title: Greater viral rebound and reduced time to resume antiretroviral therapy after therapeutic immunization with the ALVAC-HIV vaccine (vCP1452).
abstract: OBJECTIVE
  Evaluate immunogenicity and clinical efficacy of two immunization strategies with the ALVAC-HIV-recombinant canarypox vaccine (vCP1452) in treated HIV-infected patients.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, phase II study of vCP1452 immunization in chronically HIV-infected patients on therapy with CD4 T-cell count more than 350 cells/microl, CD4 nadir less than 400 cells/microl and pHIV-RNA less than 400 copies/ml. Patients were equally randomized to four injections at weeks 0, 4, 8, 20; three injections at weeks 4, 8, 20; and placebo. The primary endpoint was vaccine immunogenicity at week 24 measured by enzyme-linked immunospot-interferon-gamma against the HIV-gag-reverse transcriptase-nef vaccine sequences. Secondary endpoints included time to treatment resumption and viral quantitation following treatment interruption at week 24. Criteria to resume therapy included CD4 T-cell count decline less than 250 cells/microl or 50% decrease from baseline or pHIV-RNA more than 50,000 copies/ml.
  
  
  RESULTS
  Sixty-five patients enrolled. Changes from baseline in HIV-specific T cells in the four injection arms (+480 spot-forming cells/M-peripheral blood mononuclear cell) were significant compared to placebo (+8; P = 0.014), but not in the three injection arms (+322). The week 36 pHIV-RNA (log10 copies/ml) after treatment interruption was higher in the four (4.71; P = 0.023) and three (4.82; P = 0.009) injection arms compared to placebo (4.40). Percentages of patients reaching treatment resumption criteria by week 48 were 74, 55 and 23% in the three respective arms (P = 0.013). Two independent factors influenced time to therapy resumption: immunization (hazards ratio = 2.7, P = 0.048 for three injections; hazards ratio = 4.1, P = 0.003 for four injections) and CD4 nadir (hazards ratio = 0.4, P = 0.002).
  
  
  CONCLUSIONS
  Significant immunogenicity was induced by vCP1452; however, this strategy was independently associated with a shorter time to resume therapy and higher viral rebound.
authors.affiliation: UPMC Univ Paris 06, UMR_543, France. brigitte.autran@psl.aphp.fr
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.forename: Robert L
authors.initials: RL
authors.lastname: Murphy
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Roland
authors.initials: R
authors.lastname: Tubiana
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Jose
authors.initials: J
authors.lastname: Gatell
authors.forename: Schlomo
authors.initials: S
authors.lastname: Staszewski
authors.forename: Norma
authors.initials: N
authors.lastname: Wincker
authors.forename: Lambert
authors.initials: L
authors.lastname: Assoumou
authors.forename: Raphaelle
authors.initials: R
authors.lastname: El-Habib
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Bruce
authors.initials: B
authors.lastname: Walker
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology / Q000627:therapeutic use*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007114:Immunization / Q000379:methods; D007115:Immunization Schedule; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines; C112734:AIDSVAX; D012367:RNA, Viral