Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy

J Infect Dis. 2008 Feb 15;197(4):563-71. doi: 10.1086/526786.


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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / virology
  • Cohort Studies
  • Female
  • Gene Products, gag / immunology
  • HIV Infections* / genetics
  • HIV Infections* / immunology
  • HIV Long-Term Survivors*
  • HIV-1 / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Male
  • Middle Aged
  • RNA, Viral
  • Viral Load
  • Viremia / genetics*
  • Viremia / immunology


  • Gene Products, gag
  • Interleukin-2
  • RNA, Viral
  • Interferon-gamma