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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HIV Infections, Hepatitis C

Intervention / Treatment
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* Biological: Twinrix
* Biological: Decavac


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>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<br>* Combined hepatitis A and hepatitis B immunization<br>Biological: Decavac<br>* Diphtheria and tetanus toxoid vaccine<br>|
| Experimental: B<br>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<br>* Combined hepatitis A and hepatitis B immunization<br>Biological: Decavac<br>* Diphtheria and tetanus toxoid vaccine<br>|
| Experimental: C<br>HCV/HIV-coinfected as defined above in Arms A and B. | Biological: Twinrix<br>* Combined hepatitis A and hepatitis B immunization<br>Biological: Decavac<br>* Diphtheria and tetanus toxoid vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Experienced, Treatment Naive, Immunizations