Immunologic Memory (Supp. of ATN 024)

Study Overview
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Brief Summary
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This is an exploratory, laboratory-based evaluation of cellular immune response to immunization with hepatitis B surface antigen in HIV-infected and HIV-uninfected adolescents. This is a substudy of ATN 024 and ATN 025. This substudy will compare cellular immune response in responders and nonresponders to immunization and also evaluate the relationship of these factors to the persistence of known correlates of serologic protection for the hepatitis B virus.

Detailed Description
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This substudy will enroll volunteers from participants of ATN 024 and ATN 025. Participants in ATN 024 are HIV-infected youths aged 12-24 years while participants in ATN 025 are HIV-uninfected youths aged 12-17 years. These youths must also be negative for HBV core antibody, HBV surface antigen, and HBV surface antibody to be eligible. Blood will be drawn from study participants prior to immunization, 1 month after completion of primary immunization and at study exit (week 72 for ATN 024 and week 76 for ATN 025) for cytokine assays and enumeration of antibody-secreting cells. In addition, the antibody to HBV surface antigen will be determined 2 and 4 weeks after supplemental immunization in nonresponders to the primary series and at study exit. This laboratory substudy is designed to evaluate some aspects of cellular immune response to hepatitis B vaccination that are directly related to the generation and durability of antibody response to HBV surface antigen in HIV-infected and HIV-uninfected adolescents. Cytokine production by peripheral mononuclear cells will be determined following in-vitro stimulation, and antibody-secreting cells will be enumerated.

Official Title
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Correlates of HBV-Specific B Cell Memory Following Vaccination in HIV-Infected Adolescents and HIV-Uninfected Adolescents: A Substudy of ATN 024 and ATN 025

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: Engerix B
* Biological: Twinrix for ATN 024
* Biological: Recombivax
* Biological: Twinrix for ATN 025


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects that are eligible for participation in ATN 024 and ATN 025 are eligible for ATN 048. Subjects consented for ATN 024 or ATN 025 should be consented for ATN 048 at the same time. A written informed assent/consent must be obtained from the subject along with written parental/legal guardian permission as determined by the local IRB before any study-related procedures are performed.

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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A1: ATN 024 Energix-B Standard Adult Dose<br> | Biological: Engerix B<br>* Standard adult dose for A1; increased adult dose for A2. Doses at Entry, Weeks 4 and 24. Non-responders (<10 IU/mL of antibody at week 28/4 weeks after dose #3) will receive Engerix-B increased adult dose at Week 48.<br>* Other names: There are no other names.;|
| Experimental: A2: ATN 024 Engerix-B Increased Adult Dose<br> | Biological: Engerix B<br>* Standard adult dose for A1; increased adult dose for A2. Doses at Entry, Weeks 4 and 24. Non-responders (<10 IU/mL of antibody at week 28/4 weeks after dose #3) will receive Engerix-B increased adult dose at Week 48.<br>* Other names: There are no other names.;|
| Active Comparator: A3: ATN 024 Twinrix Standard Adult Dose<br> | Biological: Twinrix for ATN 024<br>* Standard adult dosage, taken at Entry, Weeks 4 and 24. Non-responders (<10 IU/mL of antibody at week 28/4 weeks after dose #3) will receive Engerix-B increased adult dose at week 48.<br>* Other names: There are no other names.;|
| Experimental: B1: ATN 025 Recombivax<br> | Biological: Recombivax<br>* Dosage at entry and week 24; non-responders ((<10 IU/mL of antibody at week 28/4 weeks after dose #3) will receive 3rd dose of Recombivax during weeks 48-72.<br>* Other names: There are no other names.;|
| Experimental: B2: ATN 025 Twinrix<br> | Biological: Twinrix for ATN 025<br>* Doses at Entry and Week 24. Non-responders (<10 IU/mL of antibody at week 28/4 weeks after dose #3) will receive a dose of Recombivax during week 48-72.<br>* Other names: There are no other names.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure interferon-γ (IFN-γ), interleukin -4 (IL-4), and interleukin-10 (IL-10) production in serologic responders and non-responders. |  | Before and one month after receipt of primary series of immunization. | 
| To measure concentration of hepatitis B antibodies in serologic responders and non-responders. |  | 1, 2, and 4 weeks after supplemental vaccine dose. | 
| To measure concentration of antibody-secreting cells in serologic responders and non-responders. |  | Before and one month after receipt of primary series of immunization. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure whether the profile of cytokine secretion or the number of antibody-secreting cells can be used as a predictor of anamnestic response to a supplemental vaccine dose following serologic nonresponse to a primary series of immunization. |  | Prior to immunization, 1 month after primary immunization, at study exit (week 72 for ATN 024; week 76 for ATN 025); at 2 & 4 weeks after supplemental immunization in nonresponders, & at study exit for ATN 024 subjects. | 
| To compare the rate of loss of antibody-secreting cells after vaccination through the end of the study in each vaccine arm. |  | Prior to immunization, 1 month after completion of primary immunization and at study exit. | 

 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