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实现泛耐药 HIV-1 感染的病毒学控制:病例系列。

Achieving virological control in pan-resistant HIV-1 infection: A case series.

机构信息

Department of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Stamira D'Ancona 20, Milan 20127, Italy.

Department of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Stamira D'Ancona 20, Milan 20127, Italy; Vita-Salute San Raffaele University, Milan, Italy.

出版信息

EBioMedicine. 2022 Mar;77:103906. doi: 10.1016/j.ebiom.2022.103906. Epub 2022 Mar 4.

Abstract

BACKGROUND

HIV-1 pan-resistance refers to a reduced susceptibility to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and integrase strand tranfer inhibitors. Although still anecdotal, its management remains a concern both for affected people living with HIV (PLWH) and for public health.

METHODS

We described genotypic resistance testing (GRT) of three PLWH with a documented poor virological response to previous antiretroviral therapies, who started ibalizumab, an anti-CD4 monoclonal antibody, combined with an optimized background therapy. Both historical and most recent GRT on plasma RNA and peripheral blood mononuclear cell DNA were interpreted according to the Stanford HIVDb version 9.0 (last updated on 22 February, 2021). After the switch to a regimen including the monoclonal antibody, HIV-1 RNA has been quantified biweekly (PCR Cobas® HIV-1 test 6800 Systems, Roche Diagnostics). Follow-up was censored at data freezing (16 January, 2021).

FINDINGS

We report findings from heavily treatment-experienced PLWH with a pan-resistant HIV-1 infection, who achieved virological control once introduced injections of ibalizumab, that is free from cross-resistance with all the antiretroviral drugs available and ensures patient adherence due to a close monitoring attributable to the route of administration, combined with recycled enfuvirtide and an optimized background regimen, selected on the basis of an accurate evaluation of resistance mutations.

INTERPRETATION

In these cases, this new approach has revealed to be a turning point in achieving virological control.

FUNDING

None, this research was supported by internal funding.

摘要

背景

HIV-1 泛耐药是指对核苷类逆转录酶抑制剂、非核苷类逆转录酶抑制剂、蛋白酶抑制剂和整合酶链转移抑制剂的敏感性降低。尽管这仍然是偶发的,但它的管理仍然是受影响的艾滋病毒感染者(PLWH)和公共卫生关注的问题。

方法

我们描述了三名 PLWH 的基因型耐药测试(GRT),他们之前的抗逆转录病毒治疗效果不佳,记录了病毒学反应不良,开始使用ibalizumab,一种抗 CD4 单克隆抗体,与优化的背景治疗相结合。根据斯坦福 HIVDb 版本 9.0(最后更新于 2021 年 2 月 22 日),对血浆 RNA 和外周血单核细胞 DNA 的历史和最近的 GRT 进行了解释。在切换到包括单克隆抗体的方案后,每周两次定量 HIV-1 RNA(PCR Cobas® HIV-1 测试 6800 系统,罗氏诊断)。随访在数据冻结时截止(2021 年 1 月 16 日)。

结果

我们报告了 HIV-1 泛耐药感染的治疗经验丰富的 PLWH 的发现,他们一旦开始注射ibalizumab,就实现了病毒学控制,该药物与所有可用的抗逆转录病毒药物均无交叉耐药性,并由于管理途径的密切监测而确保了患者的依从性,再加上回收的恩夫韦肽和优化的背景方案,该方案是基于对耐药突变的准确评估选择的。

解释

在这些情况下,这种新方法已被证明是实现病毒学控制的一个转折点。

资金

无,这项研究由内部资金支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b0/8897623/426ce2c4344a/gr1.jpg

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