HBV Vaccination in HIV-infected Adults

Study Overview
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Brief Summary
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The finding of isolated hepatitis B core antibody (isolated HBc) in absent of recent active hepatitis could cause by several scenarios, including false positive, remote infection without viremia, and occult infection with low viremia. Hepatitis B virus (HBV) vaccine booster could be a great prevention strategy for those who do not have HBV viremia. There is no standard consensus for management of this issue especially among HIV infected population. In addition, prior studies revealed that HIV-infected individuals had lower immunologic response to HBV vaccine than general population. This study intends to compare the immune response and safety of 4- versus 3-standard dose of hepatitis B virus vaccination in HIV-infected adults who has isolated HBc. The immunologic response will be evaluated after the participants receive vaccination.

Detailed Description
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A randomized controlled trial to evaluate differences in immunogenicity and safety of the two hepatitis B vaccination regimens, including the percentage of responders, high-level responders, anamnestic response, geometric mean titers of anti-HBs antibody, adverse events and predictive factors associated with vaccine responsiveness After participant enrollment, data on baseline characteristics, time since HIV diagnosis, CD4 counts, HIV viral load, antiretroviral treatment regimen and duration will be collected, then the participants will be randomized into 2 groups to receive either 3- or 4-standard doses (20 mcg per dose) of HBV vaccination, and follow-up blood test for anti-HBs titers at multiple pre-specified time points to evaluate outcomes

Official Title
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Immunogenicity and Safety of 4- vs. 3-standard Doses HBV Vaccination in HIV-infected Adults With Isolated Anti-HBc Antibody

Conditions
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Hepatitis B Vaccination, HIV

Intervention / Treatment
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* Biological: Hepatitis B vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years On combination antiretroviral therapy (cART) CD4 ≥ 200 cell/mm3 for ≥ 1 year HIV viral load < 20 copies/ml for ≥ 1 year Isolated anti-HBc Ab (negative HBsAg, anti-HBs Ab) and negative anti-HCV at screening Exclusion Criteria: Pregnancy Previous HBV vaccination Intolerance to any component of HBV vaccine Transaminitis in the past 3 months (≥ 5 UNL) Ongoing opportunistic infection (OI) Active malignancy, with current chemotherapy or radiotherapy Systemic steroid therapy (≥ 0.5 mg/kg/day) or any immunomodulating therapy in the last 6 months Other immunocompromised disorders (e.g. solid organ transplant) Asplenism Renal insufficiency (CrCl ≤ 30 mL/min) Decompensated cirrhosis (Child-Pugh C)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Interventional Model Description: Open-label, randomized controlled trial (RCT) with 1:1 allocation in parallel arms
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 3-standard dose HBV vaccination group<br>participants will receive 3 standard doses of HBV vaccination at 0, 1, 6 months | Biological: Hepatitis B vaccine<br>* Hepatitis B vaccine (20 mcg/ml) 1 ml intramuscular injection in 3 (at 0, 1, 6 months) or 4 doses (0, 1, 2, 6 months)<br>|
| Active Comparator: 4-standard dose HBV vaccination group<br>participants will receive 4 standard doses of HBV vaccination at 0, 1, 2, 6 months | Biological: Hepatitis B vaccine<br>* Hepatitis B vaccine (20 mcg/ml) 1 ml intramuscular injection in 3 (at 0, 1, 6 months) or 4 doses (0, 1, 2, 6 months)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunologic response to 4 versus 3 doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody, demonstrated by percentage of responders (with anti-HBs Ab ≥ 10 mIU/mL ) at week 28 | Immunologic response to 4 versus 3 doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody, demonstrated by percentage of responders (with anti-HBs Ab ≥ 10 mIU/mL ) at week 28 | 28 weeks after the first dose of HBV vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anamnestic response at week 4 | Anamnestic response at week 4 | 4 weeks after the first dose of HBV vaccination | 
| Percentage of responders (with anti-HBs Ab ≥ 10 mIU/mL) at month 12 | Percentage of responders (with anti-HBs Ab ≥ 10 mIU/mL) at month 12 | 12 months after the first dose of HBV vaccination | 
| Percentage of high-level responders (with anti-HBs Ab ≥ 100 mIU/mL) at week 28 and month 12 | Percentage of high-level responders (with anti-HBs Ab ≥ 100 mIU/mL) at week 28 and month 12 | 28 weeks and 12 months after the first dose of HBV vaccination | 
| Intensity and frequency of vaccine adverse event (AE) | Intensity and frequency of vaccine adverse event (AE) | 1 year | 
| Geometric mean titers of anti-HBs Ab at week 28 and month 12 | Geometric mean titers of anti-HBs Ab at week 28 and month 12 | 28 weeks and 12 months after the first dose of HBV vaccination | 
| Predictive factors associated with response to vaccine (age, sex, CD4 count) | Predictive factors associated with response to vaccine (age, sex, CD4 count) | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBV vaccination, HIV, isolated anti-HBc