Abstract |
Protease inhibitor Ro 31-8959, a compound that interrupts human immunodeficiency virus (HIV)-specific formation of infectious virions, was evaluated in two- drug combined regimens with zidovudine, 2',3'-dideoxycytidine (ddC), or recombinant interferon-alpha A (rIFN-alpha A) against HIV-1 replication in vitro. By using peripheral blood mononuclear cells infected with HIV-1, drug interactions were evaluated by the median-effect principle and the isobologram technique. A zidovudine-sensitive and -resistant HIV-1 isolate pair was studied. Additive to synergistic anti-HIV-1 interactions were seen with 7.5-30 nM Ro 31-8959 and 0.005-0.02 microM zidovudine (for the zidovudine-sensitive HIV-1 isolate), 0.25-1.0 microM zidovudine (for the zidovudine-resistant HIV-1 isolate), 0.025-0.1 microM ddC, and 8-32 units/mL rIFN-alpha A, without additive toxicity. Phase I/II clinical trials of Ro 31-8959 for therapy of HIV-1 infection are in progress. If results are favorable, combined regimens including Ro 31-8959 deserve consideration for future clinical trials.
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Authors | V A Johnson, D P Merrill, T C Chou, M S Hirsch |
Journal | The Journal of infectious diseases
(J Infect Dis)
Vol. 166
Issue 5
Pg. 1143-6
(Nov 1992)
ISSN: 0022-1899 [Print] United States |
PMID | 1328402
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- HIV Protease Inhibitors
- Interferon Type I
- Isoquinolines
- Quinolines
- Recombinant Proteins
- Zidovudine
- Zalcitabine
- Saquinavir
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Topics |
- Cells, Cultured
- Drug Interactions
- Drug Resistance, Microbial
- HIV Protease Inhibitors
(pharmacology)
- HIV-1
(drug effects, physiology)
- Humans
- Interferon Type I
(pharmacology)
- Isoquinolines
(pharmacology)
- Kinetics
- Monocytes
- Quinolines
(pharmacology)
- Recombinant Proteins
- Saquinavir
- Virus Replication
(drug effects)
- Zalcitabine
(pharmacology)
- Zidovudine
(pharmacology)
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