Salvage therapy for zidovudine-intolerant HIV-infected patients with alternating and intermittent regimens of zidovudine and dideoxycytidine. 1990

S A Bozzette, and D D Richman
Division of Infectious Diseases, University of California, San Diego.

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.

UI MeSH Term Description Entries
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D002985 Clinical Protocols Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. Protocols, Clinical,Research Protocols, Clinical,Treatment Protocols,Clinical Protocol,Clinical Research Protocol,Clinical Research Protocols,Protocol, Clinical,Protocol, Clinical Research,Protocols, Clinical Research,Protocols, Treatment,Research Protocol, Clinical,Treatment Protocol
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015215 Zidovudine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. AZT (Antiviral),Azidothymidine,3'-Azido-2',3'-Dideoxythymidine,3'-Azido-3'-deoxythymidine,AZT Antiviral,AZT, Antiviral,BW A509U,BWA-509U,Retrovir,3' Azido 2',3' Dideoxythymidine,3' Azido 3' deoxythymidine,Antiviral AZT,BWA 509U,BWA509U
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D016047 Zalcitabine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. 2',3'-Dideoxycytidine,Dideoxycytidine,ddC (Antiviral),HIVID Roche,Hivid,NSC-606170,2',3' Dideoxycytidine,NSC 606170,NSC606170

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