Effect of the Combination of Interferon-a and Stavudine on Friend Virus Infections in (BIO.A X A.By)F1 Mice

The anti-Friend leukemia virus (FL V) effects of interferon-a-A/D (IFN-a) and 2',3'-didehy-dro-2',3'-dideoxythymidine (stavudine) used alone and in combination were examined in Mus dunni cells using a checkerboard-type experiment design. Strong antiviral synergy and a sug-gested cytotoxic synergy were seen. In two experiments to evaluate the effect of combining therapy with IFN-a and stavudine against FLV disease in the hybrid mouse strain (BIO.A X A.By)Fl ' which is a strong producer of cytotoxic T cells, the drug combination resulted in better inhibition of FLV disease than did either drug used alone. Combination therapy inhibited splen-omegaly, splenic virus infectious centers, plasma virus, and the virus-induced increase in hemato-crit to a greater degree than did either drug alone. These data indicate that combination therapy with stavudine and IFN-a is effective in the treatment of murine retrovirus infections and may be of value in the treatment of human AIDS. The thymidine nucleoside analogue 2',3'-didehydro-2',3'-dideoxythymidine (stavudine), an inhibitor of retrovirus re-verse transcriptase, has potent in vitro inhibitory effects on human immunodeficiency virus (HIY) [1-3]. It also inhibit