Near normalization of peripheral blood markers in HIV-infected patients on long-term suppressive antiretroviral therapy: a case-control study

AIDS. 2020 Nov 1;34(13):1891-1897. doi: 10.1097/QAD.0000000000002645.

Abstract

Objective: To explore the differences in peripheral blood markers between HIV well controlled patients on long-term suppressive antiretroviral therapy (HIV-group) and age-matched healthy controls, to evaluate the benefits of virological suppression in those patients.

Methods: We performed a case-control study in 22 individuals in the HIV-group and 14 in the healthy control-group. RNA-seq analysis was performed from peripheral blood mononuclear cells. Peripheral blood T-cell subsets were evaluated by flow cytometry and plasma biomarkers by immunoassays. All P values were corrected by the false discovery rate (q values).

Results: Only the serine/arginine repetitive matrix 4 gene, which is involved in alternative RNA splicing events, was differentially expressed between HIV and healthy control groups (q value ≤0.05 and fold-change ≥2). However, 147 differentially expressed genes were found with a more relaxed threshold (P value ≤0.05 and fold-change ≥1.5), of which 67 genes with values of variable importance in projection at least one were selected for pathway analysis. We found that six ribosomal genes represented significant ribosome-related pathways, all of them downregulated in the HIV-group, which may be a strategy to facilitate viral production. T cells subset and plasma biomarkers did not show significant differences after false discovery rate correction (q value >0.05), but a noncorrected analysis showed higher values of regulatory CD4 T cells (CD4CD25CD127), MCP-1, and sVEGF-R1 in the HIV-group (P value ≤0.05).

Conclusion: T-cell subsets, plasma biomarkers, and gene expression were close to normalization in HIV-infected patients on long-term suppressive combination antiretroviral therapy compared with healthy controls. However, residual alterations remain, mainly at the gene expression, which still reveals the impact of HIV infection in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Biomarkers / blood
  • Case-Control Studies
  • DNA, Viral / analysis
  • Female
  • HIV Infections / blood*
  • HIV Infections / drug therapy*
  • HIV-1 / genetics*
  • Humans
  • Leukocytes, Mononuclear
  • Male
  • Middle Aged
  • RNA-Seq

Substances

  • Anti-HIV Agents
  • Anti-Retroviral Agents
  • Biomarkers
  • DNA, Viral