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酪氨酸激酶抑制剂:在HIV-1感染中的潜在用途及安全性考量

Tyrosine kinase inhibitors: potential use and safety considerations in HIV-1 infection.

作者信息

Coiras Mayte, Ambrosioni Juan, Cervantes Francisco, Miró José M, Alcamí José

机构信息

a AIDS Immunopathology Unit , National Center of Microbiology, Instituto de Salud Carlos III , Madrid , Spain.

b Infectious Diseases Service , AIDS Research Group, Institut d´Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) , Barcelona , Spain.

出版信息

Expert Opin Drug Saf. 2017 May;16(5):547-559. doi: 10.1080/14740338.2017.1313224. Epub 2017 Apr 26.

DOI:10.1080/14740338.2017.1313224
PMID:28387147
Abstract

Infection caused by HIV-1 is nowadays a chronic disease due to a highly efficient antiretroviral treatment that is nevertheless, unable to eliminate the virus from the organism. New strategies are necessary in order to impede the formation of the viral reservoirs, responsible for the failure of the antiretroviral treatment to cure the infection. Areas covered: The purpose of this review is to discuss the possibility of using tyrosine kinase inhibitors (TKIs) for the treatment of HIV-1 infection. These inhibitors are successfully used in patients with distinct cancers such as chronic myeloid leukemia. The most relevant papers have been selected and commented. Expert opinion: The family of TKIs are directed against the activation of tyrosine kinases from the Src family. Some of these kinases are essential for the activation of CD4 + T cells, the major target of HIV-1. During acute or primary infection the CD4 + T cells are massively activated, which is mostly responsible for the generation of the reservoirs, the spread of the infection and the destruction of activated CD4 + T cells, infected or not. Consequently, we discuss the possibility of using TKIs as adjuvant of the antiretroviral treatment against HIV-1 infection mostly, but not exclusively, during the acute/recent phase.

摘要

由于高效抗逆转录病毒治疗,如今HIV-1感染已成为一种慢性病,不过这种治疗无法从机体中清除病毒。为了阻止病毒储存库的形成(病毒储存库是抗逆转录病毒治疗无法治愈感染的原因),需要新的策略。涵盖领域:本综述的目的是讨论使用酪氨酸激酶抑制剂(TKIs)治疗HIV-1感染的可能性。这些抑制剂已成功用于治疗慢性髓性白血病等多种癌症患者。已挑选并评论了最相关的论文。专家观点:TKIs家族针对Src家族酪氨酸激酶的激活。其中一些激酶对于HIV-1的主要靶细胞CD4 + T细胞的激活至关重要。在急性或初次感染期间,CD4 + T细胞会大量激活,这主要导致了病毒储存库的产生、感染的传播以及已激活的CD4 + T细胞(无论是否被感染)的破坏。因此,我们主要讨论在急性/近期阶段(但不仅限于此阶段)使用TKIs作为抗逆转录病毒治疗HIV-1感染辅助药物的可能性。

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