Cell-based measures of viral persistence are associated with immune activation and programmed cell death protein 1 (PD-1)-expressing CD4+ T cells

J Infect Dis. 2013 Jul;208(1):50-6. doi: 10.1093/infdis/jis630. Epub 2012 Oct 22.


Background: Studies aimed at defining the association between host immune responses and human immunodeficiency virus (HIV) persistence during therapy are necessary to develop new strategies for cure.

Methods: We performed a comprehensive assessment of ultrasensitive plasma HIV RNA levels, cell-associated HIV RNA levels, proviral HIV DNA levels, and T cell immunophenotyping in a cohort of 190 subjects in whom HIV levels were suppressed by highly active antiretroviral therapy.

Results: The median CD4(+) T cell count was 523 cells/mm(3), and the median duration of viral suppression was 31 months. Cell-associated RNA and proviral DNA levels (but not ultrasensitive plasma HIV RNA levels) were positively correlated with frequencies of CD4(+) and CD8(+) T cells expressing markers of T-cell activation/dysfunction (CD38, HLA-DR, CCR5, and/or programmed cell death protein 1 [PD-1]) (P < .05). Having a low CD4(+) T-cell count despite receipt of virologically suppressive therapy was associated with high cell-associated RNA and proviral DNA levels (P < .01) and higher frequencies of CD4(+) T cells expressing CD38, HLA-DR, CCR5, and/or PD-1 (P < .0001).

Conclusions: Cell-based measurements of viral persistence were consistently associated with markers of immune activation and the frequency of PD-1-expressing CD4(+) T cells. Treated patients with a low CD4(+) T-cell count had higher frequencies of PD-1-expressing CD4(+) T cells and cell-based measures of viral persistence, suggesting that HIV infection in these individuals may be more difficult to cure and may require unique interventions.

Keywords: 2-LTR circles; D-dimer; HIV; ongoing viral replication; raltegravir intensification.

Publication types

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

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • DNA, Viral / drug effects
  • Female
  • HIV / drug effects*
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / virology
  • Humans
  • Immunity, Cellular / drug effects
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / blood*
  • Proviruses / drug effects
  • RNA, Viral / blood


  • DNA, Viral
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • RNA, Viral