Three-drug synergistic inhibition of HIV-1 replication in vitro by 3'-fluoro-3'-deoxythymidine, recombinant soluble CD4, and recombinant interferon-alpha.
3'-Fluoro-3'deoxythymidine (FLT), recombinant soluble CD4 (CD4), and recombinant interferon-alpha (IFN alpha) were evaluated in two- and three-drug regimens against HIV-1 replication in vitro. Peripheral blood mononuclear cells were studied using p24 antigen production as the virologic endpoints. FLT showed 2.5-fold higher efficacy and a similar selectivity index to zidovudine. Drug interactions were evaluated by the median effect principle and the isobologram technique. FLT, CD4, and interferon alpha at noncytotoxic concentrations inhibited HIV-1 synergistically in two- and three-drug combinations with a combination index smaller than one and dose reduction index greater than one. The three-drug regimen provided greater virus suppression than the two-drug regimen. These results suggest that FLT is an alternative agent to AZT for the treatment of HIV infection either as a single agent or in combination with CD4 and/or interferon-alpha.
Pan
X Z
XZ
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
Qiu
Z D
ZD
Baron
P A
PA
Gold
J W
JW
Polsky
B
B
Chou
T C
TC
Armstrong
D
D
D000998:Antiviral Agents / Q000494:pharmacology*; D015704:CD4 Antigens; D002478:Cells, Cultured; D015224:Dideoxynucleosides / Q000494:pharmacology*; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000502:physiology; D012995:Solubility; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015704:CD4 Antigens; D015224:Dideoxynucleosides; D016898:Interferon-alpha; D011994:Recombinant Proteins; C002854:alovudine