Safety of and Immune Response to a Hepatitis B Virus Vaccine Given With a Booster (CpG7909 ODN) in HIV Infected and HIV Uninfected People

Study Overview
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Brief Summary
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The purpose of the study is to determine the safety of and immune response to a hepatitis B virus vaccine series given with a boosting agent, CpG7909 oligodeoxynucleotides (ODN), in HIV infected and HIV uninfected individuals who previously failed to develop a response to hepatitis B vaccine. Study hypothesis: Administration of CpG7909 ODN together with recombinant hepatitis B vaccine will result in increased frequency and magnitude of response to vaccine in individuals who have previously failed to mount a response to vaccination, and that in HIV infected subjects with detectable plasma viremia, it will lead to the enhancement of HIV-specific responses.

Detailed Description
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As HIV disease progresses in HIV infected people, their immune responses to infectious and other foreign invaders becomes weaker; in particular, the cellular (T-cell) immune response is particularly affected by HIV. A boosting agent called CpG7909 ODN may be an ideal adjuvant for vaccines given to HIV infected people, because it may help elicit an increased CD8 T-cell response. This study will evaluate the safety of and immune response to a hepatitis B virus vaccine series given with CpG7909 ODN in HIV infected and uninfected people. There will be three groups in this study; participants will be stratified by baseline CD4 counts and viral load. Within each group, participants will be randomly assigned to receive 3 injections of hepatitis B vaccine with CpG7909 ODN or 3 injections of hepatitis B vaccine alone. Injections will be given at study entry and Months 1 and 6. There will be 10 study visits; a physical exam and blood collection will occur at each visit.

Official Title
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Immunologic Effects of CpG ODN Administration to HIV Uninfected and HIV Infected Patients

Conditions
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HIV Infections, Hepatitis B

Intervention / Treatment
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* Drug: CpG7909 oligodeoxynucleotides (ODN)
* Biological: Hepatitis B virus vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for HIV Infected Participants: HIV-1 infection If receiving combination antiretroviral therapy (ART), must have been on ART for at least 3 months prior to study entry. Patients who anticipate a change in treatment (either initiating ART or stopping ART) in the next 7 months are not eligible. CD4 count of 250 cells/mm3 or greater Negative HBsAb, HBsAg, and HBcAb Willing to use acceptable forms of contraception while on study treatment and for 24 weeks after study treatment has ended Inclusion Criteria for HIV Uninfected Participants: HIV uninfected Negative HBsAb, HBsAg, and HBcAb Willing to use acceptable forms of contraception while on study treatment and for 24 weeks after study treatment has ended Exclusion Criteria for All Participants: Cancer. Participants with squamous cell or basal cell skin cancer are not excluded. Autoimmune disease Immunosuppressive medications. People who use or have used corticosteroid nasal sprays are not excluded. People who have received fewer than 2 weeks of systemic corticosteroids with the last dose over a month prior to study entry are not excluded. Any medical or psychiatric condition or occupational responsibilities that may interfere with the study Immunomodulator or investigational agent therapy within 30 days prior to study entry Allergy/sensitivity to study drugs or their formulations, including thimerosal Current drug or alcohol use that, in the opinion of the investigator, would interfere with the study Active hepatitis C virus infection, as indicated by serum antibodies to HCV AND detectable HCV RNA in plasma Blood clotting abnormalities Any other condition that, in the opinion of the investigator, might interfere with the study Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: CpG7909 oligodeoxynucleotides (ODN)|nan|
|Biological: Hepatitis B virus vaccine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of HIV peptides to which HIV infected patients respond using ELISPOT (CpG vs. no CpG in HIV infected participants) |  |  | 
| total number of CD8+ lymphocytes responding after HIV-peptide stimulation using ELISPOT (CpG vs. no CpG in HIV infected participants) |  |  | 
| safety |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who develop protective hepatitis B (HB) antibody concentration (CpG vs. no CpG in HIV infected participants) |  |  | 
| percentage of patients who develop HB specific CD8+ lymphocyte responses using ELISPOT (CpG vs. no CpG in HIV infected participants) |  |  | 
| percentage of patients who develop HB specific CD8+ lymphocyte responses using ELISPOT (CpG vs. no CpG in all participants) |  |  | 
| percentage of patients who develop CD8+ lymphocyte proliferative responses as measured using CFSE (CpG vs. no CpG in HIV infected participants) |  |  | 
| percentage of patients who develop CD8+ lymphocyte proliferative responses as measured using CFSE (CpG vs. no CpG in all participants) |  |  | 
| expression of costimulatory molecules on B-cells in peripheral blood (CpG vs. no CpG in HIV infected participants) |  |  | 
| expression of costimulatory molecules on B-cells in peripheral blood (CpG recipients, HIV infected vs. uninfected participants) |  |  | 
| spontaneous IFN-gamma production in peripheral blood (CpG recipients, HIV infected vs. uninfected participants) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B Vaccine, Treatment Experienced, Treatment Naive