HOPE in Action Liver Transplantation From Donors With HIV: Impact on Opportunistic Infections, Cancer, and Long-Term Outcomes (Expanding HOPE Liver) (RTB-024)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Incidence of a composite event of opportunistic infection or cancer in Human Immunodeficiency Virus (HIV)-infected donor (HIV D+)/recipient (R+) compared with HIV-uninfected donor (HIV D-)/recipient (R+) liver transplant recipients
研究概览
简要总结
This is a prospective, multicenter clinical study. The objective is to determine whether a liver transplant from a deceased donor with HIV is associated with an increased risk of opportunistic infection and cancer. Adults with Human Immunodeficiency Virus (HIV) in need of a liver or simultaneous liver-kidney (SLK) transplant who meet study-specified criteria will be offered enrollment in the study. The analytic plan includes an observational cohort of liver and SLK transplant recipients from prior HOPE in Action studies.
详细描述
This is a prospective, multicenter observational study of liver transplantation from deceased donors with Human Immunodeficiency Virus (HIV) to recipients with HIV. The primary objective is to determine whether liver transplantation (LT) from donors with HIV to recipients with HIV (HIV D+/R+) is associated with an increased risk of opportunistic infections or cancer compared with LT from donors without HIV to recipients with HIV (HIV D-/R+).
Adults with HIV who require a liver transplant or simultaneous liver-kidney (SLK) transplant and meet study eligibility criteria will be enrolled. Participants who receive a liver or SLK transplant from a donor with HIV will be assigned to the HIV D+/R+ cohort. Participants who receive a liver or SLK transplant from a donor without HIV, including donors with suspected false-positive HIV screening tests that are subsequently confirmed HIV negative, will be assigned to the HIV D-/R+ cohort. Participants will be followed for a minimum of 6 months and up to 4 years post-transplant.
To improve precision in estimating the association between donor HIV status and the risk of opportunistic infection or cancer, analyses will incorporate observational cohorts from prior HOPE in Action liver transplantation studies, including the HOPE Liver Pilot Study, HOPE Liver U01 (RTB-009), and the HOPE Liver Long-Term Follow-Up (LLTF) Study, where appropriate. In addition to clinical outcomes, biospecimens will be collected to investigate virologic and immunologic mechanisms that may contribute to infection and cancer risk following transplantation from donors with HIV.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recipient Inclusion Criteria
- •Participant meets local criteria for liver or simultaneous liver kidney (SLK) transplant
- •Participant or legally authorized representative (in accordance with Johns Hopkins Medicine Institutional Review Board (IRB) and local IRB policy) is able to understand and provide informed consent
- •Participant has documented HIV infection by any licensed assay or documented history of detectable Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA)
- •Participant is ≥ 18 years old
- •Most recent HIV-1 RNA <= 50 copies RNA/mL. Viral blips between 50-400 copies will be allowed as long as there are not consecutive measurements > 200 copies/mL. Organ recipients who are unable to tolerate ART due to organ failure or recently started ART may have detectable viral load and still be eligible if a safe and effective antiretroviral regimen to be used by the recipient after transplantation is described
- •Deceased Donor Criteria
- •Donation after brain death or cardiac death
- •Donors with HIV have confirmed or suspected HIV infection (by medical record history and licensed HIV test). If HIV infection is diagnosed during the donor evaluation process, a second confirmatory test will be required. Organs from donors with suspected false positive HIV screening tests can be used under this protocol
- •Donor has no active opportunistic infections, neoplasms, and/or severe acute retroviral syndrome; if previous history of an opportunistic infection, donor has received appropriate treatment
- •Donor may have any HIV-1 RNA viral load provided a safe, tolerable, and effective post-transplant antiretroviral regimen to be prescribed for the recipient is anticipated, described, and justified
- •Donors with active hepatitis C virus infection (detectable HCV nucleic acid by licensed assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified lab) are acceptable based on local site practice
排除标准
- •Participant has prior progressive multifocal leukoencephalopathy (PML), cryptosporidiosis of > 1 month, or primary Central Nervous System (CNS) lymphoma
- •Participant is pregnant or breastfeeding. Note: Participants who become pregnant post-transplant will be followed on study and managed per local site practice
- •Past or current medical problems or findings from medical history, physical examination, or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
研究组 & 干预措施
HIV D-/R+ Arm
Participants who receive a liver or SLK from a donor without HIV (D-) will be in this arm. Participants who accept an HIV suspected false positive (FP) organ will be part of the D-/R+ arm once confirmatory testing confirms the negative HIV status of the donor. Participants will be followed for a minimum of 6 months and up to 4 years post-transplant
HIV D+/R+ Arm
Prospective cohort of transplant recipients who receive a liver or SLK from a donor with HIV (D+) will be in the HIV D+/R+ arm. Participants will be followed for a minimum of 6 months and up to 4 years post-transplant
结局指标
主要结局
Incidence of a composite event of opportunistic infection or cancer in Human Immunodeficiency Virus (HIV)-infected donor (HIV D+)/recipient (R+) compared with HIV-uninfected donor (HIV D-)/recipient (R+) liver transplant recipients
时间窗: From transplant through 4 years post-transplant
次要结局
- Serious adverse events post-transplant(From transplant through 4 years post-transplant)
- Incidence of rejection events post-transplant(From transplant through 4 years post-transplant)
- Overall survival measured as time from transplantation to death from any cause(From transplant through 4 years post-transplant)
- Graft survival measured as time from transplantation to graft failure(From transplant through 4 years post-transplant)
- Incidence of bacterial infections post-transplant(From transplant through 4 years post-transplant)
- Incidence of post-transplant cancer(From transplant through 4 years post-transplant)
- Type of post-transplant cancer(From transplant through 4 years post-transplant)
- Graft function over time as assessed by Fibrosis-4 (FIB-4) Index(From transplant through 4 years post-transplant)
- Graft function over time as assessed by AST to Platelet Ratio Index (APRI)(From transplant through 4 years post-transplant)
- Incidence of Human Immunodeficiency Virus (HIV)-breakthrough post-transplant(From transplant through 4 years post-transplant)
- Incidence of Human Immunodeficiency Virus (HIV) persistent virologic failure post-transplant(From transplant through 4 years post-transplant)
- Incidence of new antiretroviral drug resistance and/or X4 tropic virus post-transplant(From transplant through 4 years post-transplant)
- Incidence of surgical transplant complications(During the first year post-transplant)
- Incidence of vascular transplant complications(During the first year post-transplant)
- Number of Participants with Positive Kaposi Sarcoma Herpesvirus (KSHV) serology(From transplant through 4 years post-transplant)
- Kaposi Sarcoma Herpesvirus (KSHV) Polymerase Chain Reaction (PCR) over time(From transplant through 4 years post-transplant)
- Incidence of fungal infections post-transplant(From transplant through 4 years post-transplant)
- Incidence of viral infections post-transplant(From transplant through 4 years post-transplant)
- Incidence of other opportunistic infections post-transplant(From transplant through 4 years post-transplant)