title: Metabolic stress in infected cells may represent a therapeutic target for human immunodeficiency virus infection.
abstract: Worldwide, there are thousands of new cases of human immunodeficiency virus-1 (HIV-1) infection per day. The effectiveness of current combination antiretroviral therapy (ART) is relative; to prioritize finding vaccines and/or cure-oriented initiatives should be reinforced because there is little room, if any, for procrastination. Basic and clinical findings on HIV-1 reservoirs suggest that disruption of virus latency is feasible. Because the goal is curing HIV-1 infection, we should be aware that the challenge is to eradicate the viruses of every single infected cell and consequently acting upon virus latency is necessary but not sufficient. The large majority of the virus reservoir, CD4(+) T lymphocytes, is readily accessible but other minor reservoirs, where ART does not diffuse, require innovative strategies. The situation closely resembles that currently faced in the treatment of cancer. Exploiting the fact that histone deacetylase inhibitors, mainly vorinostat, may disrupt the latency of HIV-1, we propose to supplement this effect with a programmed interference in the metabolic stress of infected cells. Metformin and chloroquine are cheap and accessible modulators of pro-survival mechanisms to which viruses are constantly confronted to generate alternative energy sources and maximize virus production. Metformin restrains the use of the usurped cellular biosynthetic machinery by viral genes and chloroquine contributes to death of infected cells. We suggest that the combination of vorinostat, chloroquine and metformin should be combined with ART to pursue viral eradication in infected cells.
authors: Unitat de Recerca Biomèdica (URB), IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors: Carlos
authors: C
authors: Alonso-Villaverde
authors: Javier A
authors: JA
authors: Menéndez
authors: Jorge
authors: J
authors: Joven
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002738:Chloroquine / Q000627:therapeutic use; D042822:Genomic Instability; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008687:Metformin / Q000627:therapeutic use; D008962:Models, Theoretical; D013312:Stress, Physiological
chemical_list: D019380:Anti-HIV Agents; D002738:Chloroquine; D008687:Metformin