Hepatitis B, HIV Infections
Conditions
Keywords
Hepatitis B Vaccine, Treatment Experienced, Treatment Naive
Brief summary
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
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.
Interventions
DRUGCpG7909 oligodeoxynucleotides (ODN)
BIOLOGICALHepatitis B virus vaccine
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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) | — |
| Percentage of patients who develop protective hepatitis B (HB) antibody concentration (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) | — |
| expression of costimulatory molecules on B-cells in peripheral blood (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) | — |
Countries
United States
Outcome results
None listed