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.

TitleAIDS 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.
Publication TypeJournal Article
Year of Publication2010
AuthorsSchooley RT, Spritzler J, Wang H, Lederman MM, Havlir D, Kuritzkes DR, Pollard R, Battaglia C, Robertson M, Mehrotra D, Casimiro D, Cox K, Schock B
Corporate AuthorsAIDS Clinical Trials Group 5197 Study Team
JournalJ Infect Dis
Volume202
Issue5
Pagination705-16
Date Published2010 Sep 1
ISSN1537-6613
KeywordsAdenoviridae, Adult, AIDS Vaccines, CD4-Positive T-Lymphocytes, Double-Blind Method, Female, Gene Products, gag, HIV Infections, HIV-1, Humans, Immunization, Interferon-gamma, Male, Treatment Outcome, Vaccines, DNA, Virus Replication
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.

DOI10.1086/655468
Alternate JournalJ. Infect. Dis.
PubMed ID20662716
PubMed Central IDPMC2916952
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