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. 1994 Feb;38(2):348–352. doi: 10.1128/aac.38.2.348

Combinative interactions of a human immunodeficiency virus (HIV) Tat antagonist with HIV reverse transcriptase inhibitors and an HIV protease inhibitor.

E V Connell 1, M C Hsu 1, D D Richman 1
PMCID: PMC284453  PMID: 7514858

Abstract

Combinations of the human immunodeficiency virus (HIV) Tat protein antagonist Ro 24-7429 with either the HIV protease inhibitor Ro 31-8959 or the HIV reverse transcriptase inhibitors AZT (3'-azido-3'-deoxythymidine), ddC (2',3'-dideoxycytidine), ddI (2',3'-dideoxyinosine), and nevirapine were synergistic or additive in reducing HIV type 1 p24 antigen production in CEM cells or inhibiting HIV type 1-induced syncytium formation in HT4-6C cells.

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Selected References

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  1. Baba M., Ito M., Shigeta S., Tanaka H., Miyasaka T., Ubasawa M., Umezu K., Walker R. T., De Clercq E. Synergistic inhibition of human immunodeficiency virus type 1 replication by 5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil (E-EPU) and azidothymidine in vitro. Antimicrob Agents Chemother. 1991 Jul;35(7):1430–1433. doi: 10.1128/aac.35.7.1430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baba M., Pauwels R., Balzarini J., Herdewijn P., De Clercq E., Desmyter J. Ribavirin antagonizes inhibitory effects of pyrimidine 2',3'-dideoxynucleosides but enhances inhibitory effects of purine 2',3'-dideoxynucleosides on replication of human immunodeficiency virus in vitro. Antimicrob Agents Chemother. 1987 Oct;31(10):1613–1617. doi: 10.1128/aac.31.10.1613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Casareale D., Stevenson M., Sakai K., Volsky D. J. A human T-cell line resistant to cytopathic effects of the human immunodeficiency virus (HIV). Virology. 1987 Jan;156(1):40–49. doi: 10.1016/0042-6822(87)90434-x. [DOI] [PubMed] [Google Scholar]
  4. Chesebro B., Wehrly K. Development of a sensitive quantitative focal assay for human immunodeficiency virus infectivity. J Virol. 1988 Oct;62(10):3779–3788. doi: 10.1128/jvi.62.10.3779-3788.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chou T. C., Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984;22:27–55. doi: 10.1016/0065-2571(84)90007-4. [DOI] [PubMed] [Google Scholar]
  6. Craig J. C., Duncan I. B., Hockley D., Grief C., Roberts N. A., Mills J. S. Antiviral properties of Ro 31-8959, an inhibitor of human immunodeficiency virus (HIV) proteinase. Antiviral Res. 1991 Dec;16(4):295–305. doi: 10.1016/0166-3542(91)90045-s. [DOI] [PubMed] [Google Scholar]
  7. Eron J. J., Jr, Johnson V. A., Merrill D. P., Chou T. C., Hirsch M. S. Synergistic inhibition of replication of human immunodeficiency virus type 1, including that of a zidovudine-resistant isolate, by zidovudine and 2',3'-dideoxycytidine in vitro. Antimicrob Agents Chemother. 1992 Jul;36(7):1559–1562. doi: 10.1128/aac.36.7.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fischl M. A., Richman D. D., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Schooley R. T. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):185–191. doi: 10.1056/NEJM198707233170401. [DOI] [PubMed] [Google Scholar]
  9. Fischl M. A., Richman D. D., Hansen N., Collier A. C., Carey J. T., Para M. F., Hardy W. D., Dolin R., Powderly W. G., Allan J. D. The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection. A double-blind, placebo-controlled trial. The AIDS Clinical Trials Group. Ann Intern Med. 1990 May 15;112(10):727–737. doi: 10.7326/0003-4819-112-10-727. [DOI] [PubMed] [Google Scholar]
  10. Gao W. Y., Shirasaka T., Johns D. G., Broder S., Mitsuya H. Differential phosphorylation of azidothymidine, dideoxycytidine, and dideoxyinosine in resting and activated peripheral blood mononuclear cells. J Clin Invest. 1993 May;91(5):2326–2333. doi: 10.1172/JCI116463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hammer S. M., Gillis J. M. Synergistic activity of granulocyte-macrophage colony-stimulating factor and 3'-azido-3'-deoxythymidine against human immunodeficiency virus in vitro. Antimicrob Agents Chemother. 1987 Jul;31(7):1046–1050. doi: 10.1128/aac.31.7.1046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hartshorn K. L., Vogt M. W., Chou T. C., Blumberg R. S., Byington R., Schooley R. T., Hirsch M. S. Synergistic inhibition of human immunodeficiency virus in vitro by azidothymidine and recombinant alpha A interferon. Antimicrob Agents Chemother. 1987 Feb;31(2):168–172. doi: 10.1128/aac.31.2.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ho D. D., Moudgil T., Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med. 1989 Dec 14;321(24):1621–1625. doi: 10.1056/NEJM198912143212401. [DOI] [PubMed] [Google Scholar]
