Impact of monotherapy on HIV-1 reservoir, immune activation, and co-infection with Epstein-Barr virus

PLoS One. 2017 Sep 19;12(9):e0185128. doi: 10.1371/journal.pone.0185128. eCollection 2017.

Abstract

Objectives: Although monotherapy (mART) effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV) is unclear.

Methods: This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART) over the same period of time were included in the study. Markers of HIV-1 reservoir (HIV-1 DNA and intracellular HIV-1 RNA) were quantified by real-time PCR. Markers of T-(CD3+CD8+CD38+) and B-(CD19+CD80/86+ and CD19+CD10-CD21lowCD27+) cell activation were evaluated by flow cytometry. Plasma levels of microbial translocation markers were quantified by real-time PCR (16S ribosomal DNA and mitochondrial [mt]DNA) or by ELISA (LPS and sCD14). EBV was typed and quantified by multiplex real-time PCR.

Results: At baseline, no differences were found between mART and cART groups. Three (10%) mART-treated patients had a virological failure vs none in the cART group. Levels of HIV-1 DNA, intracellular HIV-1 RNA and EBV-DNA remained stable in the mART group, while decreased significantly in the cART group. Percentages of T- and B-activated cells significantly increased in the mART-treated patients, while remained at low levels in the cART-treated ones (p = 0.014 and p<0.001, respectively). Notably, levels of mtDNA remained stable in the cART group, but significantly rose in the mART one (p<0.001).

Conclusions: Long-term mART is associated with higher levels of T- and B-cell activation and, conversely to cART, does not reduce the size of HIV-1 reservoir and EBV co-infection.

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Coinfection / pathology
  • Coinfection / virology
  • DNA, Mitochondrial / metabolism
  • DNA, Viral / analysis
  • DNA, Viral / metabolism
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Infections / virology
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Leukocytes, Mononuclear / virology
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • RNA, Viral / analysis
  • RNA, Viral / metabolism
  • Retrospective Studies
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

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

Grants and funding

This study was supported by Associazione Italiana per la Ricerca sul Cancro, grant no. IG-14258 and grant no. IG-19112.