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解析 HIV-1 患者 V3 环中是否存在巴西 GWGR 基序对长期 cART 治疗临床结局的影响。

Unraveling clinical outcomes of long-term cART treatment in HIV-1 patients with or without the Brazilian GWGR motif in the V3 loop.

机构信息

Universidade de São Paulo, Faculdade de Medicina, Instituto de Medicina Tropical de São Paulo, Laboratório de Investigação Médica (LIM-56), São Paulo, São Paulo, Brazil.

Universidade Federal de São Paulo, Laboratório de Retrovirologia, São Paulo, São Paulo, Brazil.

出版信息

Rev Inst Med Trop Sao Paulo. 2024 Jul 8;66:e38. doi: 10.1590/S1678-9946202466038. eCollection 2024.

DOI:10.1590/S1678-9946202466038
PMID:39052025
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11251515/
Abstract

The presence of genetic mutations in HIV poses a significant challenge, potentially leading to antiretroviral resistance and hampering therapeutic development. The Brazilian population has presented variations in the HIV envelope V3 loop gene, especially the GWGR motif. This motif has been linked to reduced transmission potential and slower CD4+ T cell decline. This study aimed to assess clinical outcomes in patients with HIV-1 infected with strains containing the GWGR motif compared with those without it during long-term cART. A cohort of 295 patients with HIV was examined for the GWGR motif presence in the V3 loop. A total of 58 samples showed the GWGR signature, while 237 had other signatures. Multifactorial analyses showed no significant differences in demographic characteristics, CD4+ cell count, AIDS progression, or mortality between GWGR carriers and others. However, the mean interval between the first positive HIV test and the initial AIDS-defining event was more than two times longer for women carrying the GWGR signature (p = 0.0231). We emphasize the positive impact of cART on HIV/AIDS treatment, including viral suppression, CD4+ cell preservation, and immune function maintenance. Although no significant differences were found during cART, residual outcomes reflecting adherence challenges were observed between diagnosis and the first AIDS-defining event. The previously described outcomes, highlighting statistically significant differences between individuals carrying the GPGR motif compared with those with the Brazilian GWGR motif, may be directly linked to the natural progression of infection before advancements in cART. Presently, these physicochemical aspects may no longer hold the same relevance.

摘要

HIV 中存在的基因突变带来了重大挑战,可能导致抗逆转录病毒耐药性,并阻碍治疗方法的发展。巴西人群的 HIV 包膜 V3 环基因存在变异,特别是 GWGR 基序。该基序与降低传播潜力和减缓 CD4+T 细胞下降有关。本研究旨在评估在长期 cART 期间,感染含有 GWGR 基序的 HIV-1 株的患者与未感染的患者的临床结局。对 295 例 HIV 患者进行了 V3 环 GWGR 基序存在的评估。共有 58 个样本显示出 GWGR 特征,而 237 个样本则显示出其他特征。多因素分析显示,GWGR 携带者与其他携带者之间在人口统计学特征、CD4+细胞计数、艾滋病进展或死亡率方面无显著差异。然而,携带 GWGR 特征的女性从首次 HIV 阳性检测到首次艾滋病定义性事件的平均间隔时间延长了两倍以上(p=0.0231)。我们强调 cART 对 HIV/AIDS 治疗的积极影响,包括病毒抑制、CD4+细胞保存和免疫功能维持。尽管在 cART 期间未发现显著差异,但在诊断和首次艾滋病定义性事件之间仍观察到反映依从性挑战的残留结局。之前描述的结果,突出了携带 GPGR 基序的个体与携带巴西 GWGR 基序的个体之间的统计学显著差异,可能与 cART 前感染的自然进展直接相关。目前,这些物理化学方面可能不再具有相同的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c065/11251515/f31e3aaf050e/1678-9946-rimtsp-66-S1678-9946202466038-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c065/11251515/d0ee96a11a17/1678-9946-rimtsp-66-S1678-9946202466038-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c065/11251515/f31e3aaf050e/1678-9946-rimtsp-66-S1678-9946202466038-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c065/11251515/d0ee96a11a17/1678-9946-rimtsp-66-S1678-9946202466038-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c065/11251515/f31e3aaf050e/1678-9946-rimtsp-66-S1678-9946202466038-gf02.jpg

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