Moving forward on HIV vaccine trials and human rights
Dr. Joris Hemelaar
Final year graduate-entry medical student. Magdalen College, Oxford University. joris.hemelaar@medschool.ox.ac.uk
Last month a large-scale clinical trial of a candidate HIV vaccine started in South Africa.1 The four-year study plans to enrol 3000 HIV-negative sexually active men and women at five sites throughout South Africa, making it the largest African HIV vaccine trial to date. In South Africa, the trial is called Phambili, which means “moving forward” in the Xhosa language.
The study is a collaboration between the South African AIDS Vaccine Initiative (SAAVI) and the HIV Vaccine Trials Network (HVTN) in the United States, which is supported by the National Institute of Allergy and Infectious Diseases (NIAID). The vaccine was developed by Merck and consists of a weakened adenovirus containing three HIV genes. In previous smaller trials the vaccine was shown to be safe and stimulate HIV-specific cellular immune responses in more than half of the volunteers. The vaccine is currently also being tested in trials in the USA, Canada, South America, Australia and the Caribbean.
The objectives of the study are to determine whether the vaccine can prevent HIV infection in heterosexual men and women and whether it can reduce the level of viraemia should people get infected despite the vaccine. In addition, the study will shed light on the question whether the vaccine, which is based on the subtype B strain of HIV prevalent in the Americas and Europe, protects against infection by the C subtype prevalent in South Africa.
From a human rights perspective this trial raises several questions. Are the South African volunteers “guinea pigs” for the testing of vaccines designed by companies and governments from developed countries and intended for use in those countries? Will South African volunteers be subject to the same rules governing informed consent as their counterparts in the developed world? Will they have the same standard of care and treatment should they become infected during the course of the trial? And what is the legal framework governing these ethical and human rights issues? A number of national and international bodies have drawn up ethical guidelines for the conduct of medical research involving human beings.
Valid informed consent should be obtained from all volunteers.2-7 The HVTN model of informed consent recommends coverage of numerous issues, including details of trial procedures such as clinic visits, emphasis that the efficacy of the vaccine is unknown and protection against HIV must not be assumed, and explanation of the risks of study participation, including possible discrimination and stigma.2 Understanding of this information by the participant should be ascertained and informed consent obtained in a culturally sensitive and entirely voluntary fashion. It is unclear whether these goals can be achieved to the same extent in both developed countries and South Africa.
A contentious point is the level of care and treatment received by participants who become infected with HIV during the trial. The HVTN guidance states that participants have the right to “referral to available counselling, support, medical and treatment services if they become infected with HIV during the study.”2 Notably, the statement only talks about a right to “referral” and not about the provision of actual treatment. The “available…services” are likely to be very different for a volunteer in South Africa compared with one in the USA. Although highly active anti-retroviral therapy (HAART) is now becoming available in South Africa, coverage is still far from complete.
International guidelines for treatment provision differ markedly. UNAIDS guidance states that “the ideal is to provide the best proven therapy, and the minimum is to provide the highest level of care attainable in the host country.”3 This latter level of care should be agreed upon through a host/community/sponsor dialogue prior to initiation of a trial. However, the Nuffield Council on Bioethics recommends the level of care provided in the public health system in the country where the trial is conducted.4 Guidelines from the Council for International Organizations of Medical Sciences (CIOMS) say that there is no obligation but it would be morally praiseworthy to provide treatment for a condition that an experimental vaccine is designed to prevent.5 Therefore, with greatly varying guidance, the provision of treatment to trial participants is therefore largely left to the trial organisers’ discretion.
Another major area of concern is the post-trial obligation to provide a vaccine that proves efficacious. UNAIDS and CIOMS guidelines mandate provision of a proven efficacious and safe vaccine to trial participants who received placebo.3, 5 The Declaration of Helsinki mandates “access to the best proven…methods identified by the study or access to other appropriate care.”6 The Nuffield Council report merely states that researchers should endeavour to secure post-trial access to control group participants and that a decision whether or not such provision is possible should be taken before commencement of the trial.4
A further question is whether a successful product should be provided to the wider community or country where the trial was conducted. UNAIDS and CIOMS both indicate that a vaccine should be made available to other populations at risk of HIV infection.3, 5 The Nuffield Council only mentions that this should be considered.4 There is no agreed course of action regarding provision of the candidate vaccine of the current trial to the control group or wider South African community should the vaccine prove efficacious.
When governments are involved (through their research agencies) in the sponsoring or conducting HIV vaccine trials, they are also responsible for any abuses of human rights during the course of these trials. The internationally accepted ethical principles of research involving human beings contained within the various documents and guidelines should therefore form the basis for the protection of the human rights of trial participants in any part of the world. However, in the case of HIV vaccine trials, the guidelines often differ in their recommendations. Moreover, there is no legal obligation for any of these guidelines to be implemented and no mechanisms in place for their enforcement. It is time to draw up and enforce universal legally binding guidelines for the protection of human rights of volunteers in HIV vaccine trials.
References
1. HIV Vaccine Trials Network. Questions and answers: HVTN 503 vaccine trial, November 8, 2006. Available at: http://www.hvtn.org/faq/503/HVTN503FAQ_eng.pdf Accessed: 19 March 2007
2. HIV Vaccine Trials Network. Participants’ Bill of Rights and Responsibilities. Available at: http://www.hvtn.org/community/rights.html Accessed: 19 March 2007.
3. Joint United Nations Programme on HIV/AIDS (UNAIDS). Ethical Considerations in HIV Preventive Vaccine Research. Geneva: UNAIDS, 2000. Available at: http://data.unaids.org/Publications/IRC-pub01/jc072-ethicalcons_en.pdf Accessed: 19 March 2007.
4. Nuffield Council on Bioethics. The Ethics of Research Related to Healthcare in Developing Countries, 2002. Available at: http://www.nuffieldbioethics.org/go/ourwork/… Accessed: 19 March 2007.
5. Council for International Organizations of Medical Sciences (CIOMS). International Ethical Guidelines for Biomedical Research Involving Human Subjects, 1982, last updated in 2002. Available at: http://www.cioms.ch/frame_guidelines_nov_2002.htm Accessed: 19 March 2007.
6. WMA. Declaration of Helsinki, 1964, as last amended by the World Medical Association 55th General Assembly, Tokyo, Japan, 2004. Available at: http://www.wma.net/e/policy/b3.htm Accessed: 19 March 2007.
7. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report. Ethical Principles and Guidelines for the Protection of Human Subjects of Research, 1979. Available at: http://ohsr.od.nih.gov/guidelines/belmont.html Accessed: 19 March 2007.
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