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

HIV Infections Clinical Trial

Official title:

Optimizing Vaccine Responsiveness in HIV-1 and HCV Infections by Identifying Determinants of Responsiveness: A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00393276
• Other study ID #: A5232
• Secondary ID: 101541R21AI06695
• Status: Completed
• Phase: Phase 1
• Start date: August 2007
• Est. completion date: July 2009

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis C
• HIV Infections
• Infections

Intervention

Biological:
• Twinrix
Combined hepatitis A and hepatitis B immunization
• Decavac
Diphtheria and tetanus toxoid vaccine

Locations

Country	Name	City	State
Puerto Rico	Puerto Rico AIDS Clinical Trials Unit CRS	San Juan
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	IHV Baltimore Treatment CRS	Baltimore	Maryland
United States	Massachusetts General Hospital Clinical Research Site (MGH CRS) CRS	Boston	Massachusetts
United States	Case CRS	Cleveland	Ohio
United States	MetroHealth CRS	Cleveland	Ohio
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	Trinity Health and Wellness Center CRS	Dallas	Texas
United States	Duke Univ. Med. Ctr. Adult CRS	Durham	North Carolina
United States	Columbia P&S CRS	New York	New York
United States	UCSD Antiviral Research Center CRS	San Diego	California
United States	Ucsf Aids Crs	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	AIDS Clinical Trials Group

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (3)

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

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	B-cell humoral responses		At Week 8
Primary	T-cell responses as reflected by hepatitis B and tetanus antibody titers		At Week 8
Primary	Dendritic cell, B-cell, and T-cell functional markers		At Study Entry
Secondary	B-cell functional marker		At Week 6
Secondary	T-cell responses to hepatitis A, hepatitis B, and tetanus antigens		At Weeks 3 and 8
Secondary	Longitudinal serum antibody titers to hepatitis A, hepatitis B, and tetanus (B-cell responses)		At Study Entry and Weeks 1, 3, 6, 8, 12, and 24
Secondary	CD4/CD8 and HCV genotype		At Study entry
Secondary	Baseline antibody status for hepatitis B core antigen (anti-HBc)		At Study entry

External Links

•   Click here for more information on recommended immunizations for HIV positive adults
•   Haga clic aquí para ver información sobre este ensayo clínico en español