Immune activation, CD4+ T cell counts, and viremia exhibit oscillatory patterns over time in patients with highly resistant HIV infection

PLoS One. 2011;6(6):e21190. doi: 10.1371/journal.pone.0021190. Epub 2011 Jun 20.

Abstract

The rates of immunologic and clinical progression are lower in patients with drug-resistant HIV compared to wild-type HIV. This difference is not fully explained by viral load. It has been argued that reductions in T cell activation and/or viral fitness might result in preserved target cells and an altered relationship between the level of viremia and the rate of CD4+ T cell loss. We tested this hypothesis over time in a cohort of patients with highly resistant HIV. Fifty-four antiretroviral-treated patients with multi-drug resistant HIV and detectable plasma HIV RNA were followed longitudinally. CD4+ T cell counts and HIV RNA levels were measured every 4 weeks and T cell activation (CD38/HLA-DR) was measured every 16 weeks. We found that the levels of CD4+ T cell activation over time were a strong independent predictor of CD4+ T cell counts while CD8+ T cell activation was more strongly associated with viremia. Using spectral analysis, we found strong evidence for oscillatory (or cyclic) behavior in CD4+ T cell counts, HIV RNA levels, and T cell activation. Each of the cell populations exhibited an oscillatory behavior with similar frequencies. Collectively, these data suggest that there may be a mechanistic link between T cell activation, CD4+ T cell counts, and viremia and lends support for the hypothesis of altered predator-prey dynamics as a possible explanation of the stability of CD4+ T cell counts in the presence of sustained multi-drug resistant viremia.

Publication types

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

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count*
  • Drug Resistance, Multiple, Viral / genetics
  • Drug Resistance, Multiple, Viral / immunology*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Viremia / drug therapy
  • Viremia / immunology

Substances

  • Anti-HIV Agents