| Synergistic drug interactions of an HIV-1 protease inhibitor with AZT in different in vitro models of HIV-1 infection. | |
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MedLine Citation:
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PMID: 7692816 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Synthetic peptide mimetic inhibitors of HIV-1 protease effectively block spread of infectious virus in acutely infected T-cells. These compounds also inhibit production of infectious virions from chronically infected T-cell lines. In order to determine the potential for drug interaction effects on antiviral activity, an HIV-1 protease inhibitor (SK&F 108922) and AZT were studied in three different in vitro models of HIV-1 infection of T-cell lines, specifically, (1) acutely infected cells infected at low multiplicity, (2) HIV-1 chronically-infected cells and (3) co-cultivations of chronically infected with non-infected cells. Upon co-treatment, these compounds demonstrated synergy in Molt4 or H9 cells acutely infected with HIV-1 strain IIIB. Either compound alone was a potent inhibitor of HIV-1 in co-cultivations of uninfected and chronically infected cells. In combination treatments of co-cultures, SK&F 108922 demonstrated strong synergy with AZT. Treatment of H9/IIIB chronically infected cells demonstrated no inhibitory effect by AZT treatment (EC50 = > 100 microM) whereas SK&F 108922 was inhibitory (EC50 = 3 microM). Upon co-treatment of H9/IIIB chronically infected cultures with both compounds, the antiviral activity was similar to that of the protease inhibitor alone suggesting no drug interaction. In the co-cultivation experiments, AZT's antiviral effect was most likely due to blocking spread of acute infection to uninfected cells in the culture. No antagonistic effects were observed with AZT and SK&F 108922 co-treatments. These results clearly demonstrate that an HIV-1 protease inhibitor can exert a potent antiviral effect on chronically infected T-cells in contrast to AZT and is capable of potent synergy with AZT in acute and co-culture in vitro infection models. |
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Authors:
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D M Lambert; H Bartus; A V Fernandez; C Bratby-Anders; J J Leary; G B Dreyer; B W Metcalf; S R Petteway |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Antiviral research Volume: 21 ISSN: 0166-3542 ISO Abbreviation: Antiviral Res. Publication Date: 1993 Aug |
Date Detail:
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Created Date: 1993-11-12 Completed Date: 1993-11-12 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8109699 Medline TA: Antiviral Res Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 327-42 Citation Subset: IM; X |
Affiliation:
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Department of Molecular Virology and Host Defense, SmithKline Beecham Research Laboratories, King of Prussia, PA 19406. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acquired Immunodeficiency Syndrome
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drug therapy* Amino Acid Sequence Cell Line Chronic Disease Drug Synergism HIV Protease Inhibitors / pharmacology* HIV Reverse Transcriptase HIV-1 / drug effects, enzymology Humans Models, Biological Molecular Sequence Data Oligopeptides / pharmacology* RNA-Directed DNA Polymerase / biosynthesis, metabolism Virus Replication / drug effects Zidovudine / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/HIV Protease Inhibitors; 0/Oligopeptides; 146794-68-5/SK&F 108922; 30516-87-1/Zidovudine; EC 2.7.7.49/HIV Reverse Transcriptase; EC 2.7.7.49/RNA-Directed DNA Polymerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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