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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT00107029

Enrollment

113

Registered

2005-04-05

Start date

2002-12-31

Completion date

2005-09-30

Last updated

2017-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV Infection

Keywords

HIV infection, CD8+ T-cells, HIV-1 genotype

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

OTHER

Eligibility

Sex/Gender

ALL

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Demonstrate that few CTL escape mutations occur in HIV-1 specific CD8+ T cell epitopes that are HLA-B27 and B57 restricted, when compared to those restricted by HLA-B35 and B53.	96 Weeks	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

Measure	Time frame	Description
Demonstrate that CD8+ T cells have a high functional avidity to HLA-B27 and B57 bound epitopes when compared to those responding to HLA-B35 and B53 bound epitopes.	96 Weeks	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.

Countries

United States

Outcome results