在博茨瓦纳弗朗西斯敦接受基于多替拉韦的抗逆转录病毒治疗的艾滋病毒感染者中，逆转录酶抑制剂相关耐药突变的高流行率。

High prevalence of reverse transcriptase inhibitors associated resistance mutations among people living with HIV on dolutegravir-based antiretroviral therapy in Francistown, Botswana.

作者信息

Choga Ontlametse T, Lemogang Goitseone M, Choga Wonderful T, Muzanywa Gaonyadiwe, Shadreck Thembinkosi M, Ralegoreng Charity, Maruapula Dorcas, Moraka Natasha O, Koofhethile Catherine K, Mokgethi Patrick T, Seru Kedumetse, Zuze Boitumelo J L, Montshosi Patience, Gobe Irene, Motswaledi Modisa S, Musonda Rosemary, Mbulawa Mpaphi B, Makhema Joseph, Shapiro Roger, Lockman Shahin, Chebani Tony, Nawa Judith, Bochena Lindani, Moyo Sikhulile, Gaseitsiwe Simani

机构信息

Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana.

Department of Medical Sciences, Faculty of Allied Health Professions, University of Botswana, Gaborone, Botswana.

出版信息

J Antimicrob Chemother. 2025 Mar 3;80(3):767-776. doi: 10.1093/jac/dkae472.

DOI:10.1093/jac/dkae472

PMID:39764689

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11879200/

Abstract

OBJECTIVES

We assessed HIV-1 drug resistance profiles among people living with HIV (PLWH) with detectable viral load (VL) and on dolutegravir-based antiretroviral therapy (ART) in Botswana.

METHODS

The study utilised available 100 residual HIV-1 VL samples from unique PLWH in Francistown who had viraemia at-least 6 months after initiating ART in Botswana's national ART program from November 2023 to January 2024. Viraemia was categorized as low-level viraemia (LLV) (VL: 200-999 copies/mL) or virologic failure (VF) (VL ≥1000 copies/mL). HIV-1 protease, reverse transcriptase and integrase genes were sequenced using an in-house next-generation sequencing Oxford nanopore technology. HIV-1 drug resistance mutations (DRMs) were identified using the HIVdb Program in the Stanford HIV drug resistance database and compared between VL groups.

RESULTS

Among 100 participants, 83.0% were on dolutegravir-based, 10.0% were on non-dolutegravir-based ART and 7.0% had unknown/undocumented ART regimens. Thirty (30%) participants had LLV and 70 (70%) had VF. Among 58 successfully sequenced, 32.8% [95% Confidence Interval (CI): 21.8-46.0] had DRMs to any drug class, 33.3% (4/12) in the LLV group and 32.6% (15/46) in the VF group. Among individuals on dolutegravir-based ART, the overall HIV DRMs were 34.8% (95% CI: 22.7-49.2). By VL groups, 40.0% (95% CI: 16.8-68.7) and 33.3% (95% CI: 20.2-50.0) had DRMs at LLV and VF, respectively.

CONCLUSIONS

A high but similar prevalence of any DRMs was observed among individuals with LLV and those with VF on dolutegravir-based therapy. Monitoring DRMs in individuals with detectable VL is crucial for preserving dolutegravir-based ART.

摘要

目的

我们评估了博茨瓦纳病毒载量（VL）可检测且接受基于多替拉韦的抗逆转录病毒疗法（ART）的艾滋病病毒感染者（PLWH）中的HIV-1耐药谱。

方法

该研究利用了2023年11月至2024年1月期间在博茨瓦纳国家ART项目中，在弗朗西斯敦开始ART后至少6个月出现病毒血症的100例独特PLWH的可用残留HIV-1 VL样本。病毒血症分为低水平病毒血症（LLV）（VL：200 - 999拷贝/毫升）或病毒学失败（VF）（VL≥1000拷贝/毫升）。使用内部下一代测序牛津纳米孔技术对HIV-1蛋白酶、逆转录酶和整合酶基因进行测序。使用斯坦福HIV耐药数据库中的HIVdb程序识别HIV-1耐药突变（DRM），并在VL组之间进行比较。

结果

在100名参与者中，83.0%接受基于多替拉韦的治疗，10.0%接受非多替拉韦的ART，7.0%的ART方案未知/未记录。30名（30%）参与者有LLV，70名（70%）有VF。在58例成功测序的样本中，32.8%[95%置信区间（CI）：21.8 - 46.0]对任何药物类别有DRM，LLV组为33.3%（4/12），VF组为32.6%（15/46）。在接受基于多替拉韦的ART的个体中，总体HIV DRM为34.8%（95%CI：22.7 - 49.2）。按VL组划分，LLV和VF时分别有40.0%（95%CI：16.8 - 68.7）和33.3%（95%CI：20.2 - 50.0）有DRM。