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博茨瓦纳在接受联合抗逆转录病毒治疗(ART)时低病毒血症个体中的 HIV-1 耐药突变。

HIV-1 drug resistance mutations among individuals with low-level viraemia while taking combination ART in Botswana.

机构信息

Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.

School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana.

出版信息

J Antimicrob Chemother. 2022 Apr 27;77(5):1385-1395. doi: 10.1093/jac/dkac056.

DOI:10.1093/jac/dkac056
PMID:35229102
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9633723/
Abstract

OBJECTIVES

To assess whether a single instance of low-level viraemia (LLV) is associated with the presence of drug resistance mutations (DRMs) and predicts subsequent virological failure (VF) in adults receiving ART in 30 communities participating in the Botswana Combination Prevention Project.

METHODS

A total of 6078 HIV-1 C pol sequences were generated and analysed using the Stanford HIV drug resistance database. LLV was defined as plasma VL = 51-999 copies/mL and VF was defined as plasma VL ≥ 1000 copies/mL.

RESULTS

Among 6078 people with HIV (PWH), 4443 (73%) were on ART for at least 6 months. Of the 332 persons on ART with VL > 50 copies/mL, 175 (4%) had VL ≥ 1000 copies/mL and 157 (4%) had LLV at baseline. The prevalence of any DRM was 57 (36%) and 78 (45%) in persons with LLV and VL ≥ 1000 copies/mL, respectively. Major DRMs were found in 31 (20%) with LLV and 53 (30%) with VL ≥ 1000 copies/mL (P = 0.04). Among the 135 PWH with at least one DRM, 17% had NRTI-, 35% NNRTI-, 6% PI- and 3% INSTI-associated mutations. Among the 3596 participants who were followed up, 1709 (48%) were on ART for ≥6 months at entry and had at least one subsequent VL measurement (median 29 months), 43 (3%) of whom had LLV. The OR of experiencing VF in persons with LLV at entry was 36-fold higher than in the virally suppressed group.

CONCLUSIONS

A single LLV measurement while on ART strongly predicted the risk of future VF, suggesting the use of VL > 50 copies/mL as an indication for more intensive adherence support with more frequent VL monitoring.

摘要

目的

评估单次低水平病毒血症 (LLV) 是否与耐药突变 (DRMs) 的存在有关,并预测在博茨瓦纳组合预防项目参与的 30 个社区中接受抗逆转录病毒治疗 (ART) 的成年人中随后发生病毒学失败 (VF)。

方法

共生成了 6078 个 HIV-1 C pol 序列,并使用斯坦福 HIV 药物耐药性数据库进行分析。LLV 定义为血浆 VL = 51-999 拷贝/ml,VF 定义为血浆 VL ≥ 1000 拷贝/ml。

结果

在 6078 名 HIV 感染者 (PWH) 中,4443 名 (73%) 接受 ART 治疗至少 6 个月。在 332 名 VL>50 拷贝/ml 的接受 ART 治疗的人中,175 名 (4%) VL≥1000 拷贝/ml,157 名 (4%)基线时存在 LLV。LLV 和 VL≥1000 拷贝/ml 的人分别有 57 (36%) 和 78 (45%) 存在任何 DRM。在有 LLV 的人中发现了 31 种 (20%) 主要 DRM 和在 VL≥1000 拷贝/ml 的人中发现了 53 种 (30%) (P=0.04)。在至少有一种 DRM 的 135 名 PWH 中,17%有 NRTI-、35%有 NNRTI-、6%有 PI-和 3%有 INSTI-相关突变。在 3596 名随访参与者中,1709 名 (48%) 在进入时接受 ART 治疗至少 6 个月,并至少有一次后续 VL 测量 (中位数 29 个月),其中 43 名 (3%) 有 LLV。在进入时存在 LLV 的人发生 VF 的 OR 是病毒抑制组的 36 倍。

结论

在接受 ART 治疗时单次 LLV 测量强烈预测未来 VF 的风险,这表明使用 VL>50 拷贝/ml 作为更频繁 VL 监测的更密集依从性支持的指征。

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