Safety and Effectiveness of an Adjuvant in Improving Immune Response to Hepatitis B Virus Vaccine in HIV Infected Individuals

National Institute of Allergy and Infectious Diseases (NIAID)48 enrolled

Overview

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a naturally occurring substance that is made by the body in response to infection or inflammation, and greatly improves cellular immune responses. The purpose of this study is to evaluate the safety and effectiveness of GM-CSF as an adjuvant to improve the immune response to hepatitis B virus (HBV) vaccination in HIV infected individuals.

Highly active antiretroviral therapy (HAART) has greatly improved the life of HIV infected individuals. Before the introduction of HAART, the impact of HBV infection and liver disease was less prominent due to the rapid progression to AIDS. However, with the use of HAART, liver disease has become a leading cause of death in HIV infected individuals; therefore, prevention of HBV infection is essential. Most HIV infected people respond poorly to HBV vaccines. GM-CSF is a cytokine produced primarily by activated T and B cells and has been used extensively as a hematopoietic growth factor. GM-CSF increases neutrophil count, improves antigen-presenting cell function, and is involved in the development and improvement of cellular immune responses. Past research has shown that GM-CSF improves the immune response to HBV vaccination in people with kidney disease. The purpose of this study is to evaluate the safety and effectiveness of GM-CSF as an adjuvant to improve the immune response to HBV vaccination in HIV infected individuals. This study will last 60 weeks. Participants will be randomly assigned to 1 of 2 arms. Arm A participants will receive 40 mcg of HBV vaccine at study entry, Week 4, and Week 12. Arm B participants will receive 40 mcg of HBV vaccine and 250 mcg of GM-CSF at study entry, Week 4, and Week 12. Participants will be stratified by their screening HIV-1 viral load. After completing the vaccination series, study visits will occur at Weeks 16, 36, and 60. Blood collection, a physical exam, and liver function and hepatitis antibody tests will be completed at all study visits. Telephone follow-up by study staff will occur 48 to 96 hours post-vaccination.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

Conditions

HIV Infections

Interventions

Hepatitis B virus vaccine with GM-CSF adjuvantBIOLOGICAL

Arm B participants will receive 40 mcg of HBV vaccine and 250 mcg of GM-CSF at study entry, Week 4, and Week 12.

Hepatitis B virus vaccineBIOLOGICAL

Arm A participants will receive 40 mcg of HBV vaccine at study entry, Week 4, and Week 12.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * HIV infected * CD4 count of 200 cells/mm3 or more within 30 days prior to study entry * HIV-1 RNA viral load value obtained within 30 days prior to study entry * Received HAART for at least 8 weeks prior to study entry OR not on HAART within 8 weeks prior to study entry with no plans to start HAART during the study. Participants receiving HAART must be on stable therapy as defined by the protocol. * Negative hepatitis B core total antibody (HBcAb total), qualitative hepatitis B surface antibody (HBsAb), and hepatitis B surface antigen (HBsAg) tests within 30 days prior to study entry * Negative hepatitis C virus (HCV) antibody test, completed within 30 days prior to study entry * Willing to use acceptable forms of contraception Exclusion Criteria: * HCV antibody or HCV RNA positive at any time prior to study entry * Previously vaccinated against HBV * Use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, vaccines, interleukins, interferons, growth factors, or intravenous immune globulin within 30 days prior to study entry * Known allergy or sensitivity to any component of the study drugs * Active drug or alcohol dependence that would interfere with participation in the study * Any mental illness that may interfere with the study * Serious illness requiring systemic treatment or hospitalization. Participants who complete therapy or are clinically stable on therapy for at least 14 days prior to study entry are not excluded. * Body weight less than 50 kg (110 lbs) * Abnormal lab values * Pregnant or breastfeeding

Locations (11)

Northwestern University CRS

Chicago, Illinois, United States

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Washington U CRS

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Quantitative hepatitis B surface antibody (HBsAb)

Time frame: At Week 16

Occurrence of Grade 3 or higher adverse events (including hypersensitivity reaction) related to study regimens and HIV viral load increase greater than 1 log(10)

Time frame: Throughout the study

Secondary Outcomes

Quantitative HBsAb 24 and 48 weeks after completion of HBV vaccination series

Time frame: At Weeks 36 and 60

HBsAb response, defined as titer greater than 10 mlU/ml at 4, 24, and 48 weeks after completion of HBV vaccination series

Time frame: At Weeks 16, 36, and 60

Changes in HIV viral load from baseline

Time frame: At Weeks 4, 16, and 60

Changes in white blood cell and absolute neutrophil count from baseline

Time frame: At Weeks 4, 16, and 36

Occurrence of Grade 2 or higher adverse events

Time frame: Throughout the study

Changes in CD4 count from baseline

Time frame: At Weeks 4, 16, and 60

Data from ClinicalTrials.gov

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