Determining Responses to Two Different Vaccines in HIV and HCV Infected Individuals - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	AIDS Clinical Trials Group
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00393276

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 I

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:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Hepatitis Hepatitis A Hepatitis B Hepatitis C Tetanus

Drug Information available for: Twinrix Diphtheria-Tetanus Vaccine

U.S. FDA Resources

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 ]

Estimated Enrollment:	66
Study Start Date:	March 2007
Study Completion Date:	September 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

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

Locations

United States, California
Ucsd, Avrc
San Diego, California, United States, 90502
UCSF PHP, San Francisco Gen. Hospital
San Francisco, California, United States, 94110
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80045
United States, Maryland
Johns Hopkins School of Medicine, ACTU
Baltimore, Maryland, United States, 21287-8106
Univ. of Maryland Biotechnology Institute, Institue of Human Virology
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital, Division of Infectious Diseases
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63108
United States, New York
Columbia University HIV Prevention and Treatment Research Group
New York, New York, United States, 10032-3784
University of Rochester Medical Center, Div. of Infectious Disease
Rochester, New York, United States, 14642
AIDS Community Health Center
Rochester, New York, United States, 14642
United States, North Carolina
Duke University School of Medicine; Dept. of Infectious Diseases
Durham, North Carolina, United States, 27710
United States, Ohio
University of Cincinnati Medical Center Holmes Division
Cincinnati, Ohio, United States, 45267
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
Case Western Reserve Univ.
Cleveland, Ohio, United States, 44106-5083
Ohio State University College of Medicine
Columbus, Ohio, United States, 43210
Ohio State University, College of Medicine
Columbus, Ohio, United States, 43210
United States, Virginia
Virginia Commonwealth Univ. Medical Ctr. CRS
Richmond, Virginia, United States, 23219

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

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:

Haga clic aquí para ver información sobre este ensayo clínico en español This link exits the ClinicalTrials.gov site

Click here for more information on recommended immunizations for HIV positive adults This link exits the ClinicalTrials.gov site

Publications:

Maier I, Wu GY. Hepatitis C and HIV co-infection: a review. World J Gastroenterol. 2002 Aug;8(4):577-9. Review.

Rockstroh JK. Management of hepatitis B and C in HIV co-infected patients. J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S59-65. Review.

Sulkowski MS, Mast EE, Seeff LB, Thomas DL. Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clin Infect Dis. 2000 Apr;30 Suppl 1:S77-84. Review.

Responsible Party:	Rona Siskind, DAIDS
ClinicalTrials.gov Identifier:	NCT00393276 History of Changes
Other Study ID Numbers:	ACTG A5232, 1R21AI066957-01
Study First Received:	October 25, 2006
Last Updated:	January 26, 2012
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:

HIV Infections
Acquired Immunodeficiency Syndrome
Hepatitis
Hepatitis A
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
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on February 09, 2012