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

Study Overview
=================
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.

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

Conditions
-----------------
HIV Infection

Participation Criteria
=================
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
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV infection, CD8+ T-cells, HIV-1 genotype