Clinical trial NCT00393276: Determining Responses to Two Different Vaccines in HIV and HCV Infected Individuals
Official title: Optimizing Vaccine Responsiveness in HIV-1 and HCV Infections by Identifying Determinants of Responsiveness: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Hepatitis C
Keywords: Treatment Experienced
Treatment Naive
Immunizations
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
First posted: 2006-10-27
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

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 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

Primary outcomes:
measure: B-cell humoral responses
timeFrame: At Week 8
measure: T-cell responses as reflected by hepatitis B and tetanus antibody titers
timeFrame: At Week 8
measure: Dendritic cell, B-cell, and T-cell functional markers
timeFrame: At Study Entry
Secondary outcomes:
measure: B-cell functional marker
timeFrame: At Week 6
measure: T-cell responses to hepatitis A, hepatitis B, and tetanus antigens
timeFrame: At Weeks 3 and 8
measure: Longitudinal serum antibody titers to hepatitis A, hepatitis B, and tetanus (B-cell responses)
timeFrame: At Study Entry and Weeks 1, 3, 6, 8, 12, and 24
measure: CD4/CD8 and HCV genotype
timeFrame: At Study entry
measure: Baseline antibody status for hepatitis B core antigen (anti-HBc)
timeFrame: At Study entry
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UCSD Antiviral Research Center CRS
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Baltimore
country: United States
facility: IHV Baltimore Treatment CRS
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Clinical Research Site (MGH CRS) CRS
state: Massachusetts
city: New York
country: United States
facility: Columbia P&S CRS
state: New York
city: Durham
country: United States
facility: Duke Univ. Med. Ctr. Adult CRS
state: North Carolina
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth CRS
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Dallas
country: United States
facility: Trinity Health and Wellness Center CRS
state: Texas
city: San Juan
country: Puerto Rico
facility: Puerto Rico AIDS Clinical Trials Unit CRS
Study officials:
affiliation: Case Western Reserve University
name: Donald D. Anthony, MD, PhD
role: STUDY_CHAIR
affiliation: Division of Infectious Diseases, University Hospital of Cleveland
name: Benigno Rodriguez, MD
role: STUDY_CHAIR
References:
citation: Maier I, Wu GY. Hepatitis C and HIV co-infection: a review. World J Gastroenterol. 2002 Aug;8(4):577-9. doi: 10.3748/wjg.v8.i4.577.
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. doi: 10.1097/00126334-200309011-00009.
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. doi: 10.1086/313842.