HIV Vaccine Research at CRT-DST/AIDS Artur Olhovetchi Kalichman

1. HIV Vaccine Research at CRT-DST/AIDS Artur Olhovetchi Kalichman

2. CRT DST/AIDS • The STD/Aids Reference and Training Center belongs to the São Paulo State Health Department and it is responsible for the Coordination of the STD/Aids Program in the State. The CRT-DST/AIDS is also responsible for inpatient and outpatient care for HIV infection and other STDs. • The CRT-DST/AIDS also performs clinical research to develop new ARV drugs for the treatment of PLHA and HIV preventive vaccines. • The HIV Vaccine Research Unit of the CRT-DST/AIDS starts its activities in 2001 as a member of the HIV Vaccine Trial Network (HVTN).

3. DAIDS Sponsored Networks (parcial / 12 of 23) AIEDRP Programa de Pesquisas sobre Infecção Aguda e Doença Precoce AACTG Grupo de Ensaios Clínicos sobre AIDS em Adultos CFAR Centros para Pesquisa sobre AIDS PACTG Grupo de Ensaios Clínicos sobre AIDS Pediátrico CPCRA Programa Comunitário de Pesquisas Clínicas sobre AIDS CIPRA Programa Internacional Extenso de Pesquisas sobre AIDS HPTN Rede de Ensaios Clínicos de Prevenção contra o HIV HVTN HIV Vaccine Trial Network MACS Estudo Multicêntrico de Coortes com AIDS ESPRIT Avaliação da Proleuquina Subcutânea em um Ensaio Clínico Aleatorizado Internacional WITS Estudo de Transmissão em Mulheres e Lactentes NCDDG Grupos Nacionais de Descoberta Cooperativa de Drogas

4. HVTUs Statistical and Data Management Center (SCHARP) Fred Hutchinson Cancer Research Center Core Operations Center Fred Hutchinson Cancer Research Center Laboratories *Duke University *California Department of Public Health Sciences *Fred Hutchinson Cancer Research Center *Nat’l Institute for Communicable Diseases

5. HVTN Clinical Trial Sites Rochester, NY New York, NY Providence, RI *Chicago, IL Sites for current HVTN trials *Philadelphia, PA St. Louis, MO Sites for future HVTN trials Seattle, WA * Joined the HVTN since 1999 Boston, MA San Francisco, CA Baltimore, MD Pune, India Washington, DC Nashville, TN Birmingham, AL Nanning, China Port-au-Prince, Haiti *San Juan, Puerto Rico Chiang Mai, Thailand *Kingston, Jamaica Kunming, China * Santo Domingo, Dominican Republic *Blantyre, Malawi *Orkney, South Africa *Gaborone, Botswana Port of Spain, Trinidad & Tobago Rio de Janeiro, Brazil *Soweto, South Africa *Sao Paulo, Brazil *Iquitos, Peru Lima, Peru * Durban, South Africa * Cape Town, South Africa Updated on 12/14/04

6. CORE Community Education Research Team • - Community Liason • - Recruitment • Retention Community Advisory Board Protocol and Consent form assessments Community Education Advise on Recruitment & Retention Representative voice for participants

7. Research Team • Unit Coordination : Clinic Coordination, Data Management and Quality Control, Legal and Regulatory issues from Brasil and USA, SOP development, Staff Training, Pharmacist (responsible for receiving, storage, control and preparation of the investigational products). • Field Team: Physicians, nurses, counselors, receptionist and Phlebotomists.

8. Legal and Regulatory Aspects • CEP/CONEP: The CRT-DST/Aids has its own IRB since 1998. Our IRB is responsible for the assessment of our protocols and for send it to CONEP for their assessment • CIBio/CTNBio: The local Biohazard Committee of the Instituto Adolfo Lutz is responsible for the assessment of our protocols and for send it to CTNBio for their assessment • ANVISA: To prepare the paperwork to obtain the permit for importing the product and perform the trial in the country according with the vaccine developer • HVTN/DAIDS/FDA: To comply with all legal and regulatory research legislation from the USA

9. Vaccine Trials CRT DST/AIDS Feasibility Study January 2003 to March 2005 Heterosexual coorte Participants- 211 men and women Protocol 050 Follow up Period (Year 3) Vector: Adenovirus type 5 Phase 1: Safety and Immunological response Participants: 18 to 50 years HIV negative and healthy Enrolled: 19 participants Begin: 2004

10. Vaccine Trials CRT DST/AIDS Protocol 055Follow up Period (month 7) Phase I: Safety and Immunological response Vector: MVA and FPV Participants: 18 to 24 years HIV negative and healthy Enrolled: 21 participants Begin: 2006 Protocolo 204Recruitment: begin in August 2006 Phase II A – Safety and Immunological response Product: multiclade HIV-1 DNA plasmid vaccine followed by a multiclade recombinant adenoviral vector HIV-1 vacccine boost Participants: 18 to 45 years, HIV negative and healthy Enrolled: 4 (untill 30 sep 2006) Target: 12 participants

11. Vaccine Trials CRT DST/AIDS • Protocolo 502 • Recruitment: begin in August 2006 • Phase II B – Safety, Immunological response and efficacy • Vector: Adenovirus type 5 • Participants: 18 to 45 years • Enrolled: 1 participant • Target: 65 45 men 20 women • Protocolo 063 • Approved for CEP, CONEP • ANVISA and CTNBio: under assessment • Recruitment: November 2006 • Phase I – Safety and Immunological response • Product: HIV-1 gag DNA vaccine alone or with IL-15 DNA, boosted with HIV-1 gag DNA + IL‑15 DNA, HIV CTL multiepitope peptide vaccine, or HIV-1 gag DNA + IL-12 DNA • Participants: 18 to 50 years • Participants: 12

12. CHALLENGES • Policy: • To establish a governmental policy for the participation of Brazil in international vaccine research networks and multilateral initiative. • This policy should provide the conditions to support technological development in the field and future access to the vaccine. • Regulatory and legal: • To reconcile different research legislations • To guarantee that the Brazilian legislations on research are obeyed • To guarantee that the time for approval process in the country do not compromise the beginning of the protocols at the same pace that • the other participants countries.

13. E-mail artur@crt.saude.sp.gov.br Home page www.crt.saude.sp.gov.br/vacinas