Hepatitis B Vaccine Genetics: A Substudy of ATN 024 and ATN 025

Study Overview
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Brief Summary
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This laboratory-based substudy of an effectiveness trial of two Hepatitis B vaccines in HIV-negative youths is being done to evaluate the genetic contribution to the individualized immune response.

Detailed Description
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This laboratory-based substudy of ATN 024 and 025 will evaluate the genetic contribution to highly individualized immune responses to hepatitis B vaccine in individuals and confirm the correlation of specific human leukocyte antigen (HLA) alleles and haplotypes with Hepatitis B Virus (HVB) antibody concentrations and antibody decay kinetics in vaccinated adolescents. Approximately 5 ml of whole blood will be collected from study participants at the time of the week 28 visit or at any subsequent study visit or clinic visit following successful completion of the week 28 visit. Peripheral blood mononuclear cells will be obtained and QIA amp Blood kit will be used to extract high-quality genomic DNA for polymerase chain reaction-based genotyping by the PEII laboratory. The study is expected to be available for the duration of the parent studies which is approximately 2 years. This study requires one visit that may be arranged to coincide with a study or routine clinic visit. There are no follow up visits.

Official Title
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Population Genetics and Immune Response to Hepatitis B Vaccination in Adolescents: A Substudy of ATN 024 and ATN 025

Conditions
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HIV Infection, Hepatitis B

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects currently enrolled in ATN 024 or ATN 025 are eligible for enrollment in ATN 052 beginning at or following completion of the week 28 visit. Subjects previously enrolled in ATN 024 or ATN 025 are eligible for enrollment in ATN 052, unless the subject was prematurely discontinued from the study prior to the first post-vaccination serology assessment which is performed at week 28. Current pregnancy is permitted. A signed informed assent/consent must be obtained from the subject. Written parental or guardian permission must be obtained where required by the institutional review board/ethics committee (IRB/EC). Exclusion Criteria: Inadequate post-vaccination serology evaluation in ATN 024 or ATN 025. Unable to obtain informed consent and/or parental/legal guardian permission where required by the local IRB/EC.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1 - HIV Positive<br>Participant in parent study ATN 024, aged 12-24 years, testing HIV positive. All eligible youths must be negative for HBV core antibody, HBV surface antigen, and HBV surface antibody at the time of enrollment in to ATN 024. | |
| 2 - HIV Negative<br>Participant in parent study ATN 025, aged 12-24 years and testing negative for HIV infection. All eligible youths must be negative for HBV core antibody, HBV surface antigen, and HBV surface antibody at the time of enrollment in to ATN 025. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To confirm the correlation of HLA-DRB1 and HLA-DQB1 alleles and haplotypes with HBV antibody concentrations and antibody decay kinetics in vaccinated adolescents. |  | Specimen obtained at or after the first post- vaccination serology visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine if other genetic variations (768 single nucleotide polymorphisms (SNP) in about 50 genes) in the immune response pathways can confer additional effects on immune responses to hepatitis B vaccination. |  | Specimen obtained at or after the first post-vaccination serology visit. | 
| To compare the strength of genetic and non-genetic associations with specific antibody responses following HBV vaccination. |  | Specimen obtained at or after the first post-vaccination serology visit. | 
| To explore similarities and differences in genetic associations between HIV-positive and HIV-negative cohorts. |  | Specimen obtained at or after the first post-vaccination serology visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B vaccines, HIV-infected adolescents, Hepatitis B infection (negative), HIV vaccine trial