title: Therapeutic strategies towards HIV-1 infection in macrophages.
abstract: It is widely recognized that macrophages (M/M) represent a crucial target of HIV-1 in the body and play a pivotal role in the pathogenic progression of HIV-1 infection. This strongly supports the clinical relevance of therapeutic strategies able to interfere with HIV-1 replication in M/M. In vitro studies showed that nucleoside analogue inhibitors of HIV-1 reverse transcriptase have potent antiviral activity in M/M, although the limited penetration of these compounds in sequestered body compartments and low phosphorylation ability of M/M, suggest that a phosphonate group linked to NRTIs may confer greater anti-HIV-1 activity in M/M. Differently, the antiviral activity of non-nucleoside reverse transcriptase inhibitors in M/M is similar to that found in CD4+ lymphocytes. Interestingly, protease inhibitors, acting at a post-integrational stage of HIV-1 life-cycle are the only drugs active in chronically infected M/M. A careful analysis of the distribution of antiviral drugs, and the assessment of their activity in M/M, represent key factors in the development of therapeutic strategies aimed to the treatment of HIV-1-infected patients. Moreover, testing new and promising antiviral compounds in such cells may provide crucial hints about their efficacy in patients infected by HIV.
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, Via Portuense 292, 00149 Rome, Italy. cf.perno@uniroma2.it
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Valentina
authors.initials: V
authors.lastname: Svicher
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
authors.forename: Michela
authors.initials: M
authors.lastname: Pollicita
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Stefano
authors.initials: S
authors.lastname: Aquaro
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000821:virology*; D037121:Plant Lectins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D037121:Plant Lectins; D018894:Reverse Transcriptase Inhibitors