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

October 28, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico
        • Puerto Rico AIDS Clinical Trials Unit CRS
  • United States
    • California
      • San Diego, California, United States, 92103
        • UCSD Antiviral Research Center CRS
      • San Francisco, California, United States, 94110
        • Ucsf Aids Crs
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital CRS
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • IHV Baltimore Treatment CRS
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Clinical Research Site (MGH CRS) CRS
    • New York
      • New York, New York, United States, 10032-3732
        • Columbia P&S CRS
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Univ. Med. Ctr. Adult CRS
    • Ohio
      • Cleveland, Ohio, United States, 44106-5083
        • Case CRS
      • Cleveland, Ohio, United States, 44109
        • MetroHealth CRS
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Medical Center
    • Texas
      • Dallas, Texas, United States
        • Trinity Health and Wellness Center CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
B-cell humoral responses
Time Frame: At Week 8
At Week 8
T-cell responses as reflected by hepatitis B and tetanus antibody titers
Time Frame: At Week 8
At Week 8
Dendritic cell, B-cell, and T-cell functional markers
Time Frame: At Study Entry
At Study Entry

Secondary Outcome Measures

Outcome Measure
Time Frame
B-cell functional marker
Time Frame: At Week 6
At Week 6
T-cell responses to hepatitis A, hepatitis B, and tetanus antigens
Time Frame: At Weeks 3 and 8
At Weeks 3 and 8
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
At Study Entry and Weeks 1, 3, 6, 8, 12, and 24
CD4/CD8 and HCV genotype
Time Frame: At Study entry
At Study entry
Baseline antibody status for hepatitis B core antigen (anti-HBc)
Time Frame: At Study entry
At Study entry

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

July 1, 2009

Study Completion (Actual)

July 1, 2009

Study Registration Dates

First Submitted

October 25, 2006

First Submitted That Met QC Criteria

October 25, 2006

First Posted (Estimate)

October 27, 2006

Study Record Updates

Last Update Posted (Actual)

November 1, 2021

Last Update Submitted That Met QC Criteria

October 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A5232
  • 10154 (Registry Identifier: DAIDS ES Registry Number)
  • 1R21AI066957-01 (U.S. NIH Grant/Contract)
  • ACTG A5232

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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