Adenovirus vaccine favored modest viral suppression of HIV-1 RNA

Schooley RT. J Infect Dis. 2010;202:705-716.

Patients with HIV-1 receiving an adenovirus vaccine showed modest — but not statistically significant — viral suppression, according to study results.

Researchers from several institutions in the United States worked from the premise that HIV-1–specific cellular immunity contributes to the control of HIV replication. They administered a replication-defective adenovirus type 5 HIV-1 gag vaccine to patients with HIV on antiretroviral therapy. The trial was conducted from August 2004 to June 2006.

There were 73 participants randomly assigned the vaccine and 37 assigned placebo. All participants underwent analytical treatment interruption for 16 weeks.

There were two primary endpoints: the log₁₀ HIV-1 RNA load at the analytical treatment interruption set point and the time-averaged area under the curve, according to the results. The researchers measured immune responses using intracellular cytokine staining and carboxyfluorescein succinimidyl ester dye dilution.

A prespecified statistical significance level of P<.025 was set for both primary endpoints. Although benefit trends for the vaccine were observed for both endpoints, neither trend reached this level of significance.

The estimated shift in the time-averaged area under the curve in the treatment arm compared with the placebo arm was 0.24 (P=.04). The estimated shift in the analytical treatment interruption set point was 0.26 log₁₀ copies lower in the treatment arm compared with the placebo arm (P=.07).

“Although the vaccine stimulated HIV-1–specific cellular immune responses, the effect of the vaccine on viral rebound kinetics during the [analytical treatment interruption] was modest at best,” the researchers wrote.

Vaccination resulted in a modest increase in the frequency of HIV-1 gag-directed CD8 cells producing interferon-gamma. However, the vaccine was more frequently associated with increased frequencies of CD4 cells producing gag-specific interferon-gamma.

“Proportions of CD4 cells producing gag-specific interferon-gamma strongly correlated with the control of viral replication in the analytical treatment interruption,” the researchers wrote. “Although HIV-1–specific cytolytic activity by CD4 effector cells has been reported, our study does not establish whether these cells have a direct effect on infected cells, are a surrogate of immune responsiveness, or augment HIV-1–specific cellular immunity indirectly through other cellular effectors.”

The vaccine was generally safe and well tolerated, according to the results.

The researchers suggested that “future immunogenicity studies should require a substantially higher immunogenicity threshold before an [analytical treatment interruption] is contemplated.”