In vitro inhibition of human immunodeficiency virus type 1 by a combination of delavirdine (U-90152) with protease inhibitor U-75875 or interferon-alpha. 1995

P J Pagano, and K T Chong
Upjohn Laboratories, Kalamazoo, Michigan 49001.

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.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007370 Interferon Type I Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA). Interferons Type I,Type I Interferon,Type I Interferons,Interferon, Type I,Interferons, Type I
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell

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