Modified Dose and Schedule of Recombinant Hepatitis B Vaccination in HIV-infected Adult Subjects

Study Overview
=================
Brief Summary
-----------------
The purposes of this study include 1) to compare the seroconversion rate of an intensive standard-dose regimen (0, 1, 2 and 6 months) to a standard-dose regimen (0,1 and 6 months), and 2) to compare the seroconversion rate of an intensive double-dose regimen (40 μg at 0,1,2 and 6 months) to a standard-dose regimen (20 μg at 0,1 and 6 months) of HBV vaccine in HIV-infected adult patients.

Detailed Description
-----------------
HIV and HBV share similar risk factors and routes of transmission. HIV/HBV coinfection is associated with greater chance of chronic HBV carrier state, higher level of HBV replication and increasing its potential for transmission. Currently, there are no concrete data to determine the best HBV vaccination schedule in HIV-infected patients. Standard HBV vaccination (20 μg at 0, 1 and 6 months) gives seroconversion rate of 33-63% in HIV-infected individuals compared with >90% in healthy individuals. This study aims to compare the efficacy of an intensive standard-dose regimen (0, 1, 2 and 6 months) to a standard-dose regimen (0,1 and 6 months) and to compare the seroconversion rate of an intensive double-dose regimen (40 μg at 0,1,2 and 6 months) to a standard-dose regimen (20 μg at 0,1 and 6 months) of HBV vaccine in HIV-infected adult patients with CD4 level above 200 permm3 and suppressed viral load.

Official Title
-----------------
Open-Label, Randomized Controlled Trial Comparing Three Strategies of Hepatitis B Vaccination in HIV-1-Infected Patients With CD4 Cell Counts Above 200 permm3 and Suppressed Viral Load

Conditions
-----------------
HIV Infection

Intervention / Treatment
-----------------
* Biological: Hepavax-Gene
* Biological: Hepavax-Gene
* Biological: Hepavax-Gene


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Positive for anti-HIV antibody At least 18 years of age CD4 > 200 cell/mm3 On antiretroviral therapy Viral load < 50 copies/ml Negative for any HBV serological marker (HBsAg, Anti-HBs, Anti-HBc) No history of previous hepatitis B vaccination Anti-HCV negative No active opportunistic infection at the time of screening Willing to sign informed consent Able to follow up Exclusion Criteria: Pregnancy or breast feeding History of hypersensitivity to any component of vaccine Diagnosis of malignancy and receiving chemotherapy or radiation Other immunocompromised conditions not related to HIV infection (solid-organ transplantation, chemotherapy in the last 6 months) On Immunosuppressive treatment, immunomodulating treatment or corticosteroid (equal or above 0.5 mg per kg per day of prednisolone) Renal failure (creatinine clearance < 30 mL/min) Decompensated cirrhosis (child-pugh C) Not able to follow up

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: Arm A<br>20 μg of Hepavax-gene intramuscularly injections at deltoid region at 0,1 and 6 months | Biological: Hepavax-Gene<br>* 20 μg of Hepavax-gene intramuscularly injections at deltoid region at 0,1 and 6 months<br>* Other names: Berna;|
| Experimental: Arm B<br>20 μg of Hepavax-gene intramuscularly injections at deltoid region at 0,1,2 and 6 months | Biological: Hepavax-Gene<br>* 20 μg of Hepavax-gene intramuscularly injections at deltoid region at 0,1,2 and 6 months<br>* Other names: Berna;|
| Experimental: Arm C<br>40 μg of Hepavax-gene intramuscularly injections at deltoid region at 0,1,2 and 6 months | Biological: Hepavax-Gene<br>* 40 μg of Hepavax-gene intramuscularly injections at deltoid region at 0,1,2 and 6 months<br>* Other names: Berna;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate (percentage of subjects with anti-HBs antibody titer >= 10 IU/L) at day 210 | To compare the seroconversion rate at day 210 of an intensive standard-dose regimen (0, 1, 2 and 6 months) to a standard-dose regimen (0,1 and 6 months) To compare the seroconversion rate at day 210 of an intensive double-dose regimen (40 μg at 0,1,2 and 6 months) to a standard-dose regimen (20 μg at 0,1 and 6 months) of HBV vaccine in HIV-infected adult patients | Day 210 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotective rate (percentage of subjects with anti-HBs antibody titer >= 10 IU/L) at 1 year | To determine the seroprotective rate at 1 year of each of the vaccination regimens. | 1 year | 
| Number of subjects with adverse events after vaccination | Adverse events include pain at injected site, swelling at injected site, redness at injected site, fever, headache, fatique and anaphylaxis | 180 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis B vaccine, HIV infection, Modified HBV vaccine dose, Modified HBV vaccine schedule