Interferon-α and 3′-azido-3′-deoxythymidine are highly synergistic in mice and prevent viremia after acute retrovirus exposure Journal Article
| Authors: | Ruprecht, R. M.; Chou, T. C.; Chipty, F.; Sosa, M. G.; Mullaney, S.; O'Brien, L.; Rosas, D. |
| Article Title: | Interferon-α and 3′-azido-3′-deoxythymidine are highly synergistic in mice and prevent viremia after acute retrovirus exposure |
| Abstract: | This study was undertaken to calculate the in vivo drug interactions between recombinant human interferon-αA/D (rHuIFN-αA/D) and 3′-azido-3′-deoxythymidine (AZT) in a quantitative model for retroviral viremia. When given as single agents, both AZT and rHuIFN-αA/D suppressed virus-induced splenomegaly in a dose-dependent fashion in mice inoculated with Rauscher murine leukemia virus (RLV). However, suppressive doses of single-agent AZT caused anemia after 20 days of therapy. Combining rHuIFN-αA/D with AZT allowed drastic dose reductions for each agent while maintaining ≥93% inhibition of splenomegaly. No clinically significant toxicity was seen. Computer analysis with the isobologram technique and combination index method showed that these combination regimens were highly synergistic. A 20-day course of AZT + rHuIFN-αA/D started 4 h after virus exposure was protective against RLV viremia and disease. After cessation of therapy, the animals were resistant to rechallenge with fully infectious RLV. We conclude that prompt initiation of effective combination therapy after retroviral exposure prevented viremia and disease and led to protective immunity. © 1990 Raven Press, New York. |
| Keywords: | nonhuman; alpha interferon; mouse; animal; mice; anemia; cell line; animal experiment; mice, inbred balb c; animalia; drug synergism; drug therapy, combination; prophylaxis; vaccination; murinae; human immunodeficiency virus; virus infection; virus replication; retrovirus; zidovudine; retroviridae infections; viremia; synergy; murine leukemia virus; human immunodeficiency virus vaccine; interferon type i, recombinant; unidentified retrovirus; female; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; combination antiretroviral therapy; azt plus interferon-α; live pathogenic virus; prevention with postexposure chemoprophylaxis; rauscher murine leukemia virus; rauscher leukemia virus; rauscher virus |
| Journal Title: | JAIDS: Journal of Acquired Immune Deficiency Syndromes |
| Volume: | 3 |
| Issue: | 6 |
| ISSN: | 1525-4135 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 1990-06-01 |
| Start Page: | 591 |
| End Page: | 600 |
| Language: | English |
| PUBMED: | 2159992 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
