Effect of cyclophosphamide, total body irradiation, and zidovudine on retrovirus proliferation and disease progression in murine AIDS.
Murine acquired immunodeficiency syndrome (MAIDS) develops when C57B1/6 mice are inoculated with LP-BM5 murine leukemia viruses. Disease progression in these animals is characterized by lymphadenopathy, polyclonal B-cell activation, severe immunodeficiency, and death. Mice with MAIDS have been used to examine the efficacy of antiretroviral therapies for possible use in AIDS patients. In the present work, MAIDS mice were employed to test the hypothesis that established retroviral infection might be cured by the combined use of a cytotoxic agent (cyclophosphamide) and total body irradiation--a regimen reported to have successfully cured HIV-1 infection in one AIDS patient. Results indicate that the ablation of retrovirus-infected lymphoid cells reduced but did not eliminate LP-BM5 infection. Moreover, this regimen was no more effective at controlling virus proliferation or preventing the polyclonal IgG activation characteristic of murine AIDS than was AZT alone.
Klinman
D M
DM
Laboratory of Retrovirus Research, CBER, FDA, Bethesda, MD.
Krieg
A
A
Conover
J
J
Ussery
M A
MA
Black
P L
PL
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D009052:Leukemia Virus, Murine / Q000187:drug effects* / Q000528:radiation effects; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000382:microbiology / Q000532:radiotherapy; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000382:microbiology / Q000532:radiotherapy; D014779:Virus Replication / Q000187:drug effects* / Q000528:radiation effects; D014916:Whole-Body Irradiation; D015215:Zidovudine / Q000494:pharmacology* / Q000627:therapeutic use
D015215:Zidovudine; D003520:Cyclophosphamide