Two-drug combinations of zidovudine, didanosine, and recombinant interferon-α a inhibit replication of zidovudine-Resistant human immunodeficiency virus type 1 synergistically in vitro

Victoria A. Johnson*, Debra P. Merrill, Joseph A. Videler, Ting Chao Chou, Roy E. Byington, Joseph J. Eron, Richard T. D'Aquila, Martin S. Hirsch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Optimal management of human immunodeficiency virus type 1 (HIV-1) infections may require combinations of anti-HIV-1 agents. Zidovudine (AZT, 3′-azido-3′-deoxythymidine), didanosine (ddI, 2′,3′-dideoxyinosine), and recombinant interferon-α A (rIFN-αA) were evaluated in two-drug regimens against replication of AZT-resistant HIV-1 in vitro. AZT-sensitive and AZT-resistant isolate pairs derived from two individuals before and after extended AZT monotherapy were studied. Drug interactions using peripheral blood mononuclear cells infected with HIV-1 were evaluated mathematically. Synergistic interactions were seen among AZT, ddI, and rIFN-αA in two-drug regimens against AZT-resistant HIV-1 in vitro, even when AZT was included in the treatment regimen. Mixtures of wild-type and mutant reverse transcriptase genes were found in one of the late-AZT therapy isolates, suggesting that the mechanism of synergy of AZT-containing regimens may involve inhibition of AZT-sensitive viruses in the viral pool. These studies suggest that AZT may be useful in drug combination regimens, even when AZT-resistant viruses are isolated in vitro.

Original languageEnglish (US)
Pages (from-to)646-655
Number of pages10
JournalJournal of Infectious Diseases
Volume164
Issue number4
DOIs
StatePublished - Oct 1991

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Two-drug combinations of zidovudine, didanosine, and recombinant interferon-α a inhibit replication of zidovudine-Resistant human immunodeficiency virus type 1 synergistically in vitro'. Together they form a unique fingerprint.

Cite this