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.