Expanding HOPE Liver

National Institute of Allergy and Infectious Diseases (NIAID)80 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: Recipient Inclusion Criteria 1. Participant meets local criteria for liver or simultaneous liver kidney (SLK) transplant 2. 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 3. Participant has documented HIV infection by any licensed assay or documented history of detectable Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) 4. Participant is ≥ 18 years old 5. 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 1. Donation after brain death or cardiac death 2. 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 3. 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 4. 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 5. 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 Exclusion Criteria: Recipient 1. Participant has prior progressive multifocal leukoencephalopathy (PML), cryptosporidiosis of \> 1 month, or primary Central Nervous System (CNS) lymphoma 2. Participant is pregnant or breastfeeding. Note: Participants who become pregnant post-transplant will be followed on study and managed per local site practice 3. 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

Outcomes

Primary Outcomes

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

Time frame: From transplant through 4 years post-transplant

Secondary Outcomes

Overall survival measured as time from transplantation to death from any cause

Time frame: From transplant through 4 years post-transplant

Graft survival measured as time from transplantation to graft failure

Graft failure is defined as any of the following events: re-transplantation; death; allograft nephrectomy; initiation of post-donation chronic dialysis (SLK only).

Time frame: From transplant through 4 years post-transplant

Incidence of bacterial infections post-transplant

Time frame: From transplant through 4 years post-transplant

Incidence of post-transplant cancer

As determined by local pathology

Time frame: From transplant through 4 years post-transplant

Type of post-transplant cancer

As determined by local pathology

Time frame: From transplant through 4 years post-transplant

Serious adverse events post-transplant

Time frame: From transplant through 4 years post-transplant

Incidence of rejection events post-transplant

Time frame: From transplant through 4 years post-transplant

Graft function over time as assessed by Fibrosis-4 (FIB-4) Index

Graft function will be assessed over time using the Fibrosis-4 (FIB-4) Index. FIB-4 is calculated using age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. Higher FIB-4 values are associated with a greater likelihood of liver fibrosis.

Time frame: From transplant through 4 years post-transplant

Graft function over time as assessed by AST to Platelet Ratio Index (APRI)

Graft function will be assessed over time using the Aspartate Aminotransferase (AST) to Platelet Ratio Index (APRI). APRI is calculated using AST level, the upper limit of normal for AST, and platelet count. Higher APRI values are associated with a greater likelihood of liver fibrosis.

Time frame: From transplant through 4 years post-transplant

Incidence of Human Immunodeficiency Virus (HIV)-breakthrough post-transplant

Time frame: From transplant through 4 years post-transplant

Incidence of Human Immunodeficiency Virus (HIV) persistent virologic failure post-transplant

Time frame: From transplant through 4 years post-transplant

Incidence of new antiretroviral drug resistance and/or X4 tropic virus post-transplant

Time frame: From transplant through 4 years post-transplant

Incidence of surgical transplant complications

Time frame: During the first year post-transplant

Incidence of vascular transplant complications

Time frame: During the first year post-transplant

Number of Participants with Positive Kaposi Sarcoma Herpesvirus (KSHV) serology

KSHV serostatus will be assessed using serologic testing for antibodies to KSHV. Participants will be classified as KSHV seropositive or seronegative based on the specified laboratory assay.

Time frame: From transplant through 4 years post-transplant

Kaposi Sarcoma Herpesvirus (KSHV) Polymerase Chain Reaction (PCR) over time

Time frame: From transplant through 4 years post-transplant

Incidence of fungal infections post-transplant

Time frame: From transplant through 4 years post-transplant

Incidence of viral infections post-transplant

Time frame: From transplant through 4 years post-transplant

Incidence of other opportunistic infections post-transplant

Time frame: From transplant through 4 years post-transplant

Expanding HOPE Liver

Overview

Conditions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes