Human immunodeficiency virus type 1 (HIV-1) inhibitory interactions between protease inhibitor Ro 31-8959 and zidovudine, 2',3'-dideoxycytidine, or recombinant interferon-alpha A against zidovudine-sensitive or -resistant HIV-1 in vitro.
Protease inhibitor Ro 31-8959, a compound that interrupts human immunodeficiency virus (HIV)-specific formation of infectious virions, was evaluated in two-drug combined regimens with zidovudine, 2',3'-dideoxycytidine (ddC), or recombinant interferon-alpha A (rIFN-alpha A) against HIV-1 replication in vitro. By using peripheral blood mononuclear cells infected with HIV-1, drug interactions were evaluated by the median-effect principle and the isobologram technique. A zidovudine-sensitive and -resistant HIV-1 isolate pair was studied. Additive to synergistic anti-HIV-1 interactions were seen with 7.5-30 nM Ro 31-8959 and 0.005-0.02 microM zidovudine (for the zidovudine-sensitive HIV-1 isolate), 0.25-1.0 microM zidovudine (for the zidovudine-resistant HIV-1 isolate), 0.025-0.1 microM ddC, and 8-32 units/mL rIFN-alpha A, without additive toxicity. Phase I/II clinical trials of Ro 31-8959 for therapy of HIV-1 infection are in progress. If results are favorable, combined regimens including Ro 31-8959 deserve consideration for future clinical trials.
Johnson
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VA
Infectious Disease Unit, Massachusetts General Hospital, Boston.
Merrill
D P
DP
Chou
T C
TC
Hirsch
M S
MS
D002478:Cells, Cultured; D004347:Drug Interactions; D004352:Drug Resistance, Microbial; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D009000:Monocytes; D011804:Quinolines / Q000494:pharmacology*; D011994:Recombinant Proteins; D019258:Saquinavir; D014779:Virus Replication / Q000187:drug effects*; D016047:Zalcitabine / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*
D017320:HIV Protease Inhibitors; D007370:Interferon Type I; D007546:Isoquinolines; D011804:Quinolines; D011994:Recombinant Proteins; D015215:Zidovudine; D016047:Zalcitabine; D019258:Saquinavir