title: Potential use of rapamycin in HIV infection.
abstract: The strong need for the development of alternative anti-HIV agents is primarily due to the emergence of strain-resistant viruses, the need for sustained adherence to complex treatment regimens and the toxicity of currently used antiviral drugs. This review analyzes proof of concept studies indicating that the immunomodulatory drug rapamycin (RAPA) possesses anti-HIV properties both in vitro and in vivo that qualifies it as a potential new anti-HIV drug. It represents a literature review of published studies that evaluated the in vitro and in vivo activity of RAPA in HIV. RAPA represses HIV-1 replication in vitro through different mechanisms including, but not limited, to down regulation of CCR5. In addition RAPA synergistically enhances the anti-HIV activity of entry inhibitors such as vicriviroc, aplaviroc and enfuvirtide in vitro. RAPA also inhibits HIV-1 infection in human peripheral blood leucocytes-SCID reconstituted mice. In addition, a prospective nonrandomized trial of HIV patient series receiving RAPA monotherapy after liver transplantation indicated significantly better control of HIV and hepatitis C virus (HCV) replication among patients taking RAPA monotherapy. Taken together, the evidence presented in this review suggests that RAPA may be a useful drug that should be evaluated for the prevention and treatment of HIV-1 infection.
authors.affiliation: Department of Biomedical Sciences, University of Catania, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Donia
authors.forename: James A
authors.initials: JA
authors.lastname: McCubrey
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D051379:Mice; D020123:Sirolimus / Q000627:therapeutic use*; D057170:Translational Research, Biomedical / Q000379:methods; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D020123:Sirolimus