Tyrosine Kinase Inhibition: a New Perspective in the Fight against HIV

Abstract

Purpose of Review: HIV-1 infection is incurable due to the existence of latent reservoirs that persist in the face of cART. In this review, we describe the existence of multiple HIV-1 reservoirs, the mechanisms that support their persistence, and the potential use of tyrosine kinase inhibitors (TKIs) to block several pathogenic processes secondary to HIV-1 infection. Recent Findings: Dasatinib interferes in vitro with HIV-1 persistence by two independent mechanisms. First, dasatinib blocks infection and potential expansion of the latent reservoir by interfering with the inactivating phosphorylation of SAMHD1. Secondly, dasatinib inhibits the homeostatic proliferation induced by γc-cytokines. Since homeostatic proliferation is thought to be the main mechanism behind the maintenance of the latent reservoir, we propose that blocking this process will gradually reduce the size of the reservoir. Summary: TKIs together with cART will interfere with HIV-1 latent reservoir persistence, favoring the prospect for viral eradication.