HIV 感染者中紧急出现的多替拉韦耐药突变的流行情况：快速范围综述。

Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review.

机构信息

Department of Family and Community Medicine, University of California San Francisco, San Francisco, CA 94110, USA.

Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA.

出版信息

Viruses. 2024 Mar 4;16(3):399. doi: 10.3390/v16030399.

DOI:10.3390/v16030399

PMID:38543764

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10975848/

Abstract

BACKGROUND

Dolutegravir (DTG) is a cornerstone of global antiretroviral (ARV) therapy (ART) due to its high efficacy and favorable tolerability. However, limited data exist regarding the risk of emergent integrase strand transfer inhibitor (INSTI) drug-resistance mutations (DRMs) in individuals receiving DTG-containing ART.

METHODS

We performed a PubMed search using the term "Dolutegravir", last updated 18 December 2023, to estimate the prevalence of VF with emergent INSTI DRMs in people living with HIV (PLWH) without previous VF on an INSTI who received DTG-containing ART.

RESULTS

Of 2131 retrieved records, 43 clinical trials, 39 cohorts, and 6 cross-sectional studies provided data across 6 clinical scenarios based on ART history, virological status, and co-administered ARVs: (1) ART-naïve PLWH receiving DTG plus two NRTIs; (2) ART-naïve PLWH receiving DTG plus lamivudine; (3) ART-experienced PLWH with VF on a previous regimen receiving DTG plus two NRTIs; (4) ART-experienced PLWH with virological suppression receiving DTG plus two NRTIs; (5) ART-experienced PLWH with virological suppression receiving DTG and a second ARV; and (6) ART-experienced PLWH with virological suppression receiving DTG monotherapy. The median proportion of PLWH in clinical trials with emergent INSTI DRMs was 1.5% for scenario 3 and 3.4% for scenario 6. In the remaining four trial scenarios, VF prevalence with emergent INSTI DRMs was ≤0.1%. Data from cohort studies minimally influenced prevalence estimates from clinical trials, whereas cross-sectional studies yielded prevalence data lacking denominator details.

CONCLUSIONS

In clinical trials, the prevalence of VF with emergent INSTI DRMs in PLWH receiving DTG-containing regimens has been low. Novel approaches are required to assess VF prevalence with emergent INSTI DRMs in PLWH receiving DTG in real-world settings.

摘要

背景

由于高效且耐受性良好，多拉韦林（DTG）是全球抗逆转录病毒（ARV）治疗（ART）的基石。然而，在接受含 DTG 的 ART 的个体中，关于出现整合酶抑制剂（INSTI）耐药突变（DRMs）的风险的数据有限。

方法

我们使用术语“Dolutegravir”在 PubMed 上进行了搜索，最后更新日期为 2023 年 12 月 18 日，以估计在没有先前 INSTI 病毒学失败史的接受含 DTG 的 ART 的 HIV 感染者（PLWH）中，出现紧急 INSTI DRMs 的病毒学失败（VF）的流行率。

结果

在 2131 条检索记录中，有 43 项临床试验、39 项队列研究和 6 项横断面研究提供了 6 种基于 ART 史、病毒学状态和联合使用的 ARV 的临床情况的数据：（1）接受 DTG 加两种 NRTI 的 ART 初治 PLWH；（2）接受 DTG 加拉米夫定的 ART 初治 PLWH；（3）先前方案 VF 的 ART 经验丰富的 PLWH，接受 DTG 加两种 NRTI；（4）病毒学抑制的 ART 经验丰富的 PLWH，接受 DTG 加两种 NRTI；（5）病毒学抑制的接受 DTG 和第二种 ARV 的 ART 经验丰富的 PLWH；和（6）病毒学抑制的接受 DTG 单药治疗的 ART 经验丰富的 PLWH。在临床试验中，出现紧急 INSTI DRMs 的 PLWH 的比例中位数为 3 号方案中的 1.5%，6 号方案中的 3.4%。在其余四个试验方案中，出现紧急 INSTI DRMs 的 VF 流行率≤0.1%。队列研究的数据对临床试验的流行率估计影响不大，而横断面研究则提供了缺乏分母细节的流行率数据。