Abstract
Human immunodeficiency virus (HIV) infection is characterized by a progressive loss of memory CD4(+) T cells in multiple tissues, especially at mucosal surfaces where most of these cells reside. Although antiretroviral therapy (ART) suppresses viral replication and promotes the recovery of peripheral CD4(+) T cells, HIV-infected patients fail to fully reconstitute the CD4(+) T-cell pool at mucosal sites. IL-15 has been shown to preferentially expand memory-phenotype T cells and promote their migration to nonlymphoid tissues. Here we examined IL-15 treatment in combination with highly active ART in chronically SIV-infected rhesus macaques and found that IL-15 delayed viral suppression and failed to enhance ART-induced total and antigen-specific CD4(+) T-cell reconstitution at mucosal and lymphoid sites. IL-15 was able to induce the transient proliferation of SIV-specific, CMV-specific, and total memory CD8(+) T cells, but not of SIV-specific or total CD4(+) T cells. Moreover, upon treatment interruption, macaques receiving combined IL-15+ART lost CD4(+) T cells faster than those receiving ART alone. These results suggest that the combination of IL-15 with highly active ART is not more efficient than ART alone in promoting CD4(+) T-cell recovery in HIV-infected individuals and may accelerate CD4+ T-cell loss after treatment interruption.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
MeSH terms
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Adaptive Immunity / drug effects
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Adenine / administration & dosage
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Adenine / analogs & derivatives*
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Adenine / pharmacology
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Adenine / therapeutic use
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Animals
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Anti-Retroviral Agents / administration & dosage
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Anti-Retroviral Agents / pharmacology
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Anti-Retroviral Agents / therapeutic use*
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Antiretroviral Therapy, Highly Active
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CD4 Lymphocyte Count
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CD4-Positive T-Lymphocytes / drug effects*
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CD4-Positive T-Lymphocytes / immunology
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Deoxycytidine / administration & dosage
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / pharmacology
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Deoxycytidine / therapeutic use
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Drug Evaluation, Preclinical
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Drug Therapy, Combination
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Emtricitabine
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Immunity, Mucosal / drug effects
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Immunologic Factors / administration & dosage
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Immunologic Factors / adverse effects
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Immunologic Factors / pharmacology
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Immunologic Factors / therapeutic use*
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Immunotherapy
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Interleukin-15 / administration & dosage
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Interleukin-15 / adverse effects
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Interleukin-15 / pharmacology
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Interleukin-15 / therapeutic use*
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Lymphocyte Activation
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Lymphoid Tissue / immunology
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Lymphoid Tissue / pathology
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Macaca mulatta
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Mucous Membrane / immunology
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Mucous Membrane / pathology
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Organophosphonates / administration & dosage
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Organophosphonates / pharmacology
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Organophosphonates / therapeutic use*
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Pyrrolidinones / administration & dosage
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Pyrrolidinones / pharmacology
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Pyrrolidinones / therapeutic use*
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Raltegravir Potassium
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Random Allocation
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Simian Acquired Immunodeficiency Syndrome / immunology*
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Tenofovir
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Treatment Failure
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Viral Load
Substances
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Anti-Retroviral Agents
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Immunologic Factors
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Interleukin-15
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Organophosphonates
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Pyrrolidinones
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Deoxycytidine
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Raltegravir Potassium
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Tenofovir
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Emtricitabine
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Adenine