Therapeutic strategies towards HIV-1 infection in macrophages

Carlo Federico Perno, Valentina Svicher, Dominique Schols, Michela Pollicita, Jan Balzarini, Stefano Aquaro

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)293-300
Number of pages8
JournalAntiviral Research
Volume71
Issue number2-3 SPEC. ISS.
DOIs
Publication statusPublished - Sep 2006

Keywords

  • Antiretroviral drugs
  • CD4+ lymphocytes
  • HIV-1
  • Macrophages

ASJC Scopus subject areas

  • Virology
  • Pharmacology

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