Changes in Markers of T-Cell Senescence and Exhaustion With Atazanavir-, Raltegravir-, and Darunavir-Based Initial Antiviral Therapy: ACTG 5260s

J Infect Dis. 2016 Sep 1;214(5):748-52. doi: 10.1093/infdis/jiw253. Epub 2016 Jun 28.

Abstract

It is unclear whether differential roles of CD4(+) versus CD8(+) T-cell senescence/exhaustion and effects of antiretroviral therapy (ART) on these processes may contribute to morbidity in treated human immunodeficiency virus type 1 (HIV) infection. In a prospective 96-week trial, 328 HIV-infected ART-naive participants were randomly assigned to receive tenofovir-emtricitabine plus either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir. Markers of CD4(+) T-cell senescence (ie, the percentage of CD28(-)CD57(+) cells among CD4(+) T cells ) and CD4(+)/CD8(+) T-cell exhaustion (ie, the percentage of PD-1(+) cells among CD4(+)/CD8(+) T cells) decreased after ART. There were no changes in markers of CD8(+) T-cell senescence after ART and no differential changes in all markers in ART groups. Senescent CD4(+) and CD8(+) T cells may have differential roles in HIV pathogenesis.

Keywords: antiretroviral therapy; biomarkers; human immunodeficiency virus; immune activation; inflammation.

Publication types

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

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antigens, CD / analysis
  • Atazanavir Sulfate / therapeutic use*
  • Darunavir / therapeutic use*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • Humans
  • Immunophenotyping
  • Male
  • Prospective Studies
  • Raltegravir Potassium / therapeutic use*
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / immunology*

Substances

  • Anti-HIV Agents
  • Antigens, CD
  • Raltegravir Potassium
  • Atazanavir Sulfate
  • Darunavir