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

ABSTRACT

Introduction: 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.

KEYWORDS:

• HIV/AIDS
• Tyrosine kinase inhibitors
• chronic myeloid leukemia
• immunomodulation
• viral reservoirs
• T-cell activation

Article highlights

• HIV-1 infection is currently incurable due to the formation of viral reservoirs.

• Antiretroviral treatment has transformed HIV-1 infection into a chronic disease that needs life-long treatment.

• CD4+ T cell massive activation during HIV-1 acute infection is mostly responsible for viral spread, the formation of the reservoirs and the destruction of CD4+ T cells.

• Control of CD4+ T cell activation could avoid viral replication and spread and, consequently, the formation of the viral reservoirs.

• Src tyrosine kinases are essential for the activation of CD4+ T cells and their inhibition could avoid the formation of HIV-1 reservoirs.

• Tyrosine kinase inhibitors currently used for treating chronic myeloid leukemia could be potential adjuvants of the antiretroviral treatment during HIV-1 infection.

This box summarizes key points contained in the article.

Acknowledgments

We greatly appreciate the secretarial assistance of Mrs Olga Palao. We also thank Centro Regional de Transfusión Castilla-La Mancha (Toledo, Spain), for providing the buffy coats.

Declaration of interest

J Ambrosioni has received honoraria from speakers’ bureau, educational programs and advisory boards from Gilead, MSD, ViiV healthcare and Janssen pharmaceuticals. JMM has received consulting honoraria and/or research grants from AbbVie, Bristol-Myers Squibb, Cubist, Novartis, Gilead Sciences, and ViiV Healthcare. FC has received honoraria from speakers bureau and advisory boards from Novartis, Bristol-Myers Squibb, Ariad, and Pfizer. J Alcamí and M Coiras received grant support from Bristol-Myers Squibb. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by the Spanish Ministry of Economy and Competitiveness (SAF2013-44677-R, SAF2016-78480-R); the Instituto de Salud Carlos III (INT15/00168, ISCIII-FIS PI16CIII/00034); the Spanish AIDS Research Network RD12/0036/0004, RD16CIII/0002/0001-ISCIII-FEDER and the grant RD12/0036/0004; Bristol-Myers Squibb partially financed our study (grant BMS AI471-041). J Ambrosioni developed this work in the frame of a ‘Juan de la Cierva 2012ʹ postdoctoral program, Spanish Ministry of Economy and Competitiveness, Spain. JMM received a personal intensification research grant INT15/00168 in 2016 from Instituto de Salud Carlos III, Madrid, Spain. The European Regional Development Fund (ERDF) ‘A way to build Europe’ also provided funding.