Evaluation of Genetic Markers as Explanations for the Observed Differences in Disease Progression in HIV+ Youth
This protocol is a study of HIV+ young people who were identified as having certain HIV-1 specific T-cell responses and genetic markers while previously enrolled in the 5-year longitudinal adolescent study, "REACH." Blood samples will be collected, a medical and medication history and physical examination will be performed every 6 months for a total of 2 years.
|Study Design:||Observational Model: Cohort|
|Official Title:||Evaluation of HIV-Specific CD8+ T-Cell Responses and Escape Mutations as Explanations for the Observed Differences in Disease Progression Conferred by HLA Class I Alleles|
- Demonstrate that few CTL escape mutations occur in HIV-1 specific CD8+ T cell epitopes that are HLA-B*27 and B*57 restricted, when compared to those restricted by HLA-B*35 and B*53. [ Time Frame: 96 Weeks ] [ Designated as safety issue: No ]Demonstrate that few CTL escape mutations occur in HIV-1 specific CD8+ T cell epitopes that are HLA-B*27 and B*57 restricted, when compared to those restricted by HLA-B*35 and B*53.
- Demonstrate that CD8+ T cells have a high functional avidity to HLA-B*27 and B*57 bound epitopes when compared to those responding to HLA-B*35 and B*53 bound epitopes. [ Time Frame: 96 Weeks ] [ Designated as safety issue: No ]Demonstrate that CD8+ T cells have a high functional avidity to HLA-B*27 and B*57 bound epitopes when compared to those responding to HLA-B*35 and B*53 bound epitopes.
Biospecimen Retention: Samples Without DNA
Biomedical HIV-1 related data and samples are available for the time the subjects were enrolled in REACH. HIV-1 genotyping will certainly be possible from these retrospective samples and the stored PBMCs will be evaluated for usefulness in the HIV-1 specific assays. Prospectively, samples will be collected every six months over a two-year period to evaluate both HIV-1 specific CD8+ T cell responses and the dominant HIV-1 genotype longitudinally.
|Study Start Date:||December 2002|
|Study Completion Date:||September 2005|
|Primary Completion Date:||September 2005 (Final data collection date for primary outcome measure)|
Numerous studies have demonstrated an association between HLA class I genotypes with differing progression to AIDS in individuals who are followed after being off antiretroviral therapy. These studies do not always associate the same HLA class I alleles with the risks of HIV-1 disease progression; however they consistently demonstrated that HLA-B*35 and B*53 portend a bad outcome compared to the better outcome observed in HLA-B*27 and B*57 carriers. Despite this information, very little data exists to explain the mechanism of this association.
This longitudinal study will look at the HIV-1 specific CD8+ T-cell responses and the dominant HIV-1 genotype among individuals identified as HLA-B*27, B*35, B*53 and B*57 positive through studies done in collaboration with the REACH project.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00107029
|United States, California|
|Children's Hospital of Los Angeles|
|Los Angeles, California, United States, 90027|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, Florida|
|Children's Diagnostic and Treatment Center|
|Ft. Lauderdale, Florida, United States, 33101|
|University of Miami-Jackson Memorial Medical Center|
|Miami, Florida, United States, 33101|
|United States, Illinois|
|Cook County Children's Hospital|
|Chicago, Illinois, United States, 60612|
|United States, Louisiana|
|Tulane Medical Center|
|New Orleans, Louisiana, United States, 70112|
|United States, Maryland|
|University of Maryland|
|Baltimore, Maryland, United States, 21201|
|United States, New York|
|Children's Hospital at Montefiore Medical Center|
|Bronx, New York, United States, 10467|
|Mount Sinai Medical Center|
|New York, New York, United States, 10128|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|Study Chair:||Paul Goepfert, MD||University of Alabama at Birmingham|