In vitro inhibition of human immunodeficiency virus type 1 by a combination of delavirdine (U-90152) with protease inhibitor U-75875 or interferon-alpha.
Delavirdine (bisheteroarylpiperazine, U-90152), a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1), was evaluated in a two-drug combination with recombinant human interferon-alpha (IFN-alpha) or the peptidomimetic protease inhibitor U-75875 against HIV-1 replication in vitro. Viral growth was assayed in a CD4+ T cell line (H9) infected with HIVIIIB and in human peripheral blood mononuclear cells infected with the clinical isolate HIVJRCSF. Drug synergy, estimated by the combination index method and the method of Pritchard and Shipman, was observed when delavirdine was combined with U-75875 or IFN-alpha over a range of drug concentrations (delavirdine: 0.001, 0.003, 0.01, 0.03 microM; U-75875: 0.01, 0.03, 0.1, 0.3, 1.0 microM; IFN-alpha: 2, 6, 17, and 50 or 10, 30, 100, and 300 IU/mL). The combinations showed no detectable drug antagonism or cytotoxicity. These in vitro synergy data support the potential use of delavirdine with either a protease inhibitor or IFN-alpha in patients with AIDS.
Pagano
P J
PJ
Upjohn Laboratories, Kalamazoo, Michigan 49001.
Chong
K T
KT
D000998:Antiviral Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020008:Delavirdine; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007370:Interferon Type I / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D007211:Indoles; D007370:Interferon Type I; D009842:Oligopeptides; D010879:Piperazines; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; C065978:U 75875; D020008:Delavirdine; D054303:HIV Reverse Transcriptase