Great Expectations Dashed: Results of another HIV Vaccine Study Disappoint
ABSTRACT & COMMENTARY
By Dean L. Winslow, MD, FACP, FIDSA
Clinical Professor of Medicine and Pediatrics Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Associate Editor of Infectious Disease Alert
Dr. Winslow is a consultant for Siemens Diagnostic.
SYNOPSIS: A promising HIV vaccine trial was halted due to evidence of infection and no differences between vaccine and placebo recipients in viral load set point.
SOURCE: Hammer SM, et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med 2013; 369: 2083-92.
In a large multi-site study 2504 men (or transgender women) who have sex with men were randomized to receive DNA/rAd5 vaccine or placebo. HIV acquisition was assessed from week 28 as was the HIV RNA set point at 10-20 weeks after diagnosis of HIV infection. The study was halted by the data and safety monitoring board after interim analysis showed that week 28+ infection had been diagnosed in 27 patients in the vaccine group and 21 in the placebo group. There were no differences between vaccine and placebo recipients in viral load set point.
The results of this trial are very disappointing. This particular vaccine was one of the most hopeful candidates that have been developed over the past 20 years and employed a recombinant DNA "prime" (6 closed circular plasmids which individually expressed HIV-1 clade B Gag, Pol, and Nef as well as Env proteins from clades A, B, and C) followed by a "boost" using four recombinant Adenovirus 5 vectors expressing an HIV-1 clade B Gag-Pol fusion protein and Env glycoproteins from clades A, B, and C. In earlier studies this "prime-boost" vaccine elicited extremely robust cellular and humoral immune responses in animals and human subjects. Since these preliminary results were so promising it was anticipated that this new vaccine would have some efficacy despite the largely negative efficacy results seen in clinical trials of recombinant HIV-1 Env or Gag proteins or Adenovirus vector vaccines.
I remember participating in a meeting held in Bethesda in about 1990 at which scientists discussed the future of HIV vaccine development. There was a lot of hope at that time that an effective HIV vaccine could be developed in just a few years and would eventually obviate the need for antiretroviral therapy. However, I also remember at that same meeting Dr. William Haseltine standing up (and to the obvious chagrin of Dr. Fauci) proceeding to tell all of us that, "Development of an HIV vaccine is a pretty big stretch since we don't understand the first thing about immunity to retroviruses or even if immunity is possible!"
As a congenital optimist, I'm still hopeful that we will eventually develop an efficacious HIV vaccine—but enough of a realist to not predict a short timeframe for that to occur.