Hepatitis B Vaccination (HBV) in HIV Infected Children

Study Overview
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Brief Summary
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The purpose of this study is : To evaluate prevalence of protective hepatitis B antibody comparing intradermal (ID) and intramuscular (IM) route in antiHbsAb negative HIV infected children treated with highly active antiretroviral therapy (HAART) To revaccinate the HBV vaccine in the children who didn't have protective HBV Ab

Detailed Description
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Hepatitis B virus (HBV) and HIV share the same route of transmission and can have co-infection. The prevalence of this co-infection was 8.7% in Thai adult[1, 2] and 12.1% in African HIV vertically transmitted children[3]. Occurrence of HBV has effects to treatment due to having the same medication, lamivudine, tenofovir, emtricitabine or entecavir, to anti HIV medication. HBV can cause chronic liver disease, cirrhosis and hepatocellular carcinoma. In Thailand, the routine HBV vaccination program was started since 1992. Few reports in severe immune compromise HIV children has been shown to lose their expected preventive measles and hepatitis B antibody from history of scheduled vaccination even after the immune recovery by HAART[4, 5]. Limited data in of prevalence of protective hepatitis B antibody response after immune recovery in Thai HIV infected children treated with highly active antiretroviral therapy. In addition, HBV revaccination in this group of children should be considered[6]. The response of HBV revaccination intramuscularly (IM) at 0, 2 and 6 months in 63 HIV children shown response rates 17.4, 82.5, and 92.1% at 2, 6 and 7 months respectively[6]. Protective anti-HBs were shown in the majority of non-responders to IM HBV vaccine health care workers [21/23 (91.3%)] by two doses of intradermal route (ID)[7]. We hypothesize to see the faster and higher response of antiHBs after first dose of ID compare to IM in anti HBsAb negative HIV infected children. No randomized control trial compare antibody response between IM and ID route in HIV children after immune recovery. The benefit from this trial would be decreased the vaccine cost for resourced limited country.

Official Title
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Immunogenicity and Safety of Intradermal Compare to Intramuscular Hepatitis B Vaccination in HIV Children

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: Intradermal HBV 1 course
* Biological: Intramuscular HBV I course


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV infected individuals Age 1-18 years Current CD4 within 6 months ≥ 15% or ≥ 200 cells/ml in children age ≥ 6 years Signed written informed consent Negative HBs Ag, antiHBs, and antiHBc at screening visit Exclusion Criteria: Active AIDS Active opportunistic infection Platelet < 50,000/ mm3 at screening visit History of hypersensitivity to HBV vaccine Using oral steroid or immunosuppressive drugs

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>HBV ID | Biological: Intradermal HBV 1 course<br>* Dosage: 2 microgram (mcg), 0.1 ml per dose Location: left deltoid area x 1 injection Common reactions: local pain, low grade fever, small hyperpigmented induration (granulomatous reaction) which may last up to 6-12 months<br>|
| Active Comparator: 2<br>HBV IM | Biological: Intramuscular HBV I course<br>* Dosage: 2 microgram (mcg), 0.1 ml per dose Location: left deltoid area x 1 injection Common reactions: local pain, low grade fever, small hyperpigmented induration (granulomatous reaction) which may last up to 6-12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of children with protective antiHBs at 8 weeks after first dose of HBV ID is superior to HBV IM |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of children with positive antiHBs at 4 weeks after second and third dose of HBV |  | 4 weeks | 
| Number of adverse events in HBV ID group and HBV IM group |  | 7 months | 
| Proportion of protective antiHBs in HIV children after protocol defining immune recovery |  | 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBV vaccine, HIV children, immune recovery, HBV antibody, Intradermal, Intramuscular, antibody response after HBV vaccine, treatment experienced