Administration of Fludarabine-loaded Autologous Red Blood Cells in Simian Immunodeficiency Virus-infected Sooty Mangabeys Depletes Pstat-1-expressing Macrophages and Delays the Rebound of Viremia After Suspension of Antiretroviral Therapy.
From: Institute of Biochemistry, University of Urbino, Urbino, Italy.
Journal of virology
- Publish Date: Nov 2006
- ISSN: 0022-538X
- Volume: 80
- Issue: 21
- Pages: 10335-45
- Medium: Print
- Language: English
- Citation (JAMA): Cervasi B, Paiardini M, Serafini S, et al. Administration of Fludarabine-loaded Autologous Red Blood Cells in Simian Immunodeficiency Virus-infected Sooty Mangabeys Depletes Pstat-1-expressing Macrophages and Delays the Rebound of Viremia After Suspension of Antiretroviral Therapy.. J. Virol. Nov 2006;80:10335-45
Abstract
A major limitation of highly active antiretroviral therapy is that it fails to eradicate human immunodeficiency virus (HIV) infection due to its limited effects on viral reservoirs carrying replication-competent HIV, including monocytes/macrophages (M/M). Therefore, therapeutic approaches aimed at targeting HIV-infected M/M may prove useful in the clinical management of HIV-infected patients. In previous studies, we have shown that administration of fludarabine-loaded red blood cells (RBC) in vitro selectively induces cell death in HIV-infected M/M via a pSTAT1-dependent pathway. To determine the in vivo efficacy of this novel therapeutic strategy, we treated six naturally simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) with either 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) only, fludarabine-loaded RBC only, or PMPA in association with fludarabine-loaded RBC. The rationale of this treatment was to target infected M/M with fludarabine-loaded RBC at a time when PMPA is suppressing viral replication taking place in activated CD4+ T cells. In vivo administration of fludarabine-loaded RBC was well tolerated and did not induce any discernible side effect. Importantly, addition of fludarabine-loaded RBC to PMPA delayed the rebound of viral replication after suspension of therapy, thus suggesting a reduction in the size of SIV reservoirs. While administrations of fludarabine-loaded RBC did not induce any change in the CD4+ or CD8+ T-cell compartments, we observed, in chronically SIV-infected SMs, a selective depletion of M/M expressing pSTAT1. This study suggests that therapeutic strategies based on the administration of fludarabine-loaded RBC may be further explored as interventions aimed at reducing the size of the M/M reservoirs during chronic HIV infection.
Mesh Headings (Keywords): Adenine, Animals, Antiretroviral Therapy, Highly Active, Antiviral Agents, Cercocebus atys, Drug Carriers, Erythrocytes, Female, Humans, Macrophages, Male, Myeloablative Agonists, Phosphonic Acids, STAT1 Transcription Factor, Simian Acquired Immunodeficiency Syndrome, T-Lymphocyte Subsets, Vidarabine, Viremia, Virus Replication
Check for Full Text / PubMed Unique Identifier (PMID): 17041214
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