Document 0852
 DOCN  M9480852
 TI    Combination of peptide protease inhibitor and recombinant
       interferon-alpha A synergistically inhibited acute and chronic HIV-1
       infection in vitro.
 DT    9410
 AU    Pagano PJ; Chong KT; Upjohn Laboratories, Kalamazoo, MI.
 SO    Abstr Gen Meet Am Soc Microbiol. 1994;94:485 (abstract no. T-15). Unique
       Identifier : AIDSLINE ASM94/94313093
 AB    Effective treatment of human immunodeficiency virus (HIV) infections may
       require combinations of agents that attack different molecular targets
       in the viral replicative cycle. We investigated the effect of combining
       U-75875, a peptide protease inhibitor containing a non-hydrolyzable
       dihydroxyethylene isostere, with recombinant human interferon-alpha A
       (alpha IFN). HIV-1 infected cells (H9 cells infected with HIV-1 IIIB;
       human peripheral blood mononuclear cells infected with a clinical
       isolate, HIV-1 JRCSF) were cultured in the presence of test compounds
       and drug effects on HIV-1 p24 antigen level in supernatant were measured
       by an ELISA assay. Drug interactions were then evaluated by the
       MacSynergy method of Prichard and Shipman and by the median effect
       principle using the combination index-isobologram technique of Chou and
       Talalay. Over a range of drug concentrations (U-75875 at 0.003, 0.01,
       0.03, and 0.1 microM and alpha IFN at 3, 10, 30, and 100 IU/ml), U-75875
       in combination with alpha IFN synergistically inhibited the replication
       of HIV-1 by both methods of synergy analysis. No significant
       cytotoxicity was observed in the MTT assay at the highest concentrations
       of each agent tested. We conclude that the combination of U-75875 and
       alpha interferon is synergistic against both acute and chronic HIV-1
       replication in vitro.
 DE    Cell Survival/DRUG EFFECTS  Cells, Cultured  Dose-Response Relationship,
       Drug  Drug Synergism  Human  HIV Core Protein p24/ANALYSIS/BIOSYNTHESIS
       HIV Protease Inhibitors/*TOXICITY  HIV-1/*DRUG EFFECTS/PHYSIOLOGY
       Interferon Alfa, Recombinant/*TOXICITY  Monocytes/CYTOLOGY/DRUG EFFECTS
       Oligopeptides/*TOXICITY  Virus Replication/*DRUG EFFECTS  MEETING
       ABSTRACT

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       protected by Copyright Law (Title 17, U.S.Code).