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

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

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 Overview

• Status: Completed
• Conditions: HIV Infection

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.

• Study Type: Observational
• Enrollment (Actual): 113

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Ft. Lauderdale, Florida, United States, 33101
      • Children's Diagnostic and Treatment Center
    • Miami, Florida, United States, 33101
      • University of Miami-Jackson Memorial Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Cook County Children's Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • New York
    • Bronx, New York, United States, 10467
      • Children's Hospital at Montefiore Medical Center
    • New York, New York, United States, 10128
      • Mount Sinai Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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.	96 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	96 Weeks

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute on Drug Abuse (NIDA); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Mental Health (NIMH)
• Investigators: Study Chair: Paul Goepfert, MD, University of Alabama at Birmingham

Publications and helpful links

Helpful Links

• Website for the Adolescent Trials Network for HIV/AIDS Interventions

Study record dates

Study Major Dates

• Study Start: December 1, 2002
• Primary Completion (Actual): September 1, 2005
• Study Completion (Actual): September 1, 2005

Study Registration Dates

• First Submitted: April 4, 2005
• First Submitted That Met QC Criteria: April 4, 2005
• First Posted (Estimate): April 5, 2005

Study Record Updates

• Last Update Posted (Actual): February 28, 2017
• Last Update Submitted That Met QC Criteria: February 27, 2017
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: HIV infection; CD8+ T-cells; HIV-1 genotype
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; HIV Infections; Disease Progression
• Other Study ID Numbers: ATN 026