Evaluation of the combination effect of different antiviral compounds against HIV in vitro.
3'-azido-3'deoxythymidine (AZT), a clinically used anti-HIV compound, was evaluated for antiviral effect on HIV infection in combination with other antiviral compounds in vitro. Interactions were evaluated by the median-effect principle and the isobologram technique. Synergistic effect was obtained by combining many evaluated antiviral agents with AZT. We observed a difference in the degree of synergism depending on the evaluated compound; the results indicate that compounds with the same target in the viral replicative cycle (ddI: 2',3'-dideoxyinosine, didanosine; d4T: 2',3'-dideoxy-2',3'-didehydrothymidine stavodine; TIBO: tetrahydro-imidazole-benzodiazepin) had a synergistic effect at all concentrations, agents that disturb the infectivity of virus (CAS: Castanospermine; AME: Amphotericin B Methyl Ester) exerted a strong synergistic effect at low concentrations, and finally compounds interfering with the adhesion/penetration process of virus (ConA: Concanavalin A; DS: dextran sulfate) were most potent with AZT when used in rather high concentrations. At this moment in the HIV epidemic, these observations suggest that combinations of antiviral compounds should be evaluated in clinical trials, with the major emphasis on nucleoside analogues and compounds influencing the infectivity of the virus.
Sørensen
A M
AM
Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Denmark.
Nielsen
C
C
Mathiesen
L R
LR
Nielsen
J O
JO
Hansen
J E
JE
D000998:Antiviral Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D016049:Didanosine / Q000494:pharmacology; D015224:Dideoxynucleosides / Q000494:pharmacology; D004338:Drug Combinations; D004341:Drug Evaluation; D004357:Drug Synergism; D006678:HIV / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D015215:Zidovudine / Q000494:pharmacology
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D004338:Drug Combinations; D007093:Imidazoles; D018894:Reverse Transcriptase Inhibitors; D001569:Benzodiazepines; D015215:Zidovudine; C067413:R-82913; D018119:Stavudine; D016049:Didanosine