Synergistic interaction of 2',3'-dideoxycytidine and recombinant interferon-alpha-A on replication of human immunodeficiency virus type 1.
Effective treatment of infections with human immunodeficiency virus type 1 (HIV-1) may require a combination of antiviral drugs that act by different mechanisms. We report that the combination of 2',3'-dideoxycytidine (ddCyd) and recombinant interferon-alpha-A (rIFN-alpha-A) acts synergistically against HIV-1 replication in vitro. Various cell types (peripheral blood leukocytes, a CD4-positive T cell line, and two monocyte-macrophage lines) have been studied. For each set of dose-effect data, the degree of drug interaction was quantitatively assessed with the median-effect principle and the isobologram equation by using a computer analysis. Under various culture conditions using several concentrations of drugs, multiplicities of infectious virus, and assay systems, antiviral synergism was consistently observed against HIV-1 replication without enhanced cell toxicity. Synergism was seen at concentrations as low as 0.02 microM ddCyd plus 4 U of rIFN-alpha-A/mL or 0.01 microM ddCyd plus 8 U of rIFN-alpha-A/mL, whereas 10-fold higher concentrations were usually required to achieve similar effects with single drugs.
Vogt
M W
MW
Infectious Disease Unit, Massachusetts General Hospital, Boston 02114.
Durno
A G
AG
Chou
T C
TC
Coleman
L A
LA
Paradis
T J
TJ
Schooley
R T
RT
Kaplan
J C
JC
Hirsch
M S
MS
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D006678:HIV / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007962:Leukocytes / Q000382:microbiology; D011994:Recombinant Proteins; D013936:Thymidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*; D016047:Zalcitabine; D015215:Zidovudine
D000998:Antiviral Agents; D007370:Interferon Type I; D011994:Recombinant Proteins; D003841:Deoxycytidine; D015215:Zidovudine; D016047:Zalcitabine; D013936:Thymidine