Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Laboratório de Medicina Laboratorial (LIM-03), São Paulo, São Paulo, Brazil.
Universidade de São Paulo, Faculdade de Medicina, Instituto de Medicina Tropical de São Paulo, São Paulo, São Paulo, Brazil.
Rev Inst Med Trop Sao Paulo. 2024 Jun 7;66:e35. doi: 10.1590/S1678-9946202466035. eCollection 2024.
The group-specific antigen (gag) plays a crucial role in the assembly, release, and maturation of HIV. This study aimed to analyze the partial sequence of the HIV gag gene to classify HIV subtypes, identify recombination sites, and detect protease inhibitor (PI) resistance-associated mutations (RAMs). The cohort included 100 people living with HIV (PLH) who had experienced antiretroviral treatment failure with reverse transcriptase/protease inhibitors. Proviral HIV-DNA was successfully sequenced in 96 out of 100 samples for gag regions, specifically matrix (p17) and capsid (p24). Moreover, from these 96 sequences, 82 (85.42%) were classified as subtype B, six (6.25%) as subtype F1, one (1.04%) as subtype C, and seven (7.29%) exhibited a mosaic pattern between subtypes B and F1 (B/F1), with breakpoints at p24 protein. Insertions and deletions of amino acid at p17 were observed in 51 samples (53.13%). The prevalence of PI RAM in the partial gag gene was observed in 78 out of 96 PLH (81.25%). Among these cases, the most common mutations were R76K (53.13%), Y79F (31.25%), and H219Q (14.58%) at non-cleavage sites, as well as V128I (10.42%) and Y132F (11.46%) at cleavage sites. While B/F1 recombination was identified in the p24, the p17 coding region showed higher diversity, where insertions, deletions, and PI RAM, were observed at high prevalence. In PLH with virological failure, the analysis of the partial gag gene could contribute to more accurate predictions in genotypic resistance to PIs. This can aid guide more effective HIV treatment strategies.
该研究旨在分析 HIV gag 基因的部分序列，对 HIV 进行亚型分类，识别重组位点，并检测蛋白酶抑制剂（PI）耐药相关突变（RAM）。该队列包括 100 名经历过逆转录酶/蛋白酶抑制剂失败的抗反转录病毒治疗的 HIV 感染者（PLH）。在 100 个样本中，有 96 个成功对 gag 区（p17 和 p24）进行了 HIV 前病毒 DNA 测序。此外，从这 96 个序列中，82 个（85.42%）被归类为 B 亚型，6 个（6.25%）为 F1 亚型，1 个（1.04%）为 C 亚型，7 个（7.29%）显示 B 和 F1 之间的嵌合模式（B/F1），在 p24 蛋白处存在断点。在 51 个样本（53.13%）中观察到 p17 氨基酸的插入和缺失。在 96 个 PLH 中有 78 个（81.25%）在部分 gag 基因中观察到 PI RAM。在这些病例中，最常见的突变是非切割位点的 R76K（53.13%）、Y79F（31.25%）和 H219Q（14.58%），以及切割位点的 V128I（10.42%）和 Y132F（11.46%）。虽然在 p24 中发现了 B/F1 重组，但 p17 编码区显示出更高的多样性，其中观察到高流行率的插入、缺失和 PI RAM。在病毒学失败的 PLH 中，对部分 gag 基因的分析有助于更准确地预测对 PI 的基因型耐药。这有助于指导更有效的 HIV 治疗策略。
