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Brazilian Ministry of HealthOswaldo Cruz Foundation
Oswaldo Cruz Institute
Mariza G. MorgadoLab. AIDS & Molecular Immunology
HIV Vaccine Research: Ethical and Regulatory IssuesPN-DST/AIDS – Brazilian Ministry of Health
Brasília – Out 2006
Brazilian Experiences in Collaborative and Preventive Multicentric Studies – FIOCRUZ
Objective: To obtain information on genetic and antigenic variation of HIV and its possible implications for vaccine development
Primary laboratories – Brazil, Rwanda, Thailand and Uganda
Secondary International laboratories for: Standardized virus isolation – repositoryGenetic subtyping – PCR gag fingerprint, HMA, V3 loop and env DNA sequencingBiological and immunological characterization - peptide binding EIA, CD4/gp120 blocking antibodies, in vitro replication characteristics and cross-neutralization assays
WHO-Global Programme on AIDS
Network for HIV Isolation and characterization
Brazilian Network of HIV Isolation and Characterization
Objective: To establish a Brazilian surveillance program to monitor the genetic and antigenic variation of HIV and its possible implications for vaccine development
Identification of potential participants;Organization of local seminars for protocol definition and implementation;Submission to WHO and PN-DST/AIDS funding;Organization of local “International Workshop Trainings”;In-country and international personnel trainings;Elaboration and conduction of scientific projects
Major strategies
(1993)
0
5
10
15
20
25
30
35
40
92-93 94-95 96-97 98-99 00-01 02-03 04-05
For.
Braz.
No.
of
papers
Source: PubMed – Key words: HIV and Brazil* Papers including HMA, DNA sequencing, RFLP, Neutralizing antibodies, peptide ELISA, ELISPOT, CMI
(N=106) (N=120) (N=242)(N=189) (N=194) (N=285)(N=113)
Medline available scientific publications 1992-2005
B, F, B/F
B, F, B/F, C, D, A,CRF02_AG, CRF28_BF, CRF_29BF
C, B, B/C, F, B/F, A
B, F, B/F
B, F, B/F, C
Molecular epidemiology of HIV-1 in BrazilMolecular epidemiology of HIV-1 in Brazil
Updated 2006
Rio de Janeiro, RJ
Belo Horizonte, MG
São Paulo,SP
Porto Alegre, RS
NICHD/HPTN 040
PHASE III RAMDOMIZED TRIAL OF THE SAFETY AND EFFICACY OF THREE NEONATAL ANTIRETROVIRAL
REGIMENS FOR PREVENTION OF INTRAPARTUM HIV-1 TRANSMISSION
HPTN 052
A RANDOMIZED TRIAL TO EVALUATE THE EFFECTIVENESS OF HIV PRIMARY CARE VERSUS HIV
PRIMARY CARE PLUS ANTIRETROVIRAL THERAPY TO PREVENT THE SEXUAL TRANSMISSION OF HIV-1
IN SERODISCORDANT COUPLES
Clinical Research - Brazilian HPTN Protocols
NICHD/HPTN 040NICHD/HPTN 040/HPTN052
BB
FF
CC
BC
BF
CBF
Morgado et al.2004 CROI
*
* RJ (n=39)
3%10% 87%
PoA (n=64)61%
25%11% 3%
HIV-1 subtype infection among HIV-1 subtype infection among pregnant women from Rio de pregnant women from Rio de
Janeiro, RJ, and Porto Alegre, RSJaneiro, RJ, and Porto Alegre, RS
RJ N=3,6891.35% of seropositive women (49)
PoA N=1,5246,3% of eropositive women (99)
(env & pol)(env & pol)
Good Laboratory Practices
Biosafety rules
Ethical Issues
Regulatory Issues
Major requirements for project participation
Central Laboratory
ldo Cruz Foundation)
HSE and HGNIRio de Janeiro, RJ
Plasma, blood cell pelletsand cryopreseved mononuclear cells
UFSPSão Paulo, SP
UFMGBelo Horizonte, MG
HC, HF, HSCPorto Alegre, RS
FIOCRUZ, RJ Study CoordinationData ManegementCentral Laboratory
NICHD-HPTN040 – Strategyshipping, storage and testing of biological samples
Repository RNA and DNA assays
Plasma, blood cell pelletsand cryopreseved mononuclear cells
Plasma, blood cell pelletsand cryopreseved mononuclear cells
Plasma, blood cell pelletsand cryopreseved mononuclear cells
Transport of clinical specimens
Results
Results
Transport of clinical specimens
ldo Cruz Foundation)
Hosp. Geral de Nova Iguacu Sample processing
Sample storageLDMS
CD4 counts
Hospital dos Servidores
*Reference of Genotyping also for the following centers:• Hospital Conceição, RS• IMPACTA, Lima, Peru
FIOCRUZ, RJ
Sample processingSample storage/LDMS
RNA assayCD4 counts
Genotyping*Hematol./Biochem/Immunol/Microbiol
Shipping & Training
Sample processingSample storage
LDMS
Clinical specimens Clinical specimens
Results
Johns HopkinsCentral Lab
HPTN052 – Strategyshipping, storage and testing of biological samples
Laboratory proceduresINMETRO NIT-DICLA 083 / ISO-IEC 15189SOPs
Internal and external controlsData registerData storage and controlResults
Sample processing and storage in biosafety conditions
Biological repository maintenance Cryopreserved mononuclear cells
PlasmaSeraBlood cell pellets
* RESOLUÇÃO N o 347, DE 13 DE JANEIRO DE 2005
National and international laboratory certifications
UKNEQAS (England)– Immunophenotyping
Virology Quality Assessment Program (USA) – DNA PCR; RT-PCR; Genotyping
Immunology Quality Assessment Program – PBMC cryopreservation
College of American Pathologists (USA) – CBC, serology, etc
Brazilian AIDS Program – immunophenotyping, VL and Genotyping
Major ethical and regulatory issues
Timeline to get the protocols approved.
Concerns about the storage of biological samples for further studies.
Timeline to prepare the documents (IL) and have them accepted for drug and reagent reception
Timeline to prepare the documents and have them accepted for importation and/or customs clearance of biological panels for laboratory proficiency tests.
Constant modifications in documentation required for shipping and/or clearance of drugs, reagents, and biological materials, including proficiency panels.