HIV Vaccine Breakthroughs: Who Pays?

Anthony Canamucio In and outside his territories and dominions ... and with his far off neighbors, Priyadarsi has arranged for the medical treatment of man and beast. He has caused herbs, roots and fruits to be imported, wells to be dug and trees to be planted on the roadside for the enjoyment of men and animals. --Edits of Asoka, third century BC, inscribed on a rock in Girnar, Gujarat, India On occasion, an ethical consensus may be reached only to unravel as the question of "who pays" becomes a reality. This is precisely the issue facing the sponsors of HIV vaccine clinical trials in developing countries concerning the treatment of vaccine breakthroughs--individuals who become infected after immunization because the vaccine failed to protect them. Prior to the advent of potent antiretroviral therapy (ART), HIV vaccine trials offered an opportunity to study both the efficacy of an HIV vaccine and the potential to modify disease progression in the absence of therapy. The availability of zidovudine monotherapy in 1987 initiated a debate on the ethical requirement to use zidovudine for HIV vaccine breakthroughs. Once combination ART became the standard of care in developed countries, ethicists reasoned that this same standard of care, regardless of cost, should be provided for HIV vaccine breakthroughs. If this standard were applied for HIV vaccine trials, a substantial increase in the study size and duration would be required, because the endpoint of disease progression would be significantly delayed. Advances in HIV research have primarily benefited developed countries, as evidenced by a marked decline in new HIV infections and a decrease in HIV-related deaths.1 Two factors emerge as a result of these advances, which have a direct impact on the conduct of HIV clinical research. The first is that the population base required to evaluate new therapies has increased significantly, because new therapies must now be evaluated in the context of existing therapy. The second is that there is now a relatively low and stable incidence of new HIV infections and progression to AIDS, making it difficult to perform HIV vaccine trials in a timely and cost-effective manner in developed countries. Consequently, developing countries, with their large populations of HIV-infected or at-risk individuals, have become attractive alternative study sites. While an effective HIV vaccine is desperately needed by both developed and developing countries, the many benefits to developed countries, derived from the efficiency and economy of performing studies in developing countries, may require that developing countries receive compensatory benefits that may not be considered an ethical requirement in developed countries.2 The principle of distributive justice partially addresses this issue.3,4 However, in extremely resource-poor countries, proportionately greater benefits need be considered as well (proportionate justice). Some might argue that HIV infection occurring during the course of an HIV vaccine clinical trial is a result of failure of the study participant to adhere to prevention counseling and, therefore, no treatment is required. However, it can also be argued that clinical trial participants are recruited from populations at high risk for HIV infection; investigators have selected these sites precisely because a significant proportion of participants will become infected. Further, the efficacy of current HIV vaccines, if there is any, will fall far short of the 90% or more efficacy achieved by vaccines such as polio and measles.5,6 Unlike these infections, which are rarely fatal, HIV infection is invariably fatal. Finally, since ART and monitoring would be provided if the trial were performed in a developed country, it follows that treatment and monitoring for populations involved in studies in developing countries should also be provided. Who is ethically and/or legally responsible for assuming the cost for the treatment and monitoring? The general principle is that the sponsor(s) has ultimate responsibility for clinical research study costs, including direct and indirect costs, and those resulting from adverse events (vaccine breakthroughs might be considered adverse events). The sponsors would include the pharmaceutical or biotechnology company, National Institutes of Health, or the university. Debates among sponsoring parties as to who is obligated should not deter assignment of responsibility. Several mechanisms could be developed to fund the cost of ART and monitoring. A pool of funds, specific for ART and monitoring, could be derived from indirect and/or direct costs and administered by the sponsor or a third party. It is also possible that an insurance company, or insurance pool, could develop a limited liability policy to cover costs. Alternatively, a fund, derived from indirect or direct costs, could be established in each participating country to provide treatment and monitoring. These approaches could help resolve some of the difficulties facing developing countries that currently receive little to no indirect costs from research grants (an injustice in itself) and that lack private health insurance or uniform healthcare. Current recommendations concerning the initiation of treatment following HIV infection, suggest that ART could be delayed until specific viral load and/or CD4 count set points are reached. Since these may not be reached for 3 to 5 years after infection, treatment and monitoring are unlikely to commence for several years, and in many instances, not until after the vaccine trial has ended. Adequate time would be available for funds to accumulate and to develop a healthcare infrastructure. The lack of an established mechanism to administer a just solution should not be a deterrent to providing ART and monitoring for HIV vaccine breakthroughs. Individuals who enter our research "territory," including those participating in HIV vaccine trials, should not be abandoned once they become infected. Arthur J. Ammann, MD, is president of Global Strategies for HIV Prevention and clinical professor of pediatrics at the University of California, San Francisco, Medical Center. Global Strategies for HIV Prevention (www.globalstrategies.com) is a nonprofit organization, founded in 1998, dedicated to HIV prevention and responding to the needs of HIV infected women and children worldwide. References 1. H. Gayle, "An overview of the global HIV/AIDS epidemic, with a focus on the United States," Aids, 14(suppl 2):S8-17, 2000. 2. M. Barry, "Ethical considerations of human investigation in developing countries: the AIDS dilemma," N Engl J Med, 319:1083-6, 1988. 3. J. Rawls, Theory of Justice, Cambridge, Mass.: The Belknap Press of the Harvard University Press, 1999. 4. T. Beauchamp, J. Childress, Principles of Biomedical Ethics, 5th ed. New York: Oxford University Press, 2001. 5. J.P. Moore, D.R. Burton, "HIV-1 neutralizing antibodies: how full is the bottle?" Nat Med, 5:142-4, 1999. 6. K. Senior, "HIV-vaccine research takes one step forward. And one step back," Lancet, 359:235, 2001.

HIV Vaccine Breakthroughs: Who Pays?

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