  14. Hsu M. C., Dhingra U., Earley J. V., Holly M., Keith D., Nalin C. M., Richou A. R., Schutt A. D., Tam S. Y., Potash M. J. Inhibition of type 1 human immunodeficiency virus replication by a tat antagonist to which the virus remains sensitive after prolonged exposure in vitro. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6395–6399. doi: 10.1073/pnas.90.14.6395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hsu M. C., Schutt A. D., Holly M., Slice L. W., Sherman M. I., Richman D. D., Potash M. J., Volsky D. J. Inhibition of HIV replication in acute and chronic infections in vitro by a Tat antagonist. Science. 1991 Dec 20;254(5039):1799–1802. doi: 10.1126/science.1763331. [DOI] [PubMed] [Google Scholar]
  16. Ito M., Baba M., Shigeta S., De Clercq E., Walker R. T., Tanaka H., Miyasaka T. Synergistic inhibition of human immunodeficiency virus type 1 (HIV-1) replication in vitro by 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine (HEPT) and recombinant alpha interferon. Antiviral Res. 1991 May;15(4):323–330. doi: 10.1016/0166-3542(91)90013-h. [DOI] [PubMed] [Google Scholar]
  17. Johnson V. A., Barlow M. A., Merrill D. P., Chou T. C., Hirsch M. S. Three-drug synergistic inhibition of HIV-1 replication in vitro by zidovudine, recombinant soluble CD4, and recombinant interferon-alpha A. J Infect Dis. 1990 Jun;161(6):1059–1067. doi: 10.1093/infdis/161.6.1059. [DOI] [PubMed] [Google Scholar]
  18. Johnson V. A., Merrill D. P., Chou T. C., Hirsch M. S. Human immunodeficiency virus type 1 (HIV-1) inhibitory interactions between protease inhibitor Ro 31-8959 and zidovudine, 2',3'-dideoxycytidine, or recombinant interferon-alpha A against zidovudine-sensitive or -resistant HIV-1 in vitro. J Infect Dis. 1992 Nov;166(5):1143–1146. doi: 10.1093/infdis/166.5.1143. [DOI] [PubMed] [Google Scholar]
  19. Kong X. B., Zhu Q. Y., Ruprecht R. M., Watanabe K. A., Zeidler J. M., Gold J. W., Polsky B., Armstrong D., Chou T. C. Synergistic inhibition of human immunodeficiency virus type 1 replication in vitro by two-drug and three-drug combinations of 3'-azido-3'-deoxythymidine, phosphonoformate, and 2',3'-dideoxythymidine. Antimicrob Agents Chemother. 1991 Oct;35(10):2003–2011. doi: 10.1128/aac.35.10.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Larder B. A., Darby G., Richman D. D. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science. 1989 Mar 31;243(4899):1731–1734. doi: 10.1126/science.2467383. [DOI] [PubMed] [Google Scholar]
  21. Meng T. C., Fischl M. A., Boota A. M., Spector S. A., Bennett D., Bassiakos Y., Lai S. H., Wright B., Richman D. D. Combination therapy with zidovudine and dideoxycytidine in patients with advanced human immunodeficiency virus infection. A phase I/II study. Ann Intern Med. 1992 Jan 1;116(1):13–20. doi: 10.7326/0003-4819-116-1-13. [DOI] [PubMed] [Google Scholar]
  22. Merluzzi V. J., Hargrave K. D., Labadia M., Grozinger K., Skoog M., Wu J. C., Shih C. K., Eckner K., Hattox S., Adams J. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science. 1990 Dec 7;250(4986):1411–1413. doi: 10.1126/science.1701568. [DOI] [PubMed] [Google Scholar]
  23. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  24. Richman D. D., Fischl M. A., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Hirsch M. S. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):192–197. doi: 10.1056/NEJM198707233170402. [DOI] [PubMed] [Google Scholar]
  25. Richman D. D., Grimes J. M., Lagakos S. W. Effect of stage of disease and drug dose on zidovudine susceptibilities of isolates of human immunodeficiency virus. J Acquir Immune Defic Syndr. 1990;3(8):743–746. [PubMed] [Google Scholar]
  26. Richman D., Rosenthal A. S., Skoog M., Eckner R. J., Chou T. C., Sabo J. P., Merluzzi V. J. BI-RG-587 is active against zidovudine-resistant human immunodeficiency virus type 1 and synergistic with zidovudine. Antimicrob Agents Chemother. 1991 Feb;35(2):305–308. doi: 10.1128/aac.35.2.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Roberts N. A., Martin J. A., Kinchington D., Broadhurst A. V., Craig J. C., Duncan I. B., Galpin S. A., Handa B. K., Kay J., Kröhn A. Rational design of peptide-based HIV proteinase inhibitors. Science. 1990 Apr 20;248(4953):358–361. doi: 10.1126/science.2183354. [DOI] [PubMed] [Google Scholar]
  28. Sommadossi J. P. Nucleoside analogs: similarities and differences. Clin Infect Dis. 1993 Feb;16 (Suppl 1):S7–15. doi: 10.1093/clinids/16.supplement_1.s7. [DOI] [PubMed] [Google Scholar]
  29. Vogt M. W., Durno A. G., Chou T. C., Coleman L. A., Paradis T. J., Schooley R. T., Kaplan J. C., Hirsch M. S. Synergistic interaction of 2',3'-dideoxycytidine and recombinant interferon-alpha-A on replication of human immunodeficiency virus type 1. J Infect Dis. 1988 Aug;158(2):378–385. doi: 10.1093/infdis/158.2.378. [DOI] [PubMed] [Google Scholar]
  30. Volberding P. A., Lagakos S. W., Koch M. A., Pettinelli C., Myers M. W., Booth D. K., Balfour H. H., Jr, Reichman R. C., Bartlett J. A., Hirsch M. S. Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. N Engl J Med. 1990 Apr 5;322(14):941–949. doi: 10.1056/NEJM199004053221401. [DOI] [PubMed] [Google Scholar]

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