Three-Drug Synergistic Inhibition of HIV-1 Replication In Vitro by 3′-Fluoro-3′-Deoxythymidine, Recombinant Soluble CD4, and Recombinant Interferon-Alpha

Xiao Zhang Pan, Zhong da Qiu, Penny A. Baron, Jonathan W.m. Gold, Bruce Polsky, Ting Chao Chou, Donald Armstrong

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9 Scopus citations

Abstract

3′-Fluoro-3′deoxythymidine (FLT), recombinant soluble CD4 (CD4), and recombinant interferon-alpha (IFNα) 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.

Original languageEnglish
Pages (from-to)589-595
Number of pages7
JournalAIDS Research and Human Retroviruses
Volume8
Issue number5
DOIs
StatePublished - May 1992
Externally publishedYes

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