Determining Responses to Two Different Vaccines in HIV and HCV Infected Individuals

This study has been completed.
Sponsor:
Collaborator:
AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00393276
First received: October 25, 2006
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

Infection with either HIV or hepatitis C virus (HCV) affects immune system responses. The purpose of this study is to investigate the immune responses to two different vaccine formulations in HIV-infected, HCV-infected, and HCV/HIV- coinfected individuals.


Condition Intervention Phase
HIV Infections
Hepatitis C
Biological: Twinrix
Biological: Decavac
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Optimizing Vaccine Responsiveness in HIV-1 and HCV Infections by Identifying Determinants of Responsiveness: A Pilot Study

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • B-cell humoral responses [ Time Frame: At Week 8 ] [ Designated as safety issue: Yes ]
  • T-cell responses as reflected by hepatitis B and tetanus antibody titers [ Time Frame: At Week 8 ] [ Designated as safety issue: Yes ]
  • Dendritic cell, B-cell, and T-cell functional markers [ Time Frame: At Study Entry ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • B-cell functional marker [ Time Frame: At Week 6 ] [ Designated as safety issue: Yes ]
  • T-cell responses to hepatitis A, hepatitis B, and tetanus antigens [ Time Frame: At Weeks 3 and 8 ] [ Designated as safety issue: Yes ]
  • Longitudinal serum antibody titers to hepatitis A, hepatitis B, and tetanus (B-cell responses) [ Time Frame: At Study Entry and Weeks 1, 3, 6, 8, 12, and 24 ] [ Designated as safety issue: Yes ]
  • CD4/CD8 and HCV genotype [ Time Frame: At Study entry ] [ Designated as safety issue: No ]
  • Baseline antibody status for hepatitis B core antigen (anti-HBc) [ Time Frame: At Study entry ] [ Designated as safety issue: No ]

Enrollment: 29
Study Start Date: August 2007
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
HCV-infected defined as a positive result using polymerase chain reaction (PCR) without previous HCV-based therapy and without the presence of Child's B or C cirrhosis. These participants will be HIV-uninfected.
Biological: Twinrix
Combined hepatitis A and hepatitis B immunization
Biological: Decavac
Diphtheria and tetanus toxoid vaccine
Experimental: B
HIV-infected and ARV naive, with a CD4 cell count of 300 cells/mm3 or greater, with no prior or current opportunistic infection, and with no indication for HIV therapy. These participants will be HCV-uninfected.
Biological: Twinrix
Combined hepatitis A and hepatitis B immunization
Biological: Decavac
Diphtheria and tetanus toxoid vaccine
Experimental: C
HCV/HIV-coinfected as defined above in Arms A and B.
Biological: Twinrix
Combined hepatitis A and hepatitis B immunization
Biological: Decavac
Diphtheria and tetanus toxoid vaccine

Detailed Description:

Individuals with HCV and HIV coinfection are especially hard to treat, and as a result, account for a high rate of deaths each year. Because HCV and HIV share transmission routes, HCV/HIV coinfection is common. Liver disease has emerged as a significant cause of death in individuals coinfected with HCV and HIV. Currently, the mechanisms by which HCV and HIV interact in HCV/HIV-coinfected individuals, including how these infections affect immune responses, are poorly understood. Research suggests that vaccination may prevent other comorbidities associated with HCV/HIV coinfection; however, responses to new vaccine antigens have been shown to be impaired in HCV or HIV-infected individuals. The purpose of this study is to identify the innate and adaptive immune defects present in HCV-infected, HIV-infected, and HCV/HIV-coinfected individuals. This study will evaluate whether these innate and adaptive immune defects predict responses to HBV neoantigen in the form of both a diphtheria/tetanus toxoid immunization (Decavac)and a hepatitis A-hepatitis B immunization (Twinrix).

This study will last approximately 24 weeks. Participants will be stratified to one of three arms, based on their HCV and HIV status:

  • Arm A will enroll HCV-infected individuals who are HIV-uninfected
  • Arm B will enroll HIV-infected individuals who are HCV-uninfected
  • Arm C will enroll HCV/HIV-coinfected individuals

Arms B and C will open for enrollment before Arm A. Opening of enrollment for Arm A will be determined by the accrual progress of Arms B and C as evaluated by the ACTG Scientific Agenda Steering committee.

