ABSTRACT
The murine retrovirus-induced immunodeficiency model, LP-BM5, was used to evaluate the efficacy of intermittent and alternating regimens of zidovudine (azido-2'-3'dideoxythymidine; AZT) and 2'-3' dideoxycytidine (ddC) compared with continuous and concurrent therapy. Intermittent oral AZT therapy was less effective in protecting mice inoculated with LP-BM5 virus than was continuous oral AZT therapy. Continuous oral ddC therapy (80 mg/kg/day) increased survival time an average of 3.5 weeks (P less than .001) compared with that in untreated LP-BM5-infected mice. Alternating weekly AZT and ddC therapy, which increased survival time 3.5 weeks (P less than .001), was more effective than either therapy administered intermittently, although not additive or synergistic. Concurrent AZT and ddC therapy was no more effective than continuous AZT therapy alone in this model, with a 4.4-week increase in survival time (P less than .001).
Subject(s)
HIV Infections/drug therapy , Zalcitabine/therapeutic use , Zidovudine/therapeutic use , Administration, Oral , Animals , Disease Models, Animal , Drug Therapy, Combination , Female , Mice , Mice, Inbred C57BL , Zalcitabine/administration & dosage , Zidovudine/administration & dosageABSTRACT
Using the murine LP-BM5 retrovirus-induced immunodeficiency model, the therapeutic value of zidovudine (AZT) was analyzed. Continuous low dose (60 mg/kg per day) oral AZT administration for 6 weeks increased survival time by 5-6 weeks. Decreasing the duration of therapy to 3 weeks decreased the mean survival time. Extending the therapy from 6 to 14 weeks increased the median survival time (8 weeks). This dose was nontoxic and reduced virus titers, splenomegaly, and lymphadenopathy. AZT also retarded the immune dysfunction syndrome characteristic of this model. Hypergammaglobulinemia was reduced by AZT and was also a marker for disease progression. AZT reduced hyperproliferation of large blast cells and delayed the loss of splenic B cells.
Subject(s)
Immunologic Deficiency Syndromes/drug therapy , Leukemia Virus, Murine/drug effects , Leukemia, Experimental/drug therapy , Zidovudine/therapeutic use , Acquired Immunodeficiency Syndrome/drug therapy , Animals , Cell Separation , Disease Models, Animal , Female , Flow Cytometry , Immunoglobulin G/biosynthesis , Immunoglobulin M/biosynthesis , Lymph Nodes/microbiology , Lymph Nodes/pathology , Mice , Mice, Inbred C57BL , Organ Size , Spleen/microbiology , Spleen/pathologyABSTRACT
Due to its size, Barnes Hospital had a logjam of asynchronous data. Lab interface workstations are used to alleviate the problem.
