Principles and Practices: The implementation of ethical guidelines for research on HIV Geneva, 2-3 June 2003 Ethical guidelines for HIV vaccines: Generic versus specific issues and the question of exceptionalism José Esparza WHO-UNAIDS HIV Vaccine Initiative Initiative for Vaccine Research

Why to develop specific guidelines for HIV vaccine research? HIV/AIDS research was the driving force for the development of ethical review activities in many developing countries. Vaccine research is specially sensitive because it involves the administration of biological products (experimental vaccines) to thousands (and eventually millions) of healthy people. The perception exists that... –Vaccine research is very profitable for scientists and industry (glory and money). –Vulnerable volunteers in developing countries are used to test dangerous products before the vaccine is used in industrialized countries. Need to ensure that vaccines tested in developing countries are made available in these countries.

An ethical disbalance on HIV/AIDS research? The bulk of biomedical research on HIV/AIDS has been done to develop antiretroviral drugs, which (thus far) have mostly benefited patients in industrialized countries. A safe, effective and affordable preventive vaccine is the best long term hope in developing countries, although not enough is being done to develop that vaccine (because of scientific, logistical, ethical and financial disincentives). According to the late Jonathan Mann, the “paralysis in AIDS vaccine development violates ethical principles and human rights” (1998)

The UNAIDS Guidance Document on “Ethical considerations in HIV preventive vaccine research” Regional consultations in 1998 (Brazil, Uganda, Thailand, Washington) 120 participants, including ethicists, lawyers, activists, social and biomedical scientists, etc. Plenary meeting in Geneva (1998) Extensive discussion (1999) Publication of the document in May Use and adaptation by countries

Some lessons learned Reaching consensus in several regional consultations is not equivalent to reaching global consensus (different regional realities). “Global” guidelines do not replace the need for decision making at the community and national level (guidelines can only offer guidance, and suggest standards and process for achieving standards). Dilemma between choosing between the “highest” and the “highest attainable” standards. Standards are moving targets.

UNAIDS 18 Guidance Points HIV vaccine development Vaccine availability Capacity building Research protocols and study populations Community participation Scientific and ethical review Vulnerable populations Clinical trial phases Potential harms Benefits Control group Informed consent Informed consent- special measures Risk.reduction interventions Monitoring informed consent and interventions Care and treatment Women Children

UNAIDS Guidance Point 16: Care and treatment (1) Care and treatment for HIV/AIFDS and its associated complications should be provided to participants in HIV preventive vaccine trials, with the ideal being to provide the best proven therapy (an established intervention), and the minimum to provide the highest level of care attainable in the host country in light of the circumstances listed below. A comprehensive care package should be agreed upon through a host/community/sponsor dialogue which reaches consensus prior to initiation of the trial, taking into consideration the following:

UNAIDS Guidance Point 16: Care and treatment (2) level of care and treatment available in the sponsor country highest level of care available in the host country highest level of treatment available in the host country, including the availability of antiretroviral therapy outside the research context in the host country availability of infrastructure to provide care and treatment in the context of the research potential duration and sustainability of care and treatment for the trial participant

Follow-up of guidance point 16 (and the question of exceptionalism) With expanded access to antiretroviral therapies globally, the issue of level of care for HIV vaccine volunteers is not longer “IF” but “HOW”. Standards and approaches proposed for vaccine trials should/would also be applicable to other AIDS prevention research. WHO-UNAIDS consultation (17-18 July 2003) –scientific, ethical, operational and financial considerations –vaccines, microbicides, behavioural interventions How (high) standards on HIV/AIDS research will influence standards for other research?