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

J Infect Dis. 2010 Sep 1;202(5):705-16. doi: 10.1086/655468.

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.

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Vaccines* / administration & dosage
  • AIDS Vaccines* / adverse effects
  • AIDS Vaccines* / immunology
  • AIDS Vaccines* / therapeutic use
  • Adenoviridae / genetics*
  • Adenoviridae / metabolism
  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • Double-Blind Method
  • Female
  • Gene Products, gag / genetics
  • Gene Products, gag / metabolism*
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Immunization
  • Interferon-gamma / biosynthesis
  • Male
  • Treatment Outcome
  • Vaccines, DNA* / administration & dosage
  • Vaccines, DNA* / adverse effects
  • Vaccines, DNA* / immunology
  • Vaccines, DNA* / therapeutic use
  • Virus Replication

Substances

  • AIDS Vaccines
  • Gene Products, gag
  • Vaccines, DNA
  • Interferon-gamma

Grant support