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

October 25, 2006
January 15, 2014
August 2007
July 2009   (final data collection date for primary outcome measure)
  • 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 ]
  • T-cell responses as reflected by hepatitis A, hepatitis B, and tetanus antibody titers at Weeks 0, 3, and 8
  • B-cell responses as reflected by hepatitis A, hepatitis B, and tetanus antibody titers at Week 8
  • Human dendritic cell (DC), B-cell and T-cell frequency/functional markers at baseline
Complete list of historical versions of study NCT00393276 on ClinicalTrials.gov Archive Site
  • 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 ]
  • DC, B-cell, and T-cell functional markers during 24 weeks of study follow-up
  • CD4/CD8 counts at study entry and HCV genotype at study entry
  • B-cell and T-cell response throughout 24 weeks of study follow-up
  • baseline dichotomous test for antibodies to hepatitis B core antigen (anti-HBc) and hepatitis B virus (HBV) DNA
Not Provided
Not Provided
 
Determining Responses to Two Different Vaccines in HIV and HCV Infected Individuals
Optimizing Vaccine Responsiveness in HIV-1 and HCV Infections by Identifying Determinants of Responsiveness: A Pilot Study

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
  • HIV Infections
  • Hepatitis C
  • Biological: Twinrix
    Combined hepatitis A and hepatitis B immunization
  • Biological: Decavac
    Diphtheria and tetanus toxoid vaccine
  • 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.
    Interventions:
    • Biological: Twinrix
    • Biological: Decavac
  • 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.
    Interventions:
    • Biological: Twinrix
    • Biological: Decavac
  • Experimental: C
    HCV/HIV-coinfected as defined above in Arms A and B.
    Interventions:
    • Biological: Twinrix
    • Biological: Decavac

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
29
July 2009
July 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT00393276
A5232, 10154, 1R21AI066957-01, ACTG A5232
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
AIDS Clinical Trials Group
Study Chair: Donald D. Anthony, MD, PhD Case Western Reserve University
Study Chair: Benigno Rodriguez, MD Division of Infectious Diseases, University Hospital of Cleveland
National Institute of Allergy and Infectious Diseases (NIAID)
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP