HIV vaccine trials in developing countries. The UNAIDS perspective.
Even though most people agree that a safe, effective, and available HIV preventive vaccine is needed, few agree on the characteristics of such a vaccine and how to proceed. The debate revolves around the uncertainties of the immunological correlates of protection, the antigenic significance of HIV genetic variability on vaccine-induced protection, and the biological variability of HIV and the meaning of animal protection experiments with experimental vaccines. The decision to move towards efficacy trials depends on feasibility, the science, and the vaccine. One important feasibility factor is availability of a well-characterized population with a high incidence of HIV infection, despite available interventions. A scientific factor to consider is HIV characterization (genetic variability, HIV subtypes). Current safety and immunogenicity data from phase I and II trials and ability of the vaccine to induce neutralizing antibodies and CTLs comprise some vaccine factors. Researchers have found high-risk populations willing to participate in phase III trials in Thailand. UNAIDS proposes a balanced approach strategy of conducting efficacy trials with vaccine candidates which have met minimal requirements while also conducting basic research to acquire more information on what is needed for a protective immune response. The efficacy trials may reveal some information related to such a response. Final decisions and responsibilities lie with national governments and institutions. UNAIDS is prepared to help countries in their decision making efforts. Extensive preparation and international collaboration and coordination are needed for phase III efficacy trials. Developing countries (e.g., Thailand) themselves must participate in HIV vaccine development, since most HIV infections are in these countries and these countries have the most to gain. Genetic variability of HIV and different co-factors and routes of HIV transmission indicate the need to conduct multiple efficacy trials in different areas worldwide.