Protease inhibitor monotherapy is associated with a higher level of monocyte activation, bacterial translocation and inflammation

J Int AIDS Soc. 2014 Sep 29;17(1):19246. doi: 10.7448/IAS.17.1.19246. eCollection 2014.

Abstract

Introduction: Monotherapy with protease-inhibitors (MPI) may be an alternative to cART for HIV treatment. We assessed the impact of this strategy on immune activation, bacterial translocation and inflammation.

Methods: We performed a cross-sectional study comparing patients on successful MPI (n=40) with patients on cART (n=20). Activation, senescence, exhaustion and differentiation stage in CD4+ and CD8+ T lymphocyte subsets, markers of monocyte activation, microbial translocation, inflammation, coagulation and low-level viremia were assessed.

Results: CD4+ or CD8+ T lymphocyte subset parameters were not significantly different between both groups. Conversely, as compared with triple cART, MPI patients showed a higher proportion of activated monocytes (CD14+ CD16-CD163+ cells, p=0.031), soluble markers of monocyte activation (sCD14 p=0.004, sCD163 p=0.002), microbial translocation (lipopolysaccharide (LPS)-binding protein; LBP p=0.07), inflammation (IL-6 p=0.04) and low-level viremia (p=0.035). In a multivariate model, a higher level of CD14+ CD16-CD163+ cells and sCD14, and presence of very low-level viremia were independently associated with MPI. Monocyte activation was independently associated with markers of inflammation (IL-6, p=0.006), microbial translocation (LBP, p=0.01) and low-level viremia (p=0.01).

Conclusions: Patients on MPI showed a higher level of monocyte activation than patients on standard therapy. Microbial translocation and low-level viremia were associated with the high level of monocyte activation observed in patients on MPI. The long-term clinical consequences of these findings should be assessed.

Keywords: immune activation; microbial translocation; monocyte; monotherapy; protease inhibitor; very low-level viremia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Bacterial Translocation*
  • Blood Coagulation
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cross-Sectional Studies
  • Female
  • GPI-Linked Proteins / analysis
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Protease Inhibitors / therapeutic use*
  • Humans
  • Inflammation / epidemiology*
  • Lipopolysaccharide Receptors / analysis
  • Male
  • Middle Aged
  • Monocytes / chemistry
  • Monocytes / immunology*
  • Receptors, Cell Surface / analysis
  • Receptors, IgG / analysis
  • Viremia

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • HIV Protease Inhibitors
  • Lipopolysaccharide Receptors
  • Receptors, Cell Surface
  • Receptors, IgG