HIV-chemotherapy and -prophylaxis: new drugs, leads and approaches.
In recent years, significant progress has been made towards the chemotherapy (and prophylaxis) of HIV infections. This progress is situated at three different levels. (i) New anti-HIV drugs have been approved for clinical use and have entered the market: the virus entry inhibitor enfuvirtide (Fuzeon), the nucleoside reverse transcriptase inhibitor (NRTI) emtricitabine (Emtriva), the nucleotide reverse transcriptase inhibitor (NtRTI) tenofovir disoproxil fumarate (Viread trade mark ) and the HIV protease inhibitor (PI) atazanavir (Reyataz trade mark ). (ii) Other compounds have proceeded through preclinical and/or clinical development: CXCR4 antagonists (i.e. AMD070), CCR5 antagonists (i.e. SCH-C), NRTIs (such as amdoxovir), NNRTIs (such as etravirine), integrase inhibitors (such as S-1360) and PIs (such as tipranavir). (iii) Yet other compounds, acting by novel mechanisms, have recently been identified as anti-HIV agents that seem worthy of further (pre)clinical development: cell receptor CD4 down-modulators (i.e. cyclotriazadisulfonamides), viral envelope gp120-binding agents such as plant lectins and glycopeptide antibiotics, HIV integrase inhibitors such as the pyranodipyrimidine V-165, and two new classes of compounds (i.e. N-aminoimidazoles and pyridine oxide derivatives) which seem to interfere with a post-integration, transcription transactivation event. Taken together, it is obvious that the approaches for the treatment of HIV infections in recent years have become both more diverse and more efficient.
De Clercq
Erik
E
Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. erik.declercq@rega.kuleuven.ac.be
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015704:CD4 Antigens / Q000187:drug effects / Q000378:metabolism; D018890:Chemoprevention / Q000379:methods; D015536:Down-Regulation; D015699:HIV Envelope Protein gp120 / Q000187:drug effects / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology; D009711:Nucleotides / Q000737:chemistry / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D009705:Nucleosides; D009711:Nucleotides; D019718:Receptors, CXCR4; D018894:Reverse Transcriptase Inhibitors