Deng Yongyue, Wu Shouli, Qiu Lijun, Yan Yansheng
The School of Public Health, Fujian Medical University, Fuzhou, China; Department of Infectious Diseases, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China; Fujian Province Key Laboratory of Zoonosis Research, Fujian Center for Disease Control and Prevention, Fuzhou, China.
The School of Public Health, Fujian Medical University, Fuzhou, China; Fujian Province Key Laboratory of Zoonosis Research, Fujian Center for Disease Control and Prevention, Fuzhou, China.
Ann Palliat Med. 2021 Jul;10(7):7775-7785. doi: 10.21037/apm-21-1347.
It is largely unknown how frequently minor HIV drug-resistant variants at levels under limit of detection of conventional genotyping are present in patients experiencing virological failure (VF). Further, the clinical implications of minor drug-resistant variants at time of virologic failure are unknown.
Fifteen patients experiencing VF on a first-line regimen were evaluated by high-throughput sequencing and compared with the conventional Sanger genotype drug resistance detection method.
NRTI drug resistant mutations (DRMs) were detected in a high proportion of subjects, with the most common being M184V and TAMs. Minor resistant mutations accounted for 19.27% of the total drug-resistant mutations in patients with VF. A mean of 1.7 additional mutations per subject were detected by high-throughput sequencing, the difference was statistically significant, and those additional low-abundance drug-resistant mutations increased the genotypic resistance scores in 10 of 11 subjects (90.9%). Among persons experiencing VF, minor variants possessing major PI (protease inhibitor) DRMs were present in a minority of cases, which was also the case in ARV-naive subjects, and suggests PIs may be effective in subjects experiencing VF on subsequent second-line PI-based antiretroviral regimen. The high-throughput sequencing results of mutations between ART failure subjects and treatment naïve subjects were also compared. Three novel mutations were then screened with higher frequencies in the ART failure subjects.
It is important to guide the replacement of treatment programs and screening for new drug-resistant mutation sites, and the use of high-throughput sequencing methods can more comprehensively study the characteristics of drug-resistant viral variants of patients experiencing VF on a first-line regimen.
在病毒学失败（VF）的患者中，传统基因分型检测限以下水平的轻微HIV耐药变异的出现频率在很大程度上尚不清楚。此外，病毒学失败时轻微耐药变异的临床意义也不明确。
对15例一线治疗方案出现病毒学失败的患者进行高通量测序评估，并与传统的桑格基因型耐药检测方法进行比较。
在高比例的受试者中检测到核苷类逆转录酶抑制剂（NRTI）耐药突变（DRMs），最常见的是M184V和TAMs。轻微耐药突变占病毒学失败患者总耐药突变的19.27%。通过高通量测序，每个受试者平均检测到1.7个额外突变，差异具有统计学意义，并且那些额外的低丰度耐药突变使11名受试者中的10名（90.9%）的基因型耐药得分增加。在病毒学失败的患者中，少数病例存在具有主要蛋白酶抑制剂（PI）DRMs的轻微变异，初治抗逆转录病毒治疗（ART）的受试者也是如此，这表明PI可能对后续基于二线PI的抗逆转录病毒治疗方案出现病毒学失败的受试者有效。还比较了ART失败受试者和初治受试者之间突变的高通量测序结果。然后筛选出在ART失败受试者中频率较高的三个新突变。
指导治疗方案的更换和新耐药突变位点的筛查很重要，使用高通量测序方法可以更全面地研究一线治疗方案出现病毒学失败患者的耐药病毒变异特征。
