两种与三种整合酶抑制剂方案在病毒学抑制的 HIV 感染患者中的疗效和持久性：来自真实世界 ODOACRE 队列的数据。

Efficacy and durability of two- vs. three-drug integrase inhibitor-based regimens in virologically suppressed HIV-infected patients: Data from real-life ODOACRE cohort.

机构信息

UOC Malattie Infettive e Tropicali, Azienda Ospedaliero-Universitaria Senese, Siena, Italy.

UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.

出版信息

HIV Med. 2021 Oct;22(9):843-853. doi: 10.1111/hiv.13146. Epub 2021 Jul 27.

DOI:10.1111/hiv.13146

PMID:34318591

Abstract

OBJECTIVES

The aim of the present study was to compare the efficacy and durability of treatment switch to two-drug (2DR) vs. three-drug (3DR) integrase inhibitor (InSTI)-based regimens in a real-life setting.

METHODS

Within the ODOACRE cohort, we selected adult patients with HIV RNA < 50 copies/mL switching to an InSTI-based 2DR or 3DR. Survival analyses were performed to estimate the probability of virological failure (VF, defined as one HIV RNA > 1000 copies/mL or two consecutive HIV RNA > 50 copies/mL) and treatment discontinuation (TD, defined as any modification, intensification or interruption of the regimen), and to evaluate their predictors.

RESULTS

Overall, 1666 patients were included, of whom 1334 (80%) were treated with a 3DR (19.9%, 25.0% and 55.1% elvitegravir-, raltegravir- and dolutegravir-based, respectively) and 332 (20%) with a 2DR (79.2% dolutegravir + lamivudine and 20.8% dolutegravir + rilpivirine). Over a median (interquartile range) follow-up of 100 (52-150) weeks, 52 (3.1%) patients experienced VF with an incidence of 1.5/100 person-year of follow-up (PYFU). The estimated 96-week probability of VF was similar for the 2DR and 3DR groups (2.3% vs. 2.8%, P = 0.53), but it was higher for elvitegravir (4.9%) and raltegravir (5.0%) than for dolutegravir (1.5%) (P = 0.04). Four hundred (24%) patients discontinued their InSTI-based regimen, with an incidence of 11.3/100 PYFU. At 96 weeks, 3DRs showed a higher probability of TD for any reason (20.6% vs. 11.2%, P < 0.001) and TD for toxicity (9.0% vs. 6.6%, P = 0.02) when compared with 2DRs. A higher risk of TD for central nervous system toxicity was observed for dolutegravir than for elvitegravir and raltegravir (4.0% vs. 2.5% vs. 0.6%, P = 0.005).

CONCLUSIONS

In virologically suppressed HIV-infected patients, 2DRs showed an efficacy similar to 3DRs but with better tolerability.

摘要

目的

本研究旨在比较真实环境中治疗转换为二药（2DR）与三药（3DR）整合酶抑制剂（InSTI）方案治疗的疗效和持久性。

方法

在 ODOACRE 队列中，我们选择了 HIV RNA < 50 拷贝/mL 的接受 InSTI 为基础的 2DR 或 3DR 治疗转换的成年患者。进行生存分析以估计病毒学失败（VF，定义为 HIV RNA > 1000 拷贝/mL 或连续两次 HIV RNA > 50 拷贝/mL）和治疗停药（TD，定义为任何方案修改、强化或中断）的概率，并评估其预测因素。

结果

总体而言，纳入了 1666 例患者，其中 1334 例（80%）接受 3DR（依韦替格拉韦、拉替拉韦和多替拉韦分别为 19.9%、25.0%和 55.1%）治疗，332 例（20%）接受 2DR（96.8%为多替拉韦+拉米夫定，20.8%为多替拉韦+利匹韦林）治疗。在中位（四分位间距）100（52-150）周的随访中，52 例（3.1%）患者发生 VF，发生率为 1.5/100 人年随访（PYFU）。2DR 和 3DR 组 96 周时的 VF 估计概率相似（2.3% vs. 2.8%，P=0.53），但依韦替格拉韦（4.9%）和拉替拉韦（5.0%）的概率高于多替拉韦（1.5%）（P=0.04）。400 例（24%）患者因任何原因停止了他们的 InSTI 方案治疗，发生率为 11.3/100 PYFU。96 周时，3DR 组因任何原因（20.6% vs. 11.2%，P < 0.001）和因毒性（9.0% vs. 6.6%，P=0.02）停药的概率均高于 2DR 组。与依韦替格拉韦和拉替拉韦相比，多替拉韦发生中枢神经系统毒性停药的风险更高（4.0% vs. 2.5% vs. 0.6%，P=0.005）。