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

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Adult 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

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

Drug Information available for: Tetanus Vaccine Hepatitis B Vaccines Hepatitis A Vaccines Twinrix

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title:	Optimizing Vaccine Responsiveness in HIV-1 and HCV Infections by Identifying Determinants of Responsiveness: A Pilot Study

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
Estimated Study Completion Date:	December 2008
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental 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
B: Experimental 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
C: Experimental 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	Recruiting
San Diego, California, United States, 90502
Contact: Jill Kunkel, RN 619-543-8080 jkunkel@ucsd.edu
Principal Investigator: Constance A Benson, MD
UCSF PHP, San Francisco Gen. Hospital	Recruiting
San Francisco, California, United States, 94110
Contact: Michele Downing, RN, BSN. 415-514-0550 ext 354 mdowning@php.ucsf.edu
Principal Investigator: Diane Havlir, MD
United States, Maryland
Johns Hopkins School of Medicine, ACTU	Recruiting
Baltimore, Maryland, United States, 21287-8106
Contact: Ilene P Wiggins, RN 410-614-2766 imp@jhmi.edu
Principal Investigator: Charles Flexner, MD
Univ. of Maryland Biotechnology Institute, Institue of Human Virology	Recruiting
Baltimore, Maryland, United States, 21201
Contact: Sandy Zaremba, RN, CCRC 410-706-1476 zaremba@umbi.umd.edu
Principal Investigator: Robert R Redfield, MD
United States, Massachusetts
Massachusetts General Hospital, Division of Infectious Diseases	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Teri Flynn, RN, ANP 617-724-0072 tflynn@partners.org
Principal Investigator: Daniel R. Kuritzkes, MD
Brigham and Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jon Gothing, RN, BSN 617-732-5635 jgothing@partners.org
Principal Investigator: Paul E. Sax, MD
United States, Missouri
Washington University School of Medicine	Recruiting
St. Louis, Missouri, United States, 63108
Contact: Michael Klebert, R.N.-C., M.S.N. 314-454-0058 mklebert@im.wustl.edu
Principal Investigator: David B. Clifford, MD
United States, New York
Columbia University HIV Prevention and Treatment Research Group	Not yet recruiting
New York, New York, United States, 10032-3784
Contact: Mykyelle Crawford, RN, BSN 212-305-2665 mc675@columbia.edu
Principal Investigator: Scott Hammer, MD
University of Rochester Medical Center, Div. of Infectious Disease	Recruiting
Rochester, New York, United States, 14642
Contact: Carol Greisberger, RN, BS 585-275-2740 carol_greisberger@urmc.rochester.edu
Principal Investigator: Richard C Reichman, MD
AIDS Community Health Center	Recruiting
Rochester, New York, United States, 14642
Contact: Carol Gresiberger, RN, BS 585-275-2740 carol_greisberger@urmc.rochester.edu
Principal Investigator: Richard C Reichman, MD
United States, North Carolina
Duke University School of Medicine; Dept. of Infectious Diseases	Recruiting
Durham, North Carolina, United States, 27710
Contact: Sarah Patillo, BS sara.patillo@duke.edu
Principal Investigator: John A. Bartlett, MD
United States, Ohio
Case Western Reserve Univ.	Recruiting
Cleveland, Ohio, United States, 44106-5083
Contact: Jane Baum, BSN, RN 216-844-2546 baum.jane@clevelandactu.org
Ohio State University, College of Medicine	Recruiting
Columbus, Ohio, United States, 43210
Contact: Todd L. Lusch, BA 614-293-5282 lusch-1@medctr.osu.edu
Principal Investigator: Susan L. Koletar, MD
University of Cincinnati Medical Center Holmes Division	Not yet recruiting
Cincinnati, Ohio, United States, 45267
Contact: Tammy Powell, RN 513-584-8373 powelltm@email.uc.edu
Principal Investigator: Judith Feinberg, MD
Ohio State University College of Medicine	Recruiting
Columbus, Ohio, United States, 43210
Contact: Todd L Lusch, BA 614-293-8112 lusch-1@medctr.osu.edu
Principal Investigator: Susan L Koletar, MD
MetroHealth Medical Center	Recruiting
Cleveland, Ohio, United States, 44109
Contact: Ann Conrad, RN, ACRN 216-778-5489 aconrad@metrohealth.org
Principal Investigator: Robert Kalayjian, MD

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Adult 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

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:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5232, 1-R21-AI066957-01
Study First Received:	October 25, 2006
Last Updated:	September 24, 2008
ClinicalTrials.gov Identifier:	NCT00393276
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Treatment Experienced
Treatment Naive
Immunizations

Study placed in the following topic categories:

Virus Diseases
Hepatitis
Liver Diseases
Sexually Transmitted Diseases, Viral
Digestive System Diseases
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Hepatitis, Viral, Human
Hepatitis C
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Communicable Diseases
RNA Virus Infections
Slow Virus Diseases
Flaviviridae Infections

Immune System Diseases
Lentivirus Infections
Infection

ClinicalTrials.gov processed this record on January 14, 2009