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

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.

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