title: Augmentation of HIV-1-specific T helper cell responses in chronic HIV-1 infection by therapeutic immunization.
abstract: OBJECTIVE
  To determine whether therapeutic immunization with a whole inactivated HIV-1 immunogen augments HIV-1-specific T helper cell responses in chronically infected individuals receiving suppressive antiretroviral therapy (ART).
  
  
  METHODS
  An investigator-initiated, single center, double-blind, placebo-controlled, randomized trial.
  
  
  METHODS
  Subjects selected for study were HIV-1-infected adults on ART with an HIV-1-RNA plasma viral load of less than 500 copies/ml for at least 6 months, and a CD4 cell count greater than 250 cells/mm3 before starting ART. Study subjects were randomly assigned to receive either immunogen (inactivated envelope-depleted HIV-1 coupled with incomplete Freund's adjuvant; IFA), versus placebo (IFA alone). The primary outcome was significant CD4 cell lymphoproliferative responses to HIV-1 proteins. Secondary endpoints included HIV-1-specific CD8 T cell responses, CD4 cell count/percentage, HIV-1-RNA plasma viral load, and delayed-type hypersensitivity (DTH) responses.
  
  
  RESULTS
  The augmentation of HIV-1-specific T helper cell responses was achieved in five out of five vaccine recipients and none out of four controls (P = 0.008, Fisher's exact test). There were no significant changes in the breadth or magnitude of cytotoxic T lymphocyte responses, CD4 cell count/percentages, or DTH test responses.
  
  
  CONCLUSIONS
  HIV-1-specific T helper cell responses can be successfully increased by therapeutic immunization in individuals with chronic infection on suppressive ART. Further studies will be needed to determine whether the augmentation of these responses correlate with long-term clinical benefits.
authors.affiliation: Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, Division of AIDS Harvard Medical School, Boston, 02114, USA.
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.forename: Marylyn M
authors.initials: MM
authors.lastname: Addo
authors.forename: Hien
authors.initials: H
authors.lastname: Troung
authors.forename: Almas
authors.initials: A
authors.lastname: Rathod
authors.forename: Kathy
authors.initials: K
authors.lastname: Habeeb
authors.forename: Benjamin
authors.initials: B
authors.lastname: Davis
authors.forename: Howard
authors.initials: H
authors.lastname: Heller
authors.forename: Nesli
authors.initials: N
authors.lastname: Basgoz
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
mesh_terms: D016915:AIDS Vaccines / Q000627:therapeutic use*; D000328:Adult; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D003602:Cytotoxicity, Immunologic; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015497:HIV-1; D006801:Humans; D007114:Immunization; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; C105086:remune