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博茨瓦纳非公民艾滋病毒感染者中治疗前和获得性艾滋病毒-1耐药突变的高流行率。

High prevalence of pre-treatment and acquired HIV-1 drug resistance mutations among non-citizens living with HIV in Botswana.

作者信息

Mokgethi Patrick T, Choga Wonderful T, Maruapula Dorcas, Moraka Natasha O, Seatla Kaelo K, Bareng Ontlametse T, Ditshwanelo Doreen D, Mulenga Graceful, Mohammed Terence, Kaumba Pearl M, Chihungwa Moses, Marukutira Tafireyi, Moyo Sikhulile, Koofhethile Catherine K, Dickinson Diana, Mpoloka Sununguko W, Gaseitsiwe Simani

机构信息

Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.

Department of Biological Sciences, University of Botswana, Gaborone, Botswana.

出版信息

Front Microbiol. 2024 Feb 20;15:1338191. doi: 10.3389/fmicb.2024.1338191. eCollection 2024.

DOI:10.3389/fmicb.2024.1338191
PMID:38476948
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10929613/
Abstract

BACKGROUND

Approximately 30,000 non-citizens are living with HIV in Botswana, all of whom as of 2020 are eligible to receive free antiretroviral treatment (ART) within the country. We assessed the prevalence of HIV-1 mutational profiles [pre-treatment drug resistance (PDR) and acquired drug resistance (ADR)] among treatment-experienced (TE) and treatment-naïve (TN) non-citizens living with HIV in Botswana.

METHODS

A total of 152 non-citizens living with HIV were enrolled from a migrant HIV clinic at Independence Surgery, a private practice in Botswana from 2019-2021. Viral RNA isolated from plasma samples were genotyped for HIV drug resistance (HIVDR) using Sanger sequencing. Major known HIV drug resistance mutations (DRMs) in the region were determined using the Stanford HIV Drug Resistance Database. The proportions of HIV DRMs amongst TE and TN non-citizens were estimated with 95% confidence intervals (95% CI) and compared between the two groups.

RESULTS

A total of 60/152 (39.5%) participants had a detectable viral load (VL) >40 copies/mL and these were included in the subsequent analyses. The median age at enrollment was 43 years (Q1, Q3: 38-48). Among individuals with VL > 40 copies/mL, 60% (36/60) were treatment-experienced with 53% (19/36) of them on Atripla. Genotyping had a 62% (37/60) success rate - 24 were TE, and 13 were TN. A total of 29 participants (78.4, 95% CI: 0.12-0.35) had major HIV DRMs, including at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) associated DRM. In TE individuals, ADR to any antiretroviral drug was 83.3% (20/24), while for PDR was 69.2% (9/13). The most frequent DRMs were nucleoside reverse transcriptase inhibitors (NRTIs) M184V (62.1%, 18/29), NNRTIs V106M (41.4%, 12/29), and K103N (34.4%, 10/29). No integrase strand transfer inhibitor-associated DRMs were reported.

CONCLUSION

We report high rates of PDR and ADR in ART-experienced and ART-naïve non-citizens, respectively, in Botswana. Given the uncertainty of time of HIV acquisition and treatment adherence levels in this population, routine HIV-1C VL monitoring coupled with HIVDR genotyping is crucial for long-term ART success.

摘要

背景

在博茨瓦纳,约有30000名非公民感染了艾滋病毒,截至2020年,他们所有人都有资格在该国接受免费抗逆转录病毒治疗(ART)。我们评估了博茨瓦纳有治疗经验(TE)和无治疗经验(TN)的感染艾滋病毒的非公民中HIV-1突变谱[治疗前耐药性(PDR)和获得性耐药性(ADR)]的流行情况。

方法

2019年至2021年期间,从博茨瓦纳一家私人诊所独立外科的移民艾滋病毒诊所招募了152名感染艾滋病毒的非公民。使用桑格测序法对从血浆样本中分离的病毒RNA进行艾滋病毒耐药性(HIVDR)基因分型。使用斯坦福艾滋病毒耐药数据库确定该区域主要的已知艾滋病毒耐药突变(DRM)。估计TE和TN非公民中艾滋病毒DRM的比例,并给出95%置信区间(95%CI),然后在两组之间进行比较。

结果

共有60/152(39.5%)名参与者的病毒载量(VL)>40拷贝/mL且可检测到,这些人被纳入后续分析。入组时的中位年龄为43岁(第一四分位数,第三四分位数:38 - 48岁)。在VL>40拷贝/mL的个体中,60%(36/60)有治疗经验,其中53%(19/36)正在服用依法韦仑/恩曲他滨/替诺福韦复方制剂(Atripla)。基因分型成功率为62%(37/60)——24名有治疗经验,13名无治疗经验。共有29名参与者(78.4,95%CI:0.12 - 0.35)有主要的艾滋病毒DRM,包括至少一种与非核苷类逆转录酶抑制剂(NNRTI)相关的DRM。在有治疗经验的个体中,对任何抗逆转录病毒药物的获得性耐药率为83.3%(20/24),而治疗前耐药率为69.2%(9/13)。最常见的DRM是核苷类逆转录酶抑制剂(NRTI)M184V(62.1%,18/29)、NNRTI V106M(41.4%,12/29)和K103N(34.4%,10/2)。未报告与整合酶链转移抑制剂相关的DRM。

结论

我们报告了博茨瓦纳有ART治疗经验和无ART治疗经验的非公民中分别有较高的PDR和ADR率。鉴于该人群感染艾滋病毒的时间和治疗依从性水平存在不确定性,常规的HIV-1C VL监测以及HIVDR基因分型对于长期ART治疗成功至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6936/10929613/6132003039d1/fmicb-15-1338191-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6936/10929613/c827f2e612ed/fmicb-15-1338191-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6936/10929613/6132003039d1/fmicb-15-1338191-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6936/10929613/c827f2e612ed/fmicb-15-1338191-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6936/10929613/6132003039d1/fmicb-15-1338191-g002.jpg

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