Lack of correlation between the size of HIV proviral DNA reservoir and the level of immune activation in HIV-infected patients with a sustained undetectable HIV viral load for 10 years

J Clin Virol. 2013 Aug;57(4):351-5. doi: 10.1016/j.jcv.2013.04.007. Epub 2013 May 8.

Abstract

Background: The persistence of HIV residual replication in patients with an undetectable plasma viral load (pVL) may limit immune recovery and facilitate inflammation-induced comorbidities.

Objective: The objective was to evaluate any correlation between immune restoration and intracellular [IC] HIV-DNA in cART-treated patients with a sustained undetectable pVL.

Study design: This retrospective cross sectional study included 62 patients with a median duration of undetectable pVL of 10.3 years. IC HIV DNA in peripheral mononuclear blood cells (PBMCs) and T cell subsets were measured at the last visit. pVL, CD4(+) and CD8(+) T cell counts were retrospectively collected from the onset of long-term inhibition by antiretroviral treatment. The patients were separated into two groups: 27 non-blippers (sustained pVL< threshold value during all the visits) and 35 blippers ( ≥ 1 episodes of pVL> threshold but < 1000 copies/ml). The median pVL in blippers was 115 copies/ml.

Results: The median IC HIV DNA rate was 34 copies/10(6) PBMCs (71% ≥ 20 copies/10(6) PBMCs) with no significant difference between the groups. The proportion of CD8(+)CD38(+) and CD8(+)DR(+) T cells was higher in blipper patients, but the difference was only significant for the CD8(+)DR(+) marker (p = 0.036). No correlation was found between markers of immune activation on CD4(+) and CD8(+) T cells and the IC HIV-DNA level.

Conclusion: No relation was found between the size of HIV reservoirs and immune activation in patients with sustained undetectable pVL. Mechanisms of immune activation have to be better understood in order to define specific therapeutic interventions.

MeSH terms

  • Adult
  • Anti-HIV Agents / immunology
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / methods
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cross-Sectional Studies
  • DNA, Viral / genetics
  • DNA, Viral / immunology*
  • Female
  • HIV / genetics*
  • HIV / immunology*
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • RNA, Viral / immunology
  • Retrospective Studies
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / virology
  • Viral Load / immunology

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • RNA, Viral