In vivo additive antiretroviral effect of combined zidovudine and foscarnet therapy for human immunodeficiency virus infection (ACTG Protocol 053)

Abstract

Zidovudine and foscarnet each have antiretroviral activity against human immunodeficiency virus (HIV) and, when combined in vitro, inhibit HIV replication in an additive or synergistic fashion. To determine if an in vivo additive or synergistic antiretroviral effect might result from combined therapy, six symptomatic HIV-infected patients were studied who had persistently quantifiable serum HIV p24 antigen despite 9-27 weeks of full-dose oral zidovudine therapy (1200 mg/day). These patients were given intravenous foscarnet (30 mg/kg every 8h) for 2 weeks with continued oral zidovudine for 14 days, followed by zidovudine alone for 6 months. Serum p24 antigen concentrations decreased in all six patients during the period of combined therapy by a mean 53% (P = .005). Subsequently, serum p24 antigen levels rose to the baseline value in four patients after 4-14 weeks. As predicted from in vitro studies, combined treatment with zidovudine and foscarnet resulted in an additive in vivo effect, but the effect was transient.