SALVAGE THERAPY FOR ZIDOVUDINE-INTOLERANT HIV-INFECTED PATIENTS WITH ALTERNATING AND INTERMITTENT REGIMENS OF ZIDOVUDINE AND DIDEOXYCYTIDINE

Zidovudine (AZT) prolongs life in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex but often causes dose-limiting bone marrow suppression in this population. This has prompted a search for salvage therapies for use in persons who cannot tolerate continuous AZT treatment. One approach involves alternating administration of AZT and 2′,3′-dideoxycytidine. 2′,3′-Dideoxycytidine is a potent inhibitor of human immunodeficiency virus in vitro and in vivo. Although it does not cause clinically significant bone marrow suppression, its usefulness at high continuous doses is limited by the occurrence of painful peripheral neuropathy. Because the toxicities of these nucleosides are non-overlapping, intermittent or alternating schedules may limit the toxicity of each agent while extending active antiretroviral therapy in these patients. In an ongoing study, patients have been randomly assigned to weekly intermittent, weekly alternating, and monthly alternating regimens of AZT and 2′,3′-dideoxycytidine. The study will determine the best-tolerated regimen and provide insights into the use of toxic nucleoside analogues in persons with advanced human immunodeficiency virus disease. © 1990.