HIV Vaccines - Accelerating the Development of Preventive HIV Vaccines for the World: Summary Report and Recommendations of an International Meeting

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Phase III studies (large-scale efficacy trials) have not yet been initiated but are expected to begin
in 1995. To prepare for these trials national governments and the WHO are developing the
necessary infrastructure in various countries. These efforts include: the characterization of HIV
sub-types found in possible trial populations, the training of investigators, the determination of the
seroincidence of HIV, general strengthening of the infrastructure and field management capacity
to undertake vaccine trials, and the development of the political support necessary for the
conduct of such trials.
Product development efforts have focused on a small number of the potential vaccine
approaches. The participants at the Bellagio meeting expressed concern about the lack of
attention being given to other approaches. A number of approaches are not currently being
"championed", including the two classical strategies, whole killed virus and live attenuated virus
(Table 1). These strategies, and in particular, the live attenuated virus approach, are perceived as
potentially less safe. However, a WHO expert committee that reviewed this issue in June 1993
concluded that the live attenuated approach "should be intensively explored". While ethical
principles must not be compromised, the participants noted that the high risk of infection in some
populations may justify the use of vaccine approaches that could potentially be less safe. For
example, a vaccine with a risk of a serious adverse reaction of 1 in 100,000 may be considered
better than no vaccine by a population with a high risk of infection, or better than an alternative
vaccine that has a lower risk of adverse reactions but is less efficacious. Live attenuated or whole
killed vaccines, if found to be efficacious, could represent viable cost-effective approaches under
some circumstances.
The meeting participants also noted that product development efforts have focused on the subtype of HIV found almost exclusively in North America and Europe - sub-type B (see Table 1).
Candidate vaccines representing sub-types prevalent in the developing world, and candidates
based on multiple sub-types are not being widely developed. While the immunological
importance of the different sub-types has not yet been determined, the current focus of
development activities on sub-type B could present problems when it comes to carrying out
efficacy trials and may result in substantial delays in the evaluation of candidate vaccines. In the
absence of more information on the immunological importance of the different sub-types of HIV, it
is important that vaccine trials are carried out with prototype vaccines based on the viral subtypes found in the trial site; otherwise, it will be difficult to evaluate the significance of a negative
result. There are, however, only a small number of population groups (primarily intravenous drug
users and individuals living in some resource-poor inner city areas) with high enough rates of
infection with sub-type B to carry out efficacy trials using realistic sample sizes. Some clinical
trials can almost certainly be done more effectively and expeditiously in developing country
populations with a high incidence of infection.
2.3 Financial resources
A review of recent activities in both the private and public sectors suggests that in 1993, less than
US$ 160 million was spent worldwide on HIV vaccine research and development (see Table 2).
This represents less than 10% of the total amount spent on HIV/AIDS-related research and
development. It is a fraction of the amount spent in 1992 on HIV prevention (US$ 1.3 billion in
developed and US$ 0.2 billion in developing countries) and on HIV-related health care (US$ 4.7
billion in developed and US$ 0.34 billion in developing countries), and a very small fraction of the