title: AIDS clinical trials group 5197: a placebo-controlled trial of immunization of HIV-1-infected persons with a replication-deficient adenovirus type 5 vaccine expressing the HIV-1 core protein.
abstract: BACKGROUND
  Human immunodeficiency virus type 1 (HIV-1)-specific cellular immunity contributes to the control of HIV-1 replication. HIV-1-infected volunteers who were receiving antiretroviral therapy were given a replication-defective adenovirus type 5 HIV-1 gag vaccine in a randomized, blinded therapeutic vaccination study.
  
  
  METHODS
  HIV-1-infected vaccine or placebo recipients underwent analytical treatment interruption (ATI) for 16 weeks. The log(10) HIV-1 RNA load at the ATI set point and the time-averaged area under the curve served as co-primary end points. Immune responses were measured by intracellular cytokine staining and carboxyfluorescein succinimidyl ester dye dilution.
  
  
  RESULTS
  Vaccine benefit trends were seen for both primary end points, but they did not reach a prespecified significance level of P < or = 25. The estimated shifts in the time-averaged area under the curve and the ATI set point were 0.24 (P=.04, unadjusted) and 0.26 (P=.07, unadjusted) log(10) copies lower, respectively, in the vaccine arm than in the placebo arm. HIV-1 gag-specific CD4(+) cells producing interferon-gamma were an immunologic correlate of viral control.
  
  
  CONCLUSIONS
  The vaccine was generally safe and well tolerated. Despite a trend favoring viral suppression among vaccine recipients, differences in HIV-1 RNA levels did not meet the prespecified level of significance. Induction of HIV-1 gag-specific CD4 cells correlated with control of viral replication in vivo. Future immunogenicity studies should require a substantially higher immunogenicity threshold before an ATI is contemplated.
authors.affiliation: Div. of Infectious Diseases,University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. arsexton@ucsd.edu
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schooley
authors.forename: John
authors.initials: J
authors.lastname: Spritzler
authors.forename: Hongying
authors.initials: H
authors.lastname: Wang
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Diane
authors.initials: D
authors.lastname: Havlir
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.forename: Richard
authors.initials: R
authors.lastname: Pollard
authors.forename: Cathy
authors.initials: C
authors.lastname: Battaglia
authors.forename: Michael
authors.initials: M
authors.lastname: Robertson
authors.forename: Devan
authors.initials: D
authors.lastname: Mehrotra
authors.forename: Danilo
authors.initials: D
authors.lastname: Casimiro
authors.forename: Kara
authors.initials: K
authors.lastname: Cox
authors.forename: Barbara
authors.initials: B
authors.lastname: Schock
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D014779:Virus Replication
chemical_list: D016915:AIDS Vaccines; D015683:Gene Products, gag; D019444:Vaccines, DNA; D007371:Interferon-gamma