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监测巴西里约热内卢接受拉替拉韦挽救治疗的 HIV-1 感染患者中耐药突变的出现:一项随访研究。

Monitoring the emergence of resistance mutations in patients infected with HIV-1 under salvage therapy with raltegravir in Rio de Janeiro, Brazil: a follow-up study.

机构信息

Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.

出版信息

J Med Virol. 2012 Dec;84(12):1869-75. doi: 10.1002/jmv.23409.

Abstract

The present study describes a follow-up of a prospective and observational cohort of patients infected with HIV-1 and treated with raltegravir for salvage therapy in Brazil. Two groups of patients were analyzed: switching from T20 to RAL (Group 1, n = 9) and salvage therapy containing RAL (Group 2, n = 10). Blood samples were drawn for CD4(+) T-cell counts and HIV-1 viral load determinations. Protease, reverse transcriptase, and integrase genotyping were performed at baseline and at the time of virologic failure. CD4(+) T-cells increased at 6 and 12 months in both groups; HIV-1 viral load was continuously suppressed for Group 1, and for Group 2 it significantly decreased after starting a RAL-containing regimen. Three out of 10 patients from Group 2 could not suppress HIV-1 viral load. The mutations Q148H + G140S were observed for two patients and for the third patient only mutations to PR/RT inhibitors were detected. The genotypic sensitivity score (GSS) was analyzed for all patients of Group 2 and both patients who developed resistance to raltegravir presented a GSS < 2.0 for the RAL-containing scheme, which could be associated to the lack of effectiveness of the proposed scheme. The present study describes, for the first time in Brazil, the close follow-up of a series of patients using a raltegravir-containing HAART, showing the safety of the enfuvirtide switch to RAL and the effectiveness of a therapeutic regimen with RAL in promoting immune reconstitution and suppressing HIV replication, as well as documenting the occurrence of resistance to integrase inhibitors in the country.

摘要

本研究描述了巴西一项前瞻性、观察性队列研究中 HIV-1 感染者的随访结果,这些患者接受拉替拉韦进行挽救性治疗。分析了两组患者:从 T20 转换为 RAL(第 1 组,n = 9)和挽救性治疗包含 RAL(第 2 组,n = 10)。采集血样用于检测 CD4+T 细胞计数和 HIV-1 病毒载量。在基线和病毒学失败时进行蛋白酶、逆转录酶和整合酶基因分型。两组患者的 CD4+T 细胞计数在 6 和 12 个月时均增加;第 1 组的 HIV-1 病毒载量持续受到抑制,第 2 组在开始包含 RAL 的方案后显著下降。第 2 组的 10 名患者中有 3 名无法抑制 HIV-1 病毒载量。观察到第 2 组的 2 名患者存在 Q148H+G140S 突变,而第 3 名患者仅检测到对 PR/RT 抑制剂的突变。对第 2 组的所有患者和对拉替拉韦产生耐药性的两名患者进行了基因型敏感性评分(GSS)分析,这两名患者对包含 RAL 的方案的 GSS<2.0,这可能与该方案缺乏有效性有关。本研究首次在巴西描述了一系列使用包含拉替拉韦的 HAART 的患者的密切随访情况,表明了从恩夫韦肽转换为拉替拉韦的安全性,以及包含 RAL 的治疗方案在促进免疫重建和抑制 HIV 复制方面的有效性,并记录了该国整合酶抑制剂耐药的发生情况。

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