title: Augmented HIV-specific interferon-gamma responses, but impaired lymphoproliferation during interruption of antiretroviral treatment initiated in primary HIV infection.
abstract: BACKGROUND
  Antiretroviral therapy (ART) introduced during primary HIV infection followed by treatment interruption (TI) is postulated to enhance virologic control through induction of HIV-specific CD4 T cells, which foster virus-specific CD8+ T cells that suppress virus replication. This hypothesis was evaluated in 21 subjects enrolled in AIDS Clinical Trials Group 709, a substudy of AIDS Clinical Trials Group 371, which prospectively evaluated subjects who received ≥1 year of ART initiated in acute or recent HIV infection followed by TI.
  
  
  METHODS
  Lymphoproliferation was assessed by [methyl-H] thymidine incorporation and HIV-specific CD8+ T-cell interferon-gamma responses by enzyme-linked immunospot-forming assays. Virologic success was defined as sustained viral load <5000 copies per milliliter for 24 weeks after TI.
  
  
  RESULTS
  HIV-specific lymphoproliferative responses were detected at least once in 5 (24%) of 21 subjects, were generally transient, and were unrelated to HIV-specific interferon-gamma responses (P > 0.4). HIV-specific CD8+ interferon-gamma responses increased after 48 weeks of ART (P = 0.03), but failed to predict virologic success (P = 0.18). Compared with seronegative subjects, lymphoproliferation to Candida, cytomegalovirus, and alloantigens was similar in HIV-infected subjects during ART, but lower during TI (P ≤ 0.04).
  
  
  CONCLUSIONS
  HIV-specific CD8+ T-cell interferon-gamma responses expand during ART following primary HIV infection, but are not related to HIV-specific lymphoproliferative responses nor virologic success. Impaired non-HIV antigen-specific lymphoproliferation associated with TI suggests this strategy could be deleterious.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA. liz.connick@ucdenver
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Connick
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.forename: Evgenia
authors.initials: E
authors.lastname: Aga
authors.forename: Rick
authors.initials: R
authors.lastname: Schlichtemeier
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Demeter
authors.forename: Paul
authors.initials: P
authors.lastname: Volberding
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D000946:Antigens, Fungal / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D004334:Drug Administration Schedule; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D012367:RNA, Viral / Q000097:blood; D014779:Virus Replication
chemical_list: D000942:Antigens, Bacterial; D000946:Antigens, Fungal; D000956:Antigens, Viral; D012367:RNA, Viral; D007371:Interferon-gamma