title: Suppression of human immunodeficiency virus type 1 (HIV-1) viremia with reverse transcriptase and integrase inhibitors, CD4+ T-cell recovery, and viral rebound upon interruption of therapy in a new model for HIV treatment in the humanized Rag2-/-{gamma}c-/- mouse.
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.
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill, 27599, USA. schoudha@med.unc.edu
authors.forename: Shailesh K
authors.initials: SK
authors.lastname: Choudhary
authors.forename: Naser L
authors.initials: NL
authors.lastname: Rezk
authors.forename: William L
authors.initials: WL
authors.lastname: Ince
authors.forename: Manzoor
authors.initials: M
authors.lastname: Cheema
authors.forename: Liguo
authors.initials: L
authors.lastname: Zhang
authors.forename: Lishan
authors.initials: L
authors.lastname: Su
authors.forename: Ronald
authors.initials: R
authors.lastname: Swanstrom
authors.forename: Angela D M
authors.initials: AD
authors.lastname: Kashuba
authors.forename: David M
authors.initials: DM
authors.lastname: Margolis
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D006801:Humans; D019429:Integrase Inhibitors / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D014766:Viremia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D004268:DNA-Binding Proteins; D019429:Integrase Inhibitors; C499308:Rag2 protein, mouse; D018894:Reverse Transcriptase Inhibitors