Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point

Immunity. 2015 Sep 15;43(3):591-604. doi: 10.1016/j.immuni.2015.08.012. Epub 2015 Sep 8.


CD8(+) T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified 12 hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8(+) T cell response, with limited bystander activation of non-HIV memory CD8(+) T cells. HIV-specific CD8(+) T cells secreted little interferon-γ, underwent rapid apoptosis, and failed to upregulate the interleukin-7 receptor, known to be important for T cell survival. The rapidity to peak CD8(+) T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8(+) T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design.

Publication types

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

MeSH terms

  • Adolescent
  • Apoptosis / immunology
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Female
  • Flow Cytometry
  • HIV Infections / blood
  • HIV Infections / diagnosis
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / physiology
  • Humans
  • Kinetics
  • Lymphocyte Activation / immunology*
  • Proto-Oncogene Proteins c-bcl-2 / immunology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Viral / genetics
  • RNA, Viral / immunology
  • Time Factors
  • Viral Load / immunology*
  • Viremia / diagnosis
  • Viremia / immunology
  • Young Adult
  • fas Receptor / immunology
  • fas Receptor / metabolism


  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Viral
  • fas Receptor