title: New developments in anti-HIV chemotherapy.
abstract: Virtually all the compounds that are currently used, or under advanced clinical trial, for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): i.e. zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, tenofovir (PMPA) disoproxil fumarate; (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs): i.e. nevirapine, delavirdine, efavirenz, emivirine; and (iii) protease inhibitors (PIs): i.e. saquinavir, ritonavir, indinavir, nelfinavir and amprenavir. In addition, various other events in the HIV replicative cycle are potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120; (ii) viral entry, through blockade of the viral coreceptors CXCR4 and CCR5; (iii) virus-cell fusion; (iv) viral assembly and disassembly; (v) proviral DNA integration; (vi) viral mRNA transcription. Also, new NRTIs, NNRTIs and PIs have been developed that possess respectively improved metabolic characteristics, or increased activity against NNRTI-resistant HIV strains or, as in the case of PIs, a different, non-peptidic scaffold. Given the multitude of molecular targets with which anti-HIV agents can interact, one should be cautious in extrapolating from cell-free enzymatic assays to the mode of action of these agents in intact cells.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium. erik.declercq@rega.kuleuven.ac.be
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D019426:Integrases / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D016335:Zinc Fingers
chemical_list: D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D017320:HIV Protease Inhibitors; D019718:Receptors, CXCR4; D018894:Reverse Transcriptase Inhibitors; D019426:Integrases