Therapeutic strategies towards HIV-1 infection in macrophages

• Published in: Antiviral research Vol. 71; no. 2; pp. 293 - 300
• Main Authors: Perno, Carlo Federico, Svicher, Valentina, Schols, Dominique, Pollicita, Michela, Balzarini, Jan, Aquaro, Stefano
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-09-2006; Elsevier
• Subjects: Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiviral agents; Biological and medical sciences; CD4+ lymphocytes; HIV Infections - drug therapy; HIV Infections - virology; HIV-1; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Macrophages; Macrophages - virology; Medical sciences; Pharmacology. Drug treatments; Plant Lectins - chemistry; Plant Lectins - pharmacology; Plant Lectins - therapeutic use; Reverse Transcriptase Inhibitors - therapeutic use; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virus Replication - drug effects; HIV-1; Antiretroviral drugs; CD4+ lymphocytes; Macrophages; Antiretroviral agent; Acyclic nucleoside; HIV-1 virus; Review; Nucleotide analog; Reverse transcriptase inhibitor; T-Lymphocyte; Nucleoside analog; Antiviral; Drug; Immunopathology; Retroviridae; AIDS; Organic phosphonate; Immune deficiency; Lentivirus; Fusion inhibitor; Infection; Virus; Treatment; Viral disease; Human immunodeficiency virus; Protease inhibitor; Macrophage
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2006.05.015

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.