title: HIV-1-infected individuals in antiretroviral therapy react specifically with polyfunctional T-cell responses to Gag p24.
abstract: BACKGROUND
  Still no effective HIV-1 prophylactic or therapeutic vaccines are available. However, as the proportion of HIV-1-infected individuals on antiretroviral treatment is increasing, knowledge about the residual immune response is important for the possible development of an HIV-1 vaccine.
  
  
  METHODS
  In this study, the magnitude, breadth, and quality of the HIV-1-specific T-cell response in HIV-1-infected viremic individuals (n = 19) and individuals on highly active antiretroviral treatment (HAART) (n = 14) using multicolor flow cytometry were determined.
  
  
  RESULTS
  We found that magnitude and breadth of the CD8 T-cell response were significantly higher in viremic individuals than individuals on HAART (P < 0.0001 and P < 0.0001, respectively) and that the functionality of the overall HIV-1-specific response was significantly different in individuals on HAART and viremic individuals (P = 0.0020). In individuals on HAART, the remaining responses were primarily detected upon stimulation with overlapping peptides from Gag p24, integrase, and Nef. The Gag p24 response was more polyfunctional than corresponding responses observed in viremic individuals.
  
  
  CONCLUSIONS
  Identification of highly immunogenic regions also recognized by individuals on HAART may be important for HIV-1 vaccine development. Irrespective of HLA haplotype, specific regions within the HIV-1 genome that is targeted more frequently in individuals on HAART have been identified. However, further studies are required to establish if these particular regions could be interesting for a future vaccine that might limit the time and opportunity for escape mutations.
authors.affiliation: Department of Virology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Lea
authors.initials: L
authors.lastname: Brandt
authors.forename: Thomas
authors.initials: T
authors.lastname: Benfield
authors.forename: Gitte
authors.initials: G
authors.lastname: Kronborg
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Anders
authors.initials: A
authors.lastname: Fomsgaard
authors.forename: Ingrid
authors.initials: I
authors.lastname: Karlsson
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D019427:HIV Integrase / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D016655:HIV Core Protein p24; D006680:HLA Antigens; D012367:RNA, Viral; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D019427:HIV Integrase