Effect of macrophage depletion on viral DNA rebound following antiretroviral therapy in a murine model of AIDS (MAIDS).
In the attempt to eradicate HIV-1 infection, a strategy to eliminate macrophages, one of the most important cellular reservoirs in sustaining virus replication during HAART, could be of great benefit in the suppression of viral rebound. Aware of the ability of clodronate to cause macrophage depletion, the effect of the administration of clodronate encapsulated in erythrocytes on disease progression and on viral rebound was evaluated in a murine model of AIDS (MAIDS). One group of LP-BM5 retroviral complex-infected C57BL/6 mice received oral administrations of azidothymidine and dideoxyinosine daily for 12 weeks; two other groups received in addition, either clodronate-loaded erythrocytes or free clodronate at 7-10 day intervals. At the end of the treatment, the three groups maintained parameters characterizing disease progression similar to those of uninfected mice and showed a significantly lower level of BM5d DNA than infected mice in all organs and cells tested. To assess the viral rebound, some animals were left for an additional 4 month period without any treatment. After this time, the BM5d DNA content in blood leukocytes increased in all groups, but the group having received clodronate-loaded erythrocytes, in addition to transcriptase inhibitors, showed a significant delay in viral rebound.
Serafini
S
S
Institute of Biological Chemistry G. Fornaini, University of Urbino, Via Saffi, 2-61029 Urbino (PU), Italy.
Fraternale
A
A
Rossi
L
L
Casabianca
A
A
Antonelli
A
A
Paoletti
M F
MF
Orlandi
C
C
Pierigè
F
F
Sfara
C
C
Schiavano
G F
GF
Magnani
M
M
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage; D004002:Clodronic Acid / Q000008:administration & dosage; D004279:DNA, Viral / Q000097:blood*; D016049:Didanosine / Q000008:administration & dosage; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage; D047589:Leukocyte Reduction Procedures; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage
D019380:Anti-HIV Agents; D004279:DNA, Viral; D007155:Immunologic Factors; D004002:Clodronic Acid; D015215:Zidovudine; D016049:Didanosine