC with a duration of virological suppression (Ts) ≤.3.5 years compared to others (M184V+Ts ≤.3.5 years: 22.7%; M184M+Ts ≤.3.5 years: 9.0%; M184V+Ts >3.5 years: 7.8%; M184M+Ts >3.5 years: 4.9%; P = 0.007). This finding was not confirmed in multivariable models adjusting for behavioural and demographic variables. Genotypic resistance test after VR under DTG+3TC was available for 8/39 individuals; one poorly adherent individual developed M184V. No resistance to INIs was found.

CONCLUSION

In this retrospective observational study, the probability of VR and blips in patients switching to DTG+3TC was very low after 3 years of treatment regardless M184V. The effect of a short duration of previous virological suppression in individuals with M184V remains troubling and needs ad hoc clinical trials to be confirmed.

摘要

目的

本研究旨在评估多替拉韦加拉米夫定(DTG+3TC)在大量病毒学抑制的HIV-1感染者中的疗效,这些感染者既往有或无M184V突变。

方法

这项观察性研究纳入了在转换治疗前至少有1种基因型的、转换为DTG+3TC的个体。生存分析用于评估既往M184V对转换为DTG+3TC后病毒学反弹(VR)或病毒学波动的作用。

结果

对法国、意大利和西班牙多个临床中心随访的712名个体进行了分析。60名(8.4%)个体存在既往M184V。转换治疗3年后,VR和病毒学波动的总体概率分别为6.7%和6.9%,根据既往M184V的有无,无任何统计学意义。与其他个体相比,在DTG+3TC治疗前携带M184V且病毒学抑制持续时间(Ts)≤3.5年的个体中,VR的概率显著更高(M184V+Ts≤3.5年:22.7%;M184M+Ts≤3.5年:9.0%;M184V+Ts>3.5年:7.8%;M184M+Ts>3.5年:4.9%;P=0.007)。在对行为和人口统计学变量进行调整的多变量模型中,这一发现未得到证实。在DTG+3TC治疗下VR后,8/39名个体可进行基因型耐药检测;1名依从性差的个体出现了M184V。未发现对整合酶抑制剂(INI)的耐药性。

结论

在这项回顾性观察性研究中,转换为DTG+3TC的患者在治疗3年后,无论有无M184V,VR和病毒学波动的概率都非常低。既往病毒学抑制持续时间短对M184V个体的影响仍然令人担忧,需要专门的临床试验来证实。

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