携带 HIV-1 E157Q 整合酶突变的患者中不同一线 ART 方案的病毒学结局：一项多中心回顾性研究。

Virological outcomes of various first-line ART regimens in patients harbouring HIV-1 E157Q integrase polymorphism: a multicentre retrospective study.

机构信息

Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.

AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.

出版信息

J Antimicrob Chemother. 2023 Dec 1;78(12):2859-2868. doi: 10.1093/jac/dkad319.

DOI:10.1093/jac/dkad319

PMID:37856677

Abstract

BACKGROUND

Integrase strand transfer inhibitors (INSTIs) are recommended as first-line ART for people living with HIV (PLWH) in most guidelines. The INSTI-resistance-associated mutation E157Q, a highly prevalent (2%-5%) polymorphism of the HIV-1 (human immunodeficiency virus type 1) integrase gene, has limited data on optimal first-line ART regimens. We assessed the virological outcomes of various first-line ART regimens in PLWH with E157Q in real-world settings.

METHODS

A multicentre retrospective observational study was conducted on PLWH who underwent integrase genotypic drug-resistance testing before ART initiation between 2008 and 2019 and were found to have E157Q. Viral suppression (<50 copies/mL) rate at 24 and 48 weeks, time to viral suppression and time to viral rebound (≥100 copies/mL) were compared among the first-line ART regimens.

RESULTS

E157Q was detected in 167 (4.1%) of 4043 ART-naïve PLWH. Among them, 144 had available clinical data after ART initiation with a median follow-up of 1888 days. Forty-five started protease inhibitors + 2 NRTIs (PI group), 33 started first-generation INSTI (raltegravir or elvitegravir/cobicistat) + 2 NRTIs (INSTI-1 group), 58 started once-daily second-generation INSTI (dolutegravir or bictegravir) + 2 NRTIs (INSTI-2 group) and eight started other regimens. In the multivariate analysis, the INSTI-2 group showed similar or favourable outcomes compared with the PI group for viral suppression rates, time to viral suppression and time to viral rebound. Two cases in the INSTI-1 group experienced virological failure.

CONCLUSIONS

The general guideline recommendation of second-generation INSTI-based first-line ART for most PLWH is also applicable to PLWH harbouring E157Q.

摘要

背景

整合酶链转移抑制剂（INSTIs）是大多数指南推荐的 HIV 感染者（PLWH）一线抗逆转录病毒治疗（ART）药物。整合酶基因 HIV-1（人类免疫缺陷病毒 1 型）的 E157Q 耐药相关突变是一种高度流行（2%-5%）的多态性，关于其一线 ART 方案的最佳选择，目前仅有有限的数据。我们评估了 E157Q 阳性的 PLWH 在真实环境中应用各种一线 ART 方案的病毒学结局。

方法

一项多中心回顾性观察性研究，纳入了 2008 年至 2019 年间接受 ART 前整合酶基因耐药性检测并发现 E157Q 的 PLWH。比较了不同一线 ART 方案在 24 周和 48 周时的病毒抑制率（<50 拷贝/毫升）、病毒抑制时间和病毒反弹时间（≥100 拷贝/毫升）。

结果

在 4043 例 ART 初治的 PLWH 中，发现 E157Q 阳性者 167 例（4.1%）。其中 144 例在 ART 开始后有可用的临床数据，中位随访时间为 1888 天。45 例起始蛋白酶抑制剂+2 种 NRTIs（PI 组），33 例起始第一代 INSTI（raltegravir 或 elvitegravir/cobicistat）+2 种 NRTIs（INSTI-1 组），58 例起始每日 1 次的第二代 INSTI（dolutegravir 或 bictegravir）+2 种 NRTIs（INSTI-2 组），8 例起始其他方案。多变量分析显示，与 PI 组相比，INSTI-2 组在病毒抑制率、病毒抑制时间和病毒反弹时间方面具有相似或更优的结果。INSTI-1 组有 2 例出现病毒学失败。