Repeated cycles of alternate administration of fludarabine and Zidovudine plus Didanosine inhibits murine AIDS and reduces proviral DNA content in lymph nodes to undetectable levels.
The results of the combined use of Fludarabine, an anticancer agent that may be able to target latently infected cells, and conventional antiretroviral therapy (AZT+DDI) in a murine model of AIDS, i.e., LP-BM5 infection, are reported. Eighty percent of infected mice, treated with four cycles of alternate administration of Fludarabine and AZT+DDI, showed undetectable levels of proviral DNA in lymph nodes. After 8 weeks of treatment interruption, the infected/treated animals, although still alive at a time when all untreated animals had succumbed to the infection, showed disease progression and reappearance of proviral DNA in lymph nodes. The retrospective analysis of proviral DNA content in spleen and bone marrow at the end of the fourth cycle of treatment revealed a low but detectable amount of BM5d proviral DNA. We thus concluded that the spleen and bone marrow may be less sensitive to lympholitic drugs and therefore act as viral reservoirs in LP-BM5 infection. This study suggests that optimized protocols of alternate administration of cytolytic and antiretroviral drugs may represent a useful strategy to eradicate retroviral infections.
Fraternale
Alessandra
A
Institute of Biological Chemistry Giorgio Fornaini, University of Urbino, 61029 Urbino, Italy.
Casabianca
Anna
A
Orlandi
Chiara
C
Chiarantini
Laura
L
Brandi
Giorgio
G
Silvestri
Guido
G
Magnani
Mauro
M
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004279:DNA, Viral / Q000032:analysis; D016049:Didanosine / Q000008:administration & dosage / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D009052:Leukemia Virus, Murine / Q000187:drug effects*; D008198:Lymph Nodes / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D011533:Proviruses; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D014740:Vidarabine; D016049:Didanosine; C024352:fludarabine