Optimizing Vaccine Responsiveness in HIV-1 and HCV Infections by Identifying Determinants of Responsiveness: A Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 12
- 主要终点
- B-cell humoral responses
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
C
HCV/HIV-coinfected as defined above in Arms A and B.
干预措施: Decavac (Biological)
C
HCV/HIV-coinfected as defined above in Arms A and B.
干预措施: Twinrix (Biological)
B
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.
干预措施: Decavac (Biological)
B
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.
干预措施: Twinrix (Biological)
A
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.
干预措施: Decavac (Biological)
A
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.
干预措施: Twinrix (Biological)
结局指标
主要结局
B-cell humoral responses
时间窗: At Week 8
T-cell responses as reflected by hepatitis B and tetanus antibody titers
时间窗: At Week 8
Dendritic cell, B-cell, and T-cell functional markers
时间窗: At Study Entry
次要结局
- T-cell responses to hepatitis A, hepatitis B, and tetanus antigens(At Weeks 3 and 8)
- B-cell functional marker(At Week 6)
- 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)