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. 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. 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. 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.

中文翻译：

---

耐药性在南非农村地区病毒抑制不良中的作用：基于人群的研究结果。

了解导致病毒学失败的因素，包括 HIV 耐药突变 (DRM) 的影响，对于确保 HIV 治疗保持有效至关重要。我们在南非农村地区进行的一项基于人群的血清流行率调查中，研究了耐药突变对艾滋病毒阳性参与者低病毒抑制的影响。我们对参加 2014 年西北省一项调查的 HIV 阳性成年人的干血斑 (DBS) 进行了 HIV 耐药基因分型和 ART 分析物检测。在病毒学失败的患者中（> 5000 拷贝/mL），我们描述了蛋白酶抑制剂 (PI)、核苷逆转录酶抑制剂 (NRTI) 和非核苷逆转录酶抑制剂 (NNRTI) 的 DRM 频率，报告了耐药性与抗逆转录病毒药物的关联治疗（ART）状态，并评估对一线和二线治疗的耐药性。对分析进行加权以考虑抽样设计。对总共 170 个 DBS 样本进行了病毒载量和 ART 分析物的检测；78.4% 的男性和 50.0% 的女性有病毒学失败的证据，并进行了耐药性评估，并对 76/107 个样本进行了成功测序。我们发现 22% 的参与者存在 ≥1 DRM；47% 来自可检测分析物（依非韦伦、奈韦拉平或洛匹那韦）的样品。在具有 DRM 和可检测分析物的患者中，60% 表现出高水平耐药性，并且对一线和二线治疗方案中通常使用的 ≥1 NRTI/NNRTI 的预测病毒学应答降低。在南非农村人口样本中，接触 ART 的成年人中 DRM 和预测的一线和二线治疗敏感性降低很常见。结果强调了持续病毒学监测、方案优化和依从性咨询对于优化持久病毒学抑制的重要性。