title: HIV-1 evolution in patients undergoing immunotherapy with Tat, Rev, and Nef expressing dendritic cells followed by treatment interruption.
abstract: OBJECTIVE
  This study aimed to evaluate HIV sequence evolution in whole genes and in CD8 T-cell epitope regions following immunotherapy and subsequent analytical treatment interruption (ATI). A second objective of this study was to analyze associations between vaccine-specific immune responses and epitope mutation rates.
  
  
  METHODS
  HIV-1-infected patients on combined antiretroviral therapy (cART) were subjected to immunotherapy by the administration of an autologous dendritic cell-based therapeutic vaccine expressing Tat, Rev, and Nef and subsequent ATI.
  
  
  METHODS
  HIV-1 genes were amplified and sequenced from plasma RNA obtained before initiation of cART as well as during ATI. Control sequences for virus evolution in untreated HIV-1-infected individuals were obtained from the HIV Sequence Database (Los Alamos). CD8 T-cell epitope regions were defined based on literature data and prediction models. HIV-1-specific immune responses were evaluated to analyze their impact on sequence evolution.
  
  
  RESULTS
  Viral sequence evolution in the tat, rev, and nef genes of vaccinated patients was similar to that of controls. The number of mutations observed inside and outside CD8 T-cell epitopes was comparable for vaccine-targeted and nontargeted proteins. We found no evidence for an impact of vaccine-induced or enhanced immune responses on the number of mutations inside or outside epitopes.
  
  
  CONCLUSIONS
  Therapeutic vaccination of HIV-1-infected patients with a dendritic cell-based vaccine targeting Tat, Rev, and Nef did not affect virus evolution at the whole gene level nor at the CD8 T-cell epitope level.
authors.affiliation: aDepartment of Viroscience bDepartment of Hospital Pharmacy, Erasmus MC, Rotterdam cTheoretical Biology and Bioinformatics, Utrecht University, Utrecht, the Netherlands dDepartment of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven eLaboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Medical School of the Vrije Universiteit Brussel fDepartment of Internal Medicine and Infectious Diseases, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Anna L
authors.initials: AL
authors.lastname: de Goede
authors.forename: Hanneke W M
authors.initials: HW
authors.lastname: van Deutekom
authors.forename: Bram
authors.initials: B
authors.lastname: Vrancken
authors.forename: Martin
authors.initials: M
authors.lastname: Schutten
authors.forename: Sabine D
authors.initials: SD
authors.lastname: Allard
authors.forename: Carel A
authors.initials: CA
authors.lastname: van Baalen
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.forename: Joeri L
authors.initials: JL
authors.lastname: Aerts
authors.forename: Can
authors.initials: C
authors.lastname: Keşmir
authors.forename: Philippe
authors.initials: P
authors.lastname: Lemey
authors.forename: Rob A
authors.initials: RA
authors.lastname: Gruters
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D019143:Evolution, Molecular; D015658:HIV Infections / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D017422:Sequence Analysis, DNA; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D044966:Anti-Retroviral Agents; D018984:Epitopes, T-Lymphocyte; D012367:RNA, Viral; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1; D054322:tat Gene Products, Human Immunodeficiency Virus