Three-drug synergistic inhibition of HIV-1 replication in vitro by zidovudine, recombinant soluble CD4, and recombinant interferon-alpha A Journal Article


Authors: Johnson, V. A.; Barlow, M. A.; Merrill, D. P.; Chou, T. C.; Hirsch, M. S.
Article Title: Three-drug synergistic inhibition of HIV-1 replication in vitro by zidovudine, recombinant soluble CD4, and recombinant interferon-alpha A
Abstract: Optimal management of human immunodeficiency virus type 1 (HIV-l) infections may require combinations of agents that attack different targets in the viral replicative cycle. Zidovudine (AZT), recombinant soluble CD4 (rsCD4), and recombinant interferon-alpha A (rIFN-αA) were evaluated in 2- and 3-drug regimens against HIV-l replication in vitro. Peripheral blood mononuclear cells and a CD4+T cell line (H9) were studied using multiple HIV-l replicative end points. Drug interactions were evaluated by the median-effect principle and the isobologram technique. AZT, rsCD4, and rIFN-αA inhibited HIV-l synergistically in 2- and 3-drug combinations. The 3-drug regimen provided more complete virus suppression than the 2-drug regimens. In H9 cells, single-drug regimens lost effectiveness at 10-14 days and 2-drug regimens lost effectiveness at 14-18 days. In contrast, the 3-drug regimen showed nearly complete suppression over 28 days in culture without toxicity. Clinical trials of these 3 drugs in combination should be considered. © 1990, University of Chicago. All rights reserved.
Keywords: nonhuman; human immunodeficiency virus infection; t-lymphocytes; cells, cultured; cell line; in vitro study; drug synergism; leukocytes, mononuclear; cell culture; recombinant proteins; cd4 antigen; virus replication; enzyme-linked immunosorbent assay; alpha2a interferon; antigens, cd4; human immunodeficiency virus 1; hiv-1; zidovudine; recombinant alpha2a interferon; interferon type i, recombinant; human; priority journal; article; support, u.s. gov't, p.h.s.; alpha interferon a
Journal Title: Journal of Infectious Diseases
Volume: 161
Issue: 6
ISSN: 0022-1899
Publisher: Oxford University Press  
Date Published: 1990-06-01
Start Page: 1059
End Page: 1067
Language: English
DOI: 10.1093/infdis/161.6.1059
PUBMED: 2345291
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 27 January 2020 -- Source: Scopus
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  1. Ting-Chao Chou
    319 Chou