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.
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.
Choudhary
Shailesh K
SK
Department of Medicine, University of North Carolina, Chapel Hill, 27599, USA. schoudha@med.unc.edu
Rezk
Naser L
NL
Ince
William L
WL
Cheema
Manzoor
M
Zhang
Liguo
L
Su
Lishan
L
Swanstrom
Ronald
R
Kashuba
Angela D M
AD
Margolis
David M
DM
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
D004268:DNA-Binding Proteins; D019429:Integrase Inhibitors; C499308:Rag2 protein, mouse; D018894:Reverse Transcriptase Inhibitors