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 depletio...

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Bibliographic Details
Published in:Antiviral research 2009-02, Vol.81 (2), p.93-102
Main Authors: Serafini, S., Fraternale, A., Rossi, L., Casabianca, A., Antonelli, A., Paoletti, M.F., Orlandi, C., Pierigè, F., Sfara, C., Schiavano, G.F., Magnani, M.
Format: Article
Language:English
Subjects:
Animals
Anti-HIV Agents - administration & dosage
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Biological and medical sciences
Clodronic Acid - administration & dosage
Didanosine - administration & dosage
DNA, Viral - blood
Drug delivery
Female
HIV reservoirs
Human immunodeficiency virus 1
Human viral diseases
Immunodeficiencies
Immunodeficiencies. Immunoglobulinopathies
Immunologic Factors - administration & dosage
Immunopathology
Infectious diseases
Leukocyte Reduction Procedures
Loaded erythrocytes
Macrophages
Macrophages - immunology
MAIDS
Medical sciences
Mice
Mice, Inbred C57BL
Murine Acquired Immunodeficiency Syndrome - drug therapy
Murine Acquired Immunodeficiency Syndrome - immunology
Pharmacology. Drug treatments
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
Viral Load
Zidovudine - administration & dosage
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Summary: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.
ISSN:0166-3542
1872-9096
DOI:10.1016/j.antiviral.2008.09.006