title: Proliferation responses to HIVp24 during antiretroviral therapy do not reflect improved immune phenotype or function.
abstract: OBJECTIVE
  To ascertain whether lymphoproliferation (LP) responses to HIVp24 in chronically infected patients treated with antiretroviral therapy (ART) predict an improved cytolytic T-cell phenotype or better in vivo immune function as measured by immunization responses.
  
  
  METHODS
  HIV-infected patients who started ART during chronic infection and who achieved viral suppression (HIV-RNA < 400 copies/ml for > 12 months) were grouped by the presence of strong [stimulation index (SI) > 10; n = 21] or absent (SI < 3; n = 18) LP to HIV-core antigen. The two groups were compared for functional immune responses to vaccination with diphtheria-toxoid, tetanus-toxoid and keyhole-limpet-hemocyanin, frequency of circulating naive and memory CD4+ and CD8+ T lymphocytes, maturation phenotype and expression of cytolytic molecules on total and HIV-specific CD8+ T cells, and frequency of memory CD4+ T cells with intracellular HIV-mRNA. Group comparisons were analyzed by non-parametric Mann-Whitney tests. Proportions were estimated by Pearson's chi analysis.
  
  
  RESULTS
  There were no differences between the groups in immune responses to vaccination or in the numbers or phenotype of circulating T cells. In a subgroup of HLA-A2+ or B8+ patients, HIV-reactive CD8+ T cells in both groups had similar expression of perforin, granzyme A and T-cell maturation markers (CD27, CD28, CCR7, CD62L). However, patients with SI > 10 in response to HIVp24 tended to more often have high levels of circulating CD4+ T cells with intracellular HIV-1 mRNA than did patients with SI < 3.
  
  
  CONCLUSIONS
  Following long-standing suppression of viral replication on ART, the presence of HIV-1 specific T-helper proliferation responses does not correlate with improved indices of immune phenotype or function but may reflect relatively higher levels of HIV-expression.
authors.affiliation: Center for AIDS Research, Department of Medicine, Division of Infectious Diseases, Case Western Reserve University, University Hospitals of Cleveland, 2061 Cornell Road, Cleveland, OH 44106, USA.
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Lange
authors.forename: Zhan
authors.initials: Z
authors.lastname: Xu
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Patterson
authors.forename: Kathy
authors.initials: K
authors.lastname: Medvik
authors.forename: Brooke
authors.initials: B
authors.lastname: Harnisch
authors.forename: Robert
authors.initials: R
authors.lastname: Asaad
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Judy
authors.initials: J
authors.lastname: Lieberman
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002908:Chronic Disease; D016655:HIV Core Protein p24 / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014611:Vaccination; D014779:Virus Replication
chemical_list: D016655:HIV Core Protein p24; D012367:RNA, Viral