title: Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy.
abstract: BACKGROUND
  Spontaneous control of human immunodeficiency virus (HIV) infection has been documented in a minority of HIV-infected individuals. The mechanisms behind this outcome remain largely unknown, and a better understanding of them will likely influence future vaccine strategies.
  
  
  METHODS
  HIV-specific T cell and antibody responses as well as host genetics were examined in untreated HIV-infected patients who maintain comparatively low plasma HIV RNA levels (hereafter, controllers), including those with levels of < 50 RNA copies/mL (elite controllers, n = 64), those with levels of 50-2000 copies/mL (viremic controllers, n = 60); we also examined HIV-specific T cell and antibody responses as well as host genetics for patients with levels of >10,000 copies/mL (chronic progressors, n = 30).
  
  
  RESULTS
  CD8+ T cells from both controller groups preferentially target Gag over other proteins in the context of diverse HLA class I alleles, whereas responses are more broadly distributed in persons with progressive infection. Elite controllers represent a distinct group of individuals who have significantly more CD4 and CD8 T cells that secrete interferon-gamma and interleukin-2 and lower levels of HIV-neutralizing antibodies. Individual responses were quite heterogeneous, and none of the parameters evaluated was uniquely associated with the ability to control viremia.
  
  
  CONCLUSIONS
  Elite controllers are a distinct group, even when compared to persons with low level viremia, but they exhibit marked genetic and immunologic heterogeneity. Even low-level viremia among HIV controllers was associated with measurable T cell dysfunction, which has implications for current prophylactic vaccine strategies.
authors.affiliation: Partners AIDS Research Center, Massachusetts General Hospital, Boston, MA 02129, USA.
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Marylyn M
authors.initials: MM
authors.lastname: Addo
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Almas
authors.initials: A
authors.lastname: Rathod
authors.forename: Brett
authors.initials: B
authors.lastname: Baker
authors.forename: Alicja
authors.initials: A
authors.lastname: Trocha
authors.forename: Rachel
authors.initials: R
authors.lastname: Rosenberg
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mackey
authors.forename: Peggy
authors.initials: P
authors.lastname: Ueda
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Lu
authors.forename: Daniel
authors.initials: D
authors.lastname: Cohen
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Christos J
authors.initials: CJ
authors.lastname: Petropoulos
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D015331:Cohort Studies; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral; D019562:Viral Load; D014766:Viremia / Q000235:genetics* / Q000276:immunology
chemical_list: D015683:Gene Products, gag; D007376:Interleukin-2; D012367:RNA, Viral; D007371:Interferon-gamma