title: Peripheral T-cell apoptosis is not differentially affected by antiretroviral regimens in HIV-infected patients.
abstract: BACKGROUND
  HIV-induced CD4(+) and CD8(+) T-cell apoptosis decreases upon start of combination antiretroviral therapy (cART). Although in vitro evidence suggests an anti-apoptotic effect of protease inhibitors (PIs) as opposed to non-nucleoside reverse transcriptase inhibitors (NNRTIs), in vivo studies are inconclusive about effects of differential cART regimens on T-cell apoptosis.
  
  
  METHODS
  Peripheral T-cell apoptosis was evaluated in a cross-sectional study including 20 patients on PI- and 19 on NNRTI-based combination antiretroviral therapy (cART), all with backbone therapy of tenofovir and emtricitabine and undetectable viral loads 6 months before inclusion. Spontaneous T-cell apoptosis was measured in freshly isolated peripheral blood mononuclear cells (<4 h after venipuncture) using annexin V, propidium iodide and staining for caspase activity and levels of the anti-apoptotic protein Bcl-2.
  
  
  RESULTS
  The groups were comparable in general- and HIV-specific characteristics. In addition, T-cell activation was similar in both groups. We observed no difference in T-cell apoptosis as measured by annexin V, propidium iodide or caspase staining between PI- and NNRTI-treated patients. Interestingly, the level of anti-apoptotic protein Bcl-2 was higher in PI-treated than in NNRTI-treated patients.
  
  
  CONCLUSIONS
  In this cross-sectional study on HIV-infected patients, direct ex vivo spontaneous T-cell apoptosis rates are not differentially affected by NNRTI- or PI-based cART.
authors.affiliation: Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Feuth
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
authors.forename: Andy I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: Joop E
authors.initials: JE
authors.lastname: Arends
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003430:Cross-Sectional Studies; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D000068698:Tenofovir; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D019253:Proto-Oncogene Proteins c-bcl-2; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine