HBV Vaccination in HIV-infected Adults

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

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.

Study Overview

• Status: Unknown
• Conditions: Hepatitis B Vaccination, HIV
• Intervention / Treatment: Biological: Hepatitis B vaccine

Detailed Description

• 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

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Chiang Mai
    • Muang, Chiang Mai, Chiang Mai, Thailand, 50200
      • Recruiting
      • Maharaj Nakorn Chiang Mai Hospital, Department of Medicine, Chiang Mai University
      • Contact: Romanee Chaiwarith, MD; Phone Number: +66-5393-6457; Email: rchaiwar@gmail.com
      • Contact: Quanhathai Kaewpoowat, MD; Phone Number: +66-5393-6457; Email: quanhathai@rihes.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 3-standard dose HBV vaccination group; participants will receive 3 standard doses of HBV vaccination at 0, 1, 6 months	Biological: Hepatitis B vaccine; 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)
ACTIVE_COMPARATOR: 4-standard dose HBV vaccination group; participants will receive 4 standard doses of HBV vaccination at 0, 1, 2, 6 months	Biological: Hepatitis B vaccine; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chiang Mai University

Publications and helpful links

General Publications

• Laksananun N, Praparattanapan J, Kotarathititum W, Supparatpinyo K, Chaiwarith R. Immunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody. AIDS Res Ther. 2019 May 3;16(1):10. doi: 10.1186/s12981-019-0225-3.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2017
• Primary Completion (ANTICIPATED): February 1, 2018
• Study Completion (ANTICIPATED): July 1, 2018

Study Registration Dates

• First Submitted: July 6, 2017
• First Submitted That Met QC Criteria: July 6, 2017
• First Posted (ACTUAL): July 11, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 11, 2017
• Last Update Submitted That Met QC Criteria: July 6, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: HBV vaccination, HIV, isolated anti-HBc
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; Hepatitis B
• Other Study ID Numbers: 04565

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No