Panel to Review GP160 Vaccine Candidate: Report of the Meeting

Large-scale population considerations. Questions of how best
to move ahead with HIV vaccines go beyond purely scientific
issues, pointed out Mr. Mark Harrington, who is from the
Treatment Action Group in New York, New York. Hundreds of HIVinfected (or at-risk) individuals are "eager to enroll" in
clinical trials to test vaccines or other potential therapeutic
products, he said, referring primarily to populations of gay men
with high HIV infection levels and keen awareness of AIDS
research developments and needs.
A dozen AIDS organizations recently developed a consensus
statement calling for a "large randomized comparative trial in
which entry criteria are broad [and] data collection is
simplified," Mr. Harrington said. The group recommends that the
clinical trial test gpl60 and "any other appropriate vaccine
candidate that provides clinical benefits to people with HIV
disease." The group also calls for an early start for this trial,
urging that the candidate products for testing be identified by
mid January 1993.
Dr. Susan Ellenberg, Chief of the Biostatistics Research
Branch at NIAID, outlined key parameters for planning such a
large-scale, multiproduct vaccine trial for a HIV-infected
population. Although the trial needs to include placebo controls
for the vaccine, it needs also to accommodate the medical needs
of participants, meaning that appropriate and changing use of
therapeutic products --and the impact on the study results--has
to be taken into consideration as the trial progresses.
Such a trial could be expected to run for three to six
years, and it could require 14,000 patients if it runs the full
six years, but up to 30,000 patients if results were needed
within three years. With such large numbers, it will need to be
"simple" in design, and open virtually to anyone infected with
HIV who wants to participate. The relative merits of using a
surrogate end point, such as CD4 levels in serum, instead of
purely clinical end points also need to be carefully evaluated,
Dr. Ellenberg and others noted. However, she added, modest
effects on surrogate markers will "not be adequate" for assessing
efficacy of the vaccines being evaluated.
Dr. Salim Yusuf of McMaster University and Hamilton General
Hospital in Hamilton, Ontario, Canada, pointed out that past
efforts to conduct large, simple vaccine trials as well as
therapeutic agent efficacy-and-prevention trials (in cardiology,
particularly) have proved successful on several occasions. In the
polio vaccine case, the initial product under test was not the
one eventually put into widest use; nonetheless, the trial helped
prove the concept and therefore lead to the end product.
Other large-scale clinical trials conducted throughout the
world have provided useful answers about new products, suggesting
that much could be gained from testing AIDS vaccines in this
manner. Moreover, if multiple products were tested
simultaneously, it could provide additionally useful information
about additive and synergistic effects, which may prove highly
valuable when using these products to combat HIV infections.