AN HIV Vaccine Trial in the Caribbean: The Haiti Site Experience

1. AN HIV Vaccine Trial in the Caribbean: The Haiti Site Experience S. Jean, J. Pape, M. Deschamps, A. Maxi, R. Verdier, T. Yamamoto, D. Fitzgerald, W. Johnson, P.Wright Centres GHESKIO, Port-au-Prince, Haiti Weill Medical College of Cornell University, New York, N.Y, USA Sponsored by: NIH

2. INTRODUCTION HIV Vaccine trials are a very sensitive topic worldwide, with a high level of Government scrutiny and press coverage. As a part of its contribution in the global effort to control the AIDS pandemic, GHESKIO Centers were the first Caribbean site to initiate HIV vaccine trial in March 2001. I am very happy to share with you this successful experience.

3. Plan of the Presentation • The Institution, GHESKIO Centers • Mission • Patient care providing • Training of Health Professionals • Implementation of Research • Site Preparation for HIV Vaccine Trials • Political commitment by the government • Community support • Capacity building

4. Plan of the Presentation (cond ’t) • The HVTN 026 Protocol • Objectives • Summary of the protocol • Results • The development of appropriate strategy to improve Informed Consent • Conclusion

6. The Institution: GHESKIO Centers • Non governmental organization (NGO) (1982) • Mission : services, research, and training • Collaboration • Local Institutions : Haitian Ministry of Health and Population, Haitian Medical Association and 114 other institutions • International Institutions: American Universities : Cornell (1982), Vanderbilt (1989), Johns Hopkins, Harvard (1991), Hastings Center (1999) French Institutions : Institut Alfred Fournier (1989), Institut Pasteur (1999), Université d’Amiens (1999)

7. Voluntary Counseling and testing Centers (VCT) with integrated services As VCT GHESKIO Centers offer: • The opportunity to intervene in both prevention and care • The possibility to recruit volunteers for HIV Vaccine trials

8. GHESKIO Centers Profile • GHESKIO Centers are the main VCT center in Haiti. In 2003, over 21,279 individuals were tested for HIV. ~ 50% are aged 18-50 years, of which ~ 70% are HIV negative, and candidates for vaccine trials. • A mean of 500 persons a day come for health care • Training: as of November 2003, 6799 health care providers were trained

9. Implementation of Research • Since its inception in 1982, GHESKIO has emerged as a national and international leader in the fight against AIDS. Through its mission to provide patient care and train health professionals, GHESKIO developed a mutual trust with the community, which permitted implementation of research. As a part of its contribution in the global effort to control the pandemic, GHESKIO Centers was the first Caribbean site to initiate HIV vaccine trial in March 2001.

10. PREPARATORY PHASE FOR HIVVACCINE TRIAL (1991-2001) • Political Commitment by the government • Community Support • Ethics Support • Competency of the staff • Capacity building • Evaluation of potential study population Supported by NIH PAVE, HIVNET, HVTN, AITRP

11. HVTN 026 Haiti participated with Trinidad, Brazil, Peru in a Multisite Phase II Clinical Vaccine Trial to evaluate two candidate vaccines the ALVAC 1452 HIV -1 (Aventis Pasteur) and rgp120 (Vaxgen)

12. OBJECTIVES • To confirm the safety and to define the immunogenicity of both products in populations represented by different genetic pools and other host factors, such as nutritional status, that may impact on responses to the vaccines • To establish the capability of testing HIV vaccines in international sites to prepare for larger scale trials

13. Summary of the protocol • 40 healthy volunteers (18 to 60 years old) in each site, were randomly assigned in 3 groups to receive: • 1- Both products (ALVAC, rgp120) n = 15 • 2 -One product ( ALVAC alone) n = 15 • 3 - Placebos n = 10 • They were assigned to receive 4 doses in 6 months at 0, 1, 3, 6 months

14. Summary of the protocol (cont’d) • Duration of the follow - up: 18 mo post enrollment • End points were: • Safety measurements • Immunogenicity measurements • Detection of intercurrent infection

15. Strategy to improve informed Consent • Sensitization • Willingness Questionnaire • Educational sessions • Evaluation of the comprehension before signing the Consent Form • Evaluation of the level of motivation before enrollment

16. Sensitization

19. Willingness to Participate • During post-test counseling, sensitization is done on an individual basis by a social worker. Interested healthy HIV negative adults 18 – 60 years old are referred to the HIV vaccine Unit for a “Willingness Questionnaire”

20. Willingness Questionnaire • Knowledge about vaccines in general is tested • Information about HIV vaccine trials worldwide is given • Questions are asked, for example: “Would you be willing to participate knowing that your HIV test may become positive?” • In 2001, of 2,060 interviewed, 78% were interested in participating.

21. Obtaining Informed Consent • The procedure used in informed consent had been designed to educate the subject population in terms that they could understand all aspects of the protocol before signing the consent form. • The consent form has been translated into Creole • An illustrated booklet has been written, in which standardized questions dealing with key issues of the protocol have been debated.

22. Educational Booklet

24. Obtaining Informed Consent • At least, three (3) educational sessions of one (1) hour each were provided to each volunteer • The comprehension and the level of motivation was evaluated by a psychologist not involved in the educational sessions. • From 680 volunteers that took part in the pre-screening process (026 protocol), 244 were eligible following clinical & laboratory screening • 81/244 signed the informed consent form

25. Enrollment • Before enrollment, a second evaluation was performed by the P.I., Co-P.I. and the ethics liaison person to assure that volunteers had really understood the study and were motivated to participate. • From the 81 subjects who signed the consent form, 50 passed all stages including the second evaluation • 40 were enrolled in the 026 protocol with 100% retention

26. RESULTS • The products were proven to be safe, well tolerated • Follow up : 100% of retention • No HIV infection • At the end of the study 85% (12/14) of those who received both products had antibodies induced by the vaccines (positive ELISA by Abbott)

27. RESULTS (cont’d) • 73% (11/15) of those who received the ALVAC alone had antibodies induced (positive ELISA by Abbott) • Further immunogenicity data are not available yet

28. Conclusion • With sufficient time and care it is possible to obtain proper informed consent from a population with limited formal education. We were able to obtain 100% of retention after completion of the study. In the group inoculated with candidate vaccines, HIV antibodies were detected with conventional HIV screening tests in a majority of the participants.

29. Conclusion (cont’d) • This information is important to give to participants in an HIV vaccine trial to alert them to the potential for stigmatization and social harms. • The clinical and laboratory capacity built for HIV Vaccine Trials has strengthened patient care and other research and training activities at GHESKIO.

30. Conclusion (cont’d) Based on this successful experience, Haiti is selected to conduct other HIV vaccine trials. Our site is now activated for the evaluation of the new Merck vaccine and will be ready for a Phase III trial.