Clinical trial NCT00107029: Evaluation of Genetic Markers as Explanations for the Observed Differences in Disease Progression in HIV+ Youth
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infection
Keywords: HIV infection
CD8+ T-cells
HIV-1 genotype
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: National Institute of Mental Health (NIMH)
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2005-04-05
Enrollment: 113
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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.

Brief summary: 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.

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 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

Primary outcomes:
measure: 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.
timeFrame: 96 Weeks
Secondary outcomes:
measure: 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.
timeFrame: 96 Weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Ft. Lauderdale
country: United States
facility: Children's Diagnostic and Treatment Center
state: Florida
city: Miami
country: United States
facility: University of Miami-Jackson Memorial Medical Center
state: Florida
city: Chicago
country: United States
facility: Cook County Children's Hospital
state: Illinois
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Bronx
country: United States
facility: Children's Hospital at Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: University of Alabama at Birmingham
name: Paul Goepfert, MD
role: STUDY_CHAIR
References: