title: Combinations of reverse transcriptase, protease, and integrase inhibitors can be synergistic in vitro against drug-sensitive and RT inhibitor-resistant molecular clones of HIV-1.
abstract: Combinations of anti-HIV agents including one or two reverse transcriptase inhibitors with a protease inhibitor are potent and effective. However, toxicities, costs and the emergence of drug-resistant organisms have compromised their long-term efficacy in people. A next, likely, target for anti-HIV therapy is HIV-1 integrase. Viral integration, catalyzed by integrase, is absolutely required for HIV replication. L-chicoric acid is a potent and selective inhibitor of HIV-1 integrase that also inhibits HIV-1 replication in cell culture. As a first step in understanding the potential role for integrase inhibitors in clinical medicine, the activities of L-chicoric acid alone and in combination with 2', 3'-dideoxycytidine, zidovudine, and a protease inhibitor, nelfinavir, were tested in vitro against molecular clones of HIV-1 resistant to reverse transcriptase inhibitors. L-chicoric acid was equally effective against a wild-type clone of HIV-1, HIV(NL4-3), or against HIV-1 resistant to either zidovudine or dideoxycytidine. L-chicoric acid was largely synergistic with zidovudine and synergistic with both dideoxycytidine and nelfinavir.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine 92697-4800, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Beale
authors.forename: W E
authors.initials: WE
authors.lastname: Robinson
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D002109:Caffeic Acids; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013386:Succinates / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D002109:Caffeic Acids; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D013386:Succinates; C100435:chicoric acid