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

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 log₁₀ HIV-1 RNA load at the ATI set point and the time-averaged area under the curve served as coprimary 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 . The estimated P ≤.025 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) log₁₀ Pp.04 Pp.07 copies lower, respectively, in the vaccine arm than in the placebo arm. HIV-1 gag-specific CD4⁺ cells producing interferon-γ 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.