Feasibility and clinical relevance of HIV-1 drug resistance testing in patients with low-level viraemia in South Africa
Feasibility and clinical relevance of HIV-1 drug resistance testing in patients with low-level viraemia in South Africa
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DOI：
10.1093/jac/dkab220
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发表时间：
2021-07-19
影响因子：
5.2
通讯作者：
Steegen, Kim
中科院分区：
文献类型：
--
作者：
Bangalee, Avania;Hans, Lucia;Steegen, Kim
目的：为了确定在南非人群中使用内部检测方法在低水平病毒血症（LLV）下进行HIV基因分型的可行性以及该人群中耐药（HIV DR）的患病率和临床相关性。我们进行了一次观察性的回顾性的，对2017年8月至2018年10月在约翰内斯堡公共部门实验室进行常规HIV DR检测的LLV患者样本进行的队列研究2018.采用巢式RT-PCR和桑格测序进行基因分型。针对不同病毒血症类别评价基因分型成功率。结果：分析了159例HIV-1感染者、治疗经验丰富的成人LLV（5- 999 copies/mL）的血浆样本。内部试验表现良好，总体成功率为78.6%（125/159，95% CI 71.6-84.3）。LLV队列中耐药突变的患病率为79.2%（99/125，95% CI 71.2-85.4），大多数患者（n=109，68.6%）在基因分型时接受基于PI的方案。在获得的125个序列中，73.6%（92/125）的序列具有>= 1个NRTI突变，而70.4%（88/125）的序列具有>= 1个NNRTI突变。主要PI突变，包括M46 I和V82 A，检测到7.2%（9/125）的patients.Conclusions：目前南非病毒学失败的指导方针可能会让病人失败的方案比必要的时间更长。我们的数据表明，在LLV基因分型是可行的，实施可能会导致早期识别和转诊的患者需要三线治疗方案。
Objectives: To determine the feasibility of HIV genotyping at low-level viraemia (LLV) using an in-house assay in a South African population and the prevalence, as well as the clinical relevance, of drug resistance (HIVDR) in this population.Methods: We conducted an observational, retrospective, cohort study on patient samples with LLV referred for routine HIVDR testing at a public sector Johannesburg laboratory from August 2017 to October 2018. Genotyping was performed using a nested RT-PCR assay and Sanger sequencing. The genotyping success rate was evaluated for different viraemia categories. Sequences were loaded onto the Stanford HIVdb genotypic resistance tool (version 8.7) for drug resistance interpretation.Results: Plasma samples from 159 HIV-1-infected, treatment-experienced adults with LLV (5-999copies/mL) were analysed. The in-house assay performed well with an overall success rate of 78.6% (125/159, 95% CI 71.6-84.3). The prevalence of drug resistance mutations in the LLV cohort was 79.2% (99/125, 95% CI 71.2-85.4) with most patients (n=109, 68.6%) on a PI-based regimen at the time of genotyping. Of 125 sequences obtained, 73.6% (92/125) had >= 1 NRTI mutation while 70.4% (88/125) had >= 1 NNRTI mutation. Major PI mutations, including M46I and V82A, were detected in 7.2% (9/125) of patients.Conclusions: Current South African virological failure guidelines may keep patients on failing regimens for longer than necessary. Our data suggest that genotyping at LLV is feasible and implementation could result in earlier identification and referral of patients requiring third-line regimens.