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耐药性在南非农村地区病毒抑制不佳中的作用:基于人群的研究结果。

The role of drug resistance in poor viral suppression in rural South Africa: findings from a population-based study.

机构信息

Division of Prevention Science, Department of Medicine, University of California San Francisco, 550 16th Street, 3rd Floor, San Francisco, CA, 94158-2549, USA.

Department of Epidemiology, University of California San Francisco, San Francisco, USA.

出版信息

BMC Infect Dis. 2020 Mar 26;20(1):248. doi: 10.1186/s12879-020-4933-z.

Abstract

BACKGROUND

Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa.

METHODS

We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province. Among those with virologic failure (> 5000 copies/mL), we describe frequency of DRM to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI), report association of resistance with antiretroviral therapy (ART) status, and assess resistance to first and second line therapy. Analyses are weighted to account for sampling design.

RESULTS

Overall 170 DBS samples were assayed for viral load and ART analytes; 78.4% of men and 50.0% of women had evidence of virologic failure and were assessed for drug resistance, with successful sequencing of 76/107 samples. We found ≥1 DRM in 22% of participants; 47% were from samples with detectable analyte (efavirenz, nevirapine or lopinavir). Of those with DRM and detectable analyte, 60% showed high-level resistance and reduced predicted virologic response to ≥1 NRTI/NNRTI typically used in first and second-line regimens.

CONCLUSIONS

DRM and predicted reduced susceptibility to first and second-line regimens were common among adults with ART exposure in a rural South African population-based sample. Results underscore the importance of ongoing virologic monitoring, regimen optimization and adherence counseling to optimize durable virologic suppression.

摘要

背景

了解导致病毒学失败的因素,包括 HIV 耐药突变(DRM)的贡献,对于确保 HIV 治疗仍然有效至关重要。我们研究了在南非农村进行的一项基于人群的血清流行率调查中,HIV 阳性参与者中耐药突变对病毒载量抑制不佳的影响。

方法

我们对参加 2014 年西北省调查的 HIV 阳性成年人的干血斑(DBS)进行 HIV 耐药基因分型和 ART 分析物检测。在病毒学失败(>5000 拷贝/ml)的患者中,我们描述了对蛋白酶抑制剂(PI)、核苷逆转录酶抑制剂(NRTI)和非核苷逆转录酶抑制剂(NNRTI)的耐药突变频率,报告了耐药性与抗逆转录病毒治疗(ART)状态的关系,并评估了对一线和二线治疗的耐药性。分析结果经过加权处理以考虑采样设计。

结果

共对 170 份 DBS 样本进行了病毒载量和 ART 分析物检测;78.4%的男性和 50.0%的女性出现病毒学失败,并对耐药性进行了评估,其中 76/107 份样本成功进行了测序。我们发现 22%的参与者存在至少一种耐药突变;47%来自可检测分析物(依非韦伦、奈韦拉平或洛匹那韦)的样本。在有 DRM 和可检测分析物的患者中,60%表现出高水平耐药性,对一线和二线方案中常用的至少 1 种 NRTI/NNRTI 的预测病毒学反应降低。

结论

在南非农村基于人群的样本中,接受 ART 治疗的成年人中,耐药突变和对一线和二线方案的预测敏感性降低较为常见。研究结果强调了持续进行病毒学监测、方案优化和依从性咨询以优化持久病毒学抑制的重要性。

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