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.

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.

• Authors: Robert T Schooley, John Spritzler, Hongying Wang, Michael M Lederman, Diane Havlir, Daniel R Kuritzkes, Richard Pollard, Cathy Battaglia, Michael Robertson, Devan Mehrotra, Danilo Casimiro, Kara Cox, Barbara Schock, AIDS Clinical Trials Group 5197 Study Team
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 202 Issue 5 Pg. 705-16 (Sep 01 2010) ISSN: 1537-6613 [Electronic] United States
• PMID: 20662716 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

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