HIV entry inhibitors.
The need for new classes of antiretroviral drugs has become apparent because of increasing concern about the long-term toxic effects of existing drugs, the need to combat HIV-1 variants that are resistant to treatment, and the frequency of treatment change in drug-experienced patients. Currently, most regimens are combinations of inhibitors of two viral enzymes--reverse transcriptase and protease. Nevertheless, several steps in the HIV replication cycle are potential targets for intervention. These steps can be divided into entry steps, in which viral envelope glycoproteins and their receptors are involved, and postentry steps, involving viral accessory gene products and the cellular proteins with which they interact. New treatment options target viral entry into the cell. These treatments include the HIV fusion inhibitor enfuvirtide, and new HIV coreceptor antagonists in advanced stages of clinical development or in different stages of preclinical development. Here, we review the development of new HIV entry inhibitors, their performance in clinical trials, and their possible role in anti-HIV therapy.
Esté
José A
JA
Retrovirology Laboratory IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. jaeste@irsicaixa.es
Telenti
Amalio
A
D019380:Anti-HIV Agents / Q000145:classification / Q000627:therapeutic use*; D001596:Benzylamines; D065100:CCR5 Receptor Antagonists; D002986:Clinical Trials as Topic; D000080027:Cyclams; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000502:physiology*; D006571:Heterocyclic Compounds / Q000627:therapeutic use*; D006801:Humans; D010446:Peptide Fragments / Q000627:therapeutic use*; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D001596:Benzylamines; D065100:CCR5 Receptor Antagonists; D000080027:Cyclams; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D006571:Heterocyclic Compounds; D010446:Peptide Fragments; D000077560:Enfuvirtide; C088327:plerixafor