Evaluation of the epigenetic alterations among HIV-1 infected individuals receiving multiple interventions aiming at chronic infection remission without antiretrovirals

• Grant number: 21/11341-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): November 01, 2021
• Effective date (End): June 30, 2022
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Ricardo Sobhie Diaz
• Grantee: Nathalia Mantovani Pena
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 20/10396-2 - Multiple interventions to eliminate HIV reservoirs among antiretroviral treated individuals in order to obtain sustained HIV remission without antiretrovirals, AP.TEM

Abstract

Despite the ability of the antiretroviral therapy at controlling the HIV-1 replication, there are obstacles that prevent the eradication of the infection. The obstacles that prevent the sterilizing cure of HIV-1 infection are the establishment of viral reservoirs that give rise to residual replication and the viral latency. It is known that viral latency is maintained at least in part by epigenetic modifications that control the reactivation of HIV-1 provirus. For this reason, new strategies have been tested in order to induce the HIV-1 transcription and the consequent elimination of the infected cells by the cytotoxic cells. This project aims to evaluate the methylation and acetylation patterns among HIV-1- infected subjects who receive antiretroviral therapy and are under different strategies aiming at the sterilizing cure. Therefore, the combination of the following strategies will be used: (I) treatment intensification; (II) histone deacetilase inhibitors; (III) drug that changes the cellular phenotype and eliminate the long-term cells; and (IV) dendritic cells vaccination in order to eliminate the chronically infected cells in the sanctuaries. The evaluation of epigenetic patterns among these subjects might be useful to investigate the consequences of these interventions on the epigenetic control and to elucidate the potential impact of the methylation on the HIV-1 persistence in these subjects. (AU)