Abstract
A small animal model that reproduces human immunodeficiency virus type 1 (HIV-1) pathogenesis may allow modeling of new therapeutic strategies in ways not approachable in mononuclear cell culture. We find that, as in humans, combination antiretroviral therapy (ART) in humanized (hu-) Rag2(-/-)gamma(c)(-/-) mice allows suppression of viremia below the limits of detection and recovery of CD4(+) cells, while interruption of ART results in viral rebound and renewed loss of CD4(+) T cells. Failure of ART in infected mice is associated with the appearance of drug resistance mutations. The hu-Rag2(-/-)gamma(c)(-/-) mouse may therefore facilitate testing of novel approaches to HIV replication and persistence.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / drug effects*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / virology
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Disease Models, Animal
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Drug Therapy, Combination
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HIV Infections / drug therapy*
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HIV Infections / immunology
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HIV Infections / virology
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HIV-1 / drug effects*
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HIV-1 / immunology
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HIV-1 / physiology
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Humans
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Integrase Inhibitors / therapeutic use*
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Mice
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Mice, Knockout
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Reverse Transcriptase Inhibitors / therapeutic use*
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Viremia / drug therapy*
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Viremia / immunology
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Viremia / pathology
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Viremia / virology
Substances
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DNA-Binding Proteins
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Integrase Inhibitors
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Rag2 protein, mouse
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Reverse Transcriptase Inhibitors