title: CD4+ T cell receptor repertoire perturbations in HIV-1 infection: association with plasma viremia and disease progression.
abstract: CD4+ T cell depletion and dysfunction are the hallmark of HIV-1 disease. Our primary objectives were to define the diversity of the CD4+ T cell receptor Vbeta (TCRBV) repertoire in subjects with HIV-1 infection by CDR3 (complementarity-determining region) length spectratyping and to determine the correlates of CD4+ repertoire perturbation and its restoration with virus suppression. During primary HIV-1 infection, the proportion of perturbed CD4+ TCRBV subfamilies was significantly greater compared to HIV-1 seronegative subjects (median 48% vs. 10%, P = 0.0159). During chronic infection, the extent of repertoire perturbation was significantly associated with higher levels of plasma viremia (Spearman Correlation coefficient, R = 0.65, P = 0.049) and disease progression. Restoration of the repertoire with antiretroviral therapy was variable despite adequate virologic suppression. We speculate that the use of immunomodulators as an adjunct to antiretroviral drugs may enhance immune reconstitution in persons with suboptimal increases in CD4+ T cell counts despite adequate virus suppression.
authors.affiliation: Program in Infectious Diseases, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. uma@u.washington.edu
authors.forename: Uma
authors.initials: U
authors.lastname: Malhotra
authors.forename: Claire
authors.initials: C
authors.lastname: Huntsberry
authors.forename: Sarah
authors.initials: S
authors.lastname: Holte
authors.forename: Jean
authors.initials: J
authors.lastname: Lee
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics; D018450:Disease Progression; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology*
chemical_list: D044966:Anti-Retroviral Agents; D022801:Complementarity Determining Regions; D012367:RNA, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta