Human Immunodeficiency Virus Type 1 (HIV-1) Inhibitory Interactions between Protease Inhibitor Ro 31-8959 and Zidovudine, 2',3'-Dideoxycytidine, or Recombinant Interferon- 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-αA (rIFN-αA) 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 µM zidovudine (for the zidovudine-sensitive HIV-1 isolate), 0.25–1.0 µM zidovudine (for the zidovudine-resistant HIV-1 isolate), 0.025–0.1 µM ddC, and 8–32 units/mL, rIFN-αA, 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.