Moreno Ambar, González Claudia, Góndola Jessica, Chavarría Oris, Ortiz Alma, Castillo Jorge, Castillo Mewa Juan, Pascale Juan Miguel, Martínez Alexander Augusto
Department of Research in Genomics and Proteomics, Gorgas Memorial Institute for Health Studies, Panama City 0816-02593, Panama.
Department of Microbiology and Immunology, University of Panama, Panama City 3366, Panama.
Infect Dis Rep. 2023 Aug 1;15(4):436-444. doi: 10.3390/idr15040044.
Low-frequency mutations associated with drug resistance have been related to virologic failure in subjects with no history of pre-treatment and recent HIV diagnosis. In total, 78 antiretroviral treatment (ART)-naïve subjects with a recent HIV diagnosis were selected and followed by CD4+ T lymphocytes and viral load tests to detect virologic failure. We sequenced the basal samples retrospectively using next-generation sequencing (NGS), looking for low-frequency mutations that had not been detected before using the Sanger sequencing method (SSM) and describing the response to ART. Twenty-two subjects developed virologic failure (VF), and thirteen of them had at least one drug-resistance mutation associated with Reverse Transcriptase Inhibitors (RTI) and Protease Inhibitors (PIs) at frequency levels ≤ 1%, not detected previously in their basal genotyping test. No resistance mutations were observed to Integrase Strand Transfer Inhibitors (INSTIs). We identified a possible cause of VF in ART-naïve subjects with low-frequency mutations detected. To our knowledge, this is the first evaluation of pre-existing drug resistance for HIV-1 minority variants carried out on ART-naïve people living with HIV/AIDS (PLWHA) by analyzing the HIV-1 gene using NGS in the country.
与耐药性相关的低频突变与既往无治疗史且近期诊断为HIV的受试者的病毒学失败有关。总共选取了78例近期诊断为HIV的初治抗逆转录病毒治疗(ART)受试者,并通过CD4+T淋巴细胞和病毒载量检测进行随访,以检测病毒学失败情况。我们使用下一代测序(NGS)对基础样本进行回顾性测序,寻找之前使用桑格测序法(SSM)未检测到的低频突变,并描述对ART的反应。22名受试者出现病毒学失败(VF),其中13人在频率水平≤1%时至少有一个与逆转录酶抑制剂(RTI)和蛋白酶抑制剂(PI)相关的耐药突变,在其基础基因分型检测中此前未检测到。未观察到对整合酶链转移抑制剂(INSTI)的耐药突变。我们确定了在检测到低频突变的初治受试者中VF的一个可能原因。据我们所知,这是该国首次通过使用NGS分析HIV-1基因,对HIV-1少数变异的既往耐药性在初治HIV/AIDS患者(PLWHA)中进行评估。