[Letter to Daniel K. Inouye from Anthony S. Fauci]

3. What would be the cost of a Phase II/Phase III AIDS vaccine clinical trial?
The costs of conducting HIV vaccine efficacy trials is dependent upon the numbers of
subjects, the length of the study, and protocol design. General estimates for trials consisting
of 5,000 volunteers and conducted over a 3-5 year period range from $1.5 to $2.0 million per
annum, or $4.5 to $10.0 million per trial. It should be noted that the actual number of
subjects required for each trial will vary depending on factors discussed above (see No. 1);
thus, the 5,000 figure is provided for illustration only.
4. If in fact only one test can be successfully run in the United States and the cost of the test is
not a factor, is it better to wait until you can choose the best potential candidate from several
contenders or should the United States financially support human efficacy tests of safe,
immunogenic vaccines in other countries?
Because of the need for a large population of uninfected individuals at high risk for HIV
infection to do an vaccine efficacy trial in the U.S., the current scientific consensus is to wait
for a candidate(s) that shows outstanding promise in both early human aTnd animal studies
before proceeding with ohe or more trials. It is recognized, however, that one vaccine
candidate may not be optimal for all populations in this country or internationally, and that
multiple candidates may be necessary for different populations at a number of sites. In order
to maintain maximum flexibility to provide the best candidate HIV vaccines the greatest
opportunity for clinical evaluation, the NIAID/NIH has recently outlined plans to provide the
capabilities for conducting HIV vaccine trials both in the United States and in international
sites. A central tenet of this strategy is that the NIH will strive for maximum collaboration
with other international HIV vaccine programs, in efforts to maximize productivity and
eliminate duplication of effort. Thus, it is anticipated that HIV vaccine efficacy trials will be
conducted under the sponsorship of several collaborating organizations, including the W.H.O.
and the pharmaceutical industry.
ANIMAL MODELS
5.6.7. Given that human immunodeficiency virus (HIV) is a uniquely human germ, is it not likely
that testing for efficacy in chimpanzees could produce misleading information and actually
result in choosing the wrong vaccine to test in humans?
Can monkeys and chimpanzees be infected with the human AIDS virus, and if so, what
percentage of animals infected with HIV develop the same type of clinical disease seen by
human AIDS victims? What percentage of experimentally HIV infected non-human primates
die of AIDS?
I have been told that even the best animal models do not always forecast what will happen in
humans. For example, the small pox vaccine which eradicated small pox in humans produces
such deep ulcers in monkeys that had it first been tested on these animals it is likely it would
have been judged unfit for humans. Also, more recently, a genetically engineered vaccine for
malaria which achieved excellent results in protecting vaccinated rats from malaria proved to
be ineffective in humans. Why do you believe that an animal model will be more successful in
helping to find an effective AIDS vaccine?