| Abstract: |
Protease inhibitor Ro 31-8959, a compound that interrupts human immunodeficiency virus (HlV)-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. © 1992 The University of Chicago. |
| Keywords: |
controlled study; human cell; drug potentiation; nonhuman; comparative study; cells, cultured; drug resistance; drug screening; kinetics; mononuclear cell; virus replication; monocytes; proteinase inhibitor; drug interactions; human immunodeficiency virus 1; hiv-1; zidovudine; virus inhibition; quinolines; isoquinolines; saquinavir; drug resistance, microbial; hiv protease inhibitors; interferon type i, recombinant; human; priority journal; article; zalcitabine; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; recombinant alpha interferon a
|
