Multiple interventions to eliminate HIV reservoirs among antiretroviral treated individuals in order to obtain sustained HIV remission without antiretrovirals

• Grant number: 20/10396-2
• Support Opportunities: Research Projects - Thematic Grants
• Start date: April 01, 2021
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ricardo Sobhie Diaz
• Grantee: Ricardo Sobhie Diaz
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Alfredo Mendrone Junior ; ANDREA SAVARINO ; Cesar de Almeida Neto ; Iart Luca Shytaj ; Luiz Mário Ramos Janini ; Maria Aparecida Juliano ; Maria Cecilia Araripe Sucupira ; Shirley Cavalcante Vasconcelos
• Associated scholarship(s): 24/16200-3 - Information Technology in the research area: Implementation of patient registry - a strategic management model for the service in scientific research., BP.TT; 23/14729-4 - Plasma Metabolomic analysis of HIV-1 infected individuals to identify specific disease biomarkers and understanding the metabolic pathways of the infection to guide in treatment intervention., BP.TT; 23/07355-0 - MODULATION OF SIGNALING PATHWAYS MEDIATED BY CCR5 EXPRESSION IN INFECTED HIV1 patients RECEIVING DIFFERENT INTERVENTIONS AIMing THE STERILIZING CURE OF CHRONIC HIV-1 INFECTION., BP.TT; + associated scholarships 22/05655-4 - MODULATION OF THE mTOR SIGNALING PATHWAY MEDIATED BY CELL REDOX ENVIRONMENT CHANGES IN HIV-1-INFECTED INDIVIDUALS RECEIVING DIFFERENT INTERVENTIONS THAT AIM FOR STERILIZING CURE OF CHRONIC HIV-1 INFECTION, BP.IC; 21/11341-0 - Evaluation of the epigenetic alterations among HIV-1 infected individuals receiving multiple interventions aiming at chronic infection remission without antiretrovirals, BP.PD; 21/11376-8 - Statistical and bioinformatics techniques relevant to the development of strategies for the elimination of HIV-1 viral reservoirs, BP.PD - associated scholarships

Abstract

A modern and urgent challenge in fighting HIV infection is to achieve sustained HIV remission without the use of antiretrovirals. Our preliminary data indicate that the use of combined strategies to mitigate the HIV proviral reservoir size among individuals with suppressive antiretroviral treatment achieved unprecedented results in the reduction of HIV DNA present in these cells and in the reduction of CD4 + and CD8 + T cell activation. . Combined interventions include intensified antiretroviral treatment to mitigate residual HIV replication, use of a histone deacetylase inhibitor to interrupt viral latency, use of an anti-proliferative medication to reduce long-lived T cells that harbor HIV and a personalized dendritic cell therapy vaccine to eliminate cells with latent HIV infection or cells present in viral sanctuaries. Due to the good results obtained in the exploratory stage of the project, we propose to expand it by recruiting a larger number of patient to confirm the previously obtained results and to generate new insights related to the mechanisms involved in viral latency, latency disruption and the effects of analytical treatment interruption of antiretrovirals among patients undergoing all above mentioned interventions. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PENA, NATHALIA MANTOVANI; SANTANA, LUIZ CLAUDIO; HUNTER, JAMES R.; BLUM, VINICIUS FONTANESI; VERGARA, TANIA; GOUVEA, CELSO; LEAL, ELCIO; BELLEI, NANCY; SCHECHTER, MAURO; DIAZ, RICARDO SOBHIE. T cell-mediated Immune response and correlates of inflammation and their relationship with COVID-19 clinical severity: not an intuitive guess. BMC INFECTIOUS DISEASES, v. 24, n. 1, p. 11-pg., 2024-06-20. (20/10396-2)

MANTOVANI, NATHALIA; DEFELICIBUS, ALEXANDRE; DA SILVA, ISRAEL TOJAL; CICERO, MAIRA FERREIRA; SANTANA, LUIZ CLAUDIO; ARNOLD, RAFAEL; DE CASTRO, DANIELA FUNAYAMA; SANZ DURO, RODRIGO LOPES; NISHIYAMA-JR, MILTON YUTAKA; MEIRELLES JUNQUEIRA-DE-AZEVEDO, INACIO LOIOLA; et al. Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response. SCIENTIFIC REPORTS, v. 11, n. 1, NOV 26 2021. (13/06584-4, 20/10396-2, 13/02652-5, 14/09623-3)