All participants will receive Decavac vaccination on Day 0, and a Twinrix vaccination on Days 0, 7, and 21. Study visits will occur around Days 0, 7, and 21, and at Weeks 6, 8, 12, and 24; all visits will include medical and medication history, blood collection, and a physical exam. Medication to treat HCV or HIV will not be provided by the study.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Arm A Participants:

  • HCV-infected
  • HIV-uninfected

Inclusion Criteria for Arm B Participants:

  • HIV-infected
  • HCV-uninfected
  • CD4 count greater than or equal to 300 cells/mm3 within 60 days prior to study entry

Inclusion Criteria for Arm C Participants:

  • HIV-infected
  • HCV-infected

Inclusion Criteria for All Participants:

  • Documented hepatitis B virus (HBV) antibody status. If anti-HBV core antibody positive, documented HBV negative test within 30 days prior to study entry is required.
  • Willing to use acceptable forms of contraception for the duration of the study and for 24 weeks after the last vaccination

Exclusion Criteria for Arm A Participants:

  • Concurrent or recent treatment for HCV infection (within the past three months)

Exclusion Criteria for Arm B Participants:

  • Current, prior, or clinical need for antiretroviral therapy (within the past three months prior to study entry)
  • Opportunistic infection other than HCV

Exclusion Criteria for Arm C Participants:

  • Concurrent or recent treatment for HCV infection (within the past three months)
  • Current, prior, or clinical need for antiretroviral therapy (within the past three months prior to study entry). More information on this criterion can be found in the protocol.
  • Opportunistic infection other than HCV

Exclusion Criteria for All Participants:

  • History of exposure to hepatitis A vaccine, hepatitis B vaccine, or combined hepatitis A-hepatitis B vaccines
  • Immunomodulatory agents for 7 days or more within 30 days prior to study entry. More information on this criterion can be found in the protocol.
  • Concurrent immunizations (e.g., influenza, pneumococcal, other vaccine)within 3 days prior to study entry
  • Active or recent (in the last six months prior to study entry) CDC Category C event. More information on this criterion can be found in the protocol
  • Systemic anticancer chemotherapy or radiation within 24 weeks prior to study entry, or anticipated need to begin such treatment
  • Past or current immunologically-mediated disease. More information on this criterion can be found in the protocol.
  • Current bacterial infection requiring treatment, therapy, or hospitalization within 1 week prior to study entry
  • Serious illness requiring systemic treatment and/or hospitalization. Participants who complete therapy or are clinically stable on therapy for at least 14 days prior to study entry are not excluded.
  • Current uncontrolled seizure disorders
  • Active bleeding varices, or Child's B or C cirrhosis. More information on this criterion can be found in the protocol.
  • Serious bleeding disorder that poses a risk to a participant for intramuscular injections
  • Known allergy or sensitivity to study vaccines or their formulations
  • Current drug or alcohol use that, in the opinion of the investigator, interferes with study participation
  • Pregnant or breastfeeding
  • Use of systemic investigational agents within 30 days prior to entry
  • History of any hepatitis A vaccine within one year
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00393276

Locations
United States, California
Ucsd, Avrc Crs
San Diego, California, United States, 90502
Ucsf Aids Crs
San Francisco, California, United States, 94110
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80045
United States, Maryland
IHV Baltimore Treatment CRS
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital Clinical Research Site (MGH CRS) CRS
Boston, Massachusetts, United States, 02114
United States, New York
HIV Prevention & Treatment CRS
New York, New York, United States
United States, North Carolina
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
United States, Ohio
Case CRS
Cleveland, Ohio, United States, 44106-5083
MetroHealth CRS
Cleveland, Ohio, United States, 44109
The Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Texas
Trinity Health and Wellness Center CRS
Dallas, Texas, United States
Puerto Rico
Puerto Rico AIDS Clinical Trials Unit CRS
San Juan, Puerto Rico
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: Donald D. Anthony, MD, PhD Case Western Reserve University
Study Chair: Benigno Rodriguez, MD Division of Infectious Diseases, University Hospital of Cleveland
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00393276     History of Changes
Other Study ID Numbers: A5232, 10154, 1R21AI066957-01, ACTG A5232
Study First Received: October 25, 2006
Last Updated: January 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Experienced
Treatment Naive
Immunizations

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Hepatitis C
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Hepatitis, Viral, Human
Flaviviridae Infections
Hepatitis
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on October 19, 2014