Evaluation of Genetic Markers as Explanations for the Observed Differences in Disease Progression in HIV+ Youth

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00107029
First received: April 4, 2005
Last updated: October 8, 2013
Last verified: August 2013
  Purpose

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.


Condition
HIV Infection

Study Type: Observational
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

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 113
Study Start Date: December 2002
Study Completion Date: September 2005
Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Subjects who were identified as HLA Class I HLA-B*27, B*35, B*53, and/or B*57 positive from the REACH study will be contacted for their interest in participating in this study. Only former REACH sites in the ATN will be eligible to enroll subjects into this study.

Criteria

Inclusion Criteria:

  • HLA-Class I HLA-B*27, B*35, B*53 and/or B*57 positive identified through the REACH study
  • Subject's ability and willingness to provide written informed consent
  • Subject's ability and willingness to be followed at least one year on this ATN 026 study

Exclusion Criteria:

  • On chronic immunosuppressive therapy, not including topical or inhaled steroid use.
  • Any prohibited medication listed in protocol within 2 weeks prior to the Entry visit labs
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00107029

Locations
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
Sponsors and Collaborators
Investigators
Study Chair: Paul Goepfert, MD University of Alabama at Birmingham
  More Information

Additional Information:
No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00107029     History of Changes
Other Study ID Numbers: ATN 026
Study First Received: April 4, 2005
Last Updated: October 8, 2013
Health Authority: United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
HIV infection
CD8+ T-cells
HIV-1 genotype

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Disease Progression
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on April 14, 2014