Ingrid Callies Legal Counsel in charge of ethics October 5, 2006

1. The French National Agency for Research on Aids and Viral Hepatitis – Clinical Research Legislation: A French Experience Ingrid Callies Legal Counsel in charge of ethics October 5, 2006

2. The ANRS • The ANRS is the French National Agency for Research on Aids and Viral Hepatitis. • The ANRS is a public agency, financed by the French Government, with a yearly budget of 45 million euros. • The ANRS funds research programs, sponsors clinical trials and award grandts after peer review of research proposals.

3. Introduction: The ANRS and Research on HIV Vaccines • For over ten years the ANRS has been committed to an original research program on HIV vaccines, combining basic science and clinical research. Between 10 and 20% of its budget is dedicated to the preventive vaccine research effort. • In addition, the ANRS is sponsoring clinical trials taking place in a therapeutic vaccine approach, on HIV seropositive patients.

4. Towards a Phase III Trial • The ANRS is one of the main international players in the search for a vaccine against HIV/AIDS. The Agency is conducting: • A program to evaluate immunogenic combinations in humans so as to set up a phase III trial within the next three to five years. This research is being pursued in collaboration with industrial companies and international partners, notably the National Institutes of Health (NIH). • Fundamental research on new approaches to a vaccine.

5. The Network of Volunteers • The setting-up of vaccine trials is contingent upon recruitment of suitable volunteers in whom the candidate vaccines are evaluated. • 1992: setting-up of a multidisciplinary committee to select candidates composed of ANRS representatives, clinicians and psychiatrists/psychologists. • Volunteers: 1) must be seronegative, 2) not exposed to risks of contamination, and 3) must understand and accept the risks associated with the research.

6. The Main Risks Taken into Account by the Volunteer Selection Procedure • A biological risk: the vaccine preparations tested may induce the production of antibodies which, in case of contact with HIV, facilitate contamination. • A behavioral risk: a volunteer who believes him/herself to be unduly protected by a candidate vaccine could adopt behaviors that heighten the risk of HIV contamination. • A psychological pressure: Participants in vaccine trials may produce anti-HIV antibodies. They are in a situation of « pseudo-seropositivity » or « seropositivity without the virus ». A screening test may be positive even though they are not carrying the virus. • A social pressure: The situation of pseudo-seropositivity may prove problematical in certain situations (crossing the borders of certain countries, obtaining insurance when applying for a loan…).

7. For Each New Trial :The Enrolment of Subjects in an ANRS Clinical Trial • At the ANRS, the protocols for any new clinical trial are discussed in depth by specialists’ committees. In each of these committees NGO representatives are present. The ANRS has a long standing collaboration with NGOs representing HIV-positive patients. • In addition to this review, the protocol, the information document and the consent form are reviewed and amended by NGO representatives. The purpose of this review is for the information to be understood by the patients and volunteers enrolled in one of our trials. • The volunteers contacted by the ANRS, as well as patients meeting the inclusion criteria are informed by the investigator of the objectives, risks and benefits of the trial and ask to sign a consent form.

8. Research in the Developing World Research in the developing countries is one of the priorities of the ANRS. Its action is sustained through research sites in Africa (Ivory Coast, Senegal, Burkina Faso, Cameroon), Asia (Cambodia, Vietnam) and Brazil, and is based on North/South team partnerships. The first ANRS site for research on viral hepatitis has been set up in Egypt. The research is conducted in accord with the ANRS’ charter of ethics in developing countries. The charter embodies three major principles: • The notion of a North/South partnership in all sectors; • Increased protection of people participating in research in developing countries; • The medical treatment of patients

9. Research in Developing Countries • 200 research projects funded since 1996 About 30 clinical trials (evaluation of ARV regimens, male circumcision…) • Cohorts 1) Long term follow up of patients under ART in Senegal (10 years of FU, N= 400) • Incident cohort of sex workers in Burkina faso (10 years of FU; N=600 ) • Natural history before ART initiation in patients with known date of HIV contamination in Ivory Coast (N= 660)

10. Site Strategy » : North / South partnership • Bilateral cooperative agreement • North and South scientific coordination • Multidisciplinary programs • Research Units implemented in public health structures • Long term funding: infrastructures, personal, equipment (transfer to the host country)) • Restitution of research results: annual ANRS scientific workhops (Authorities ++)