HOPE in Action Trial of HIV+ Deceased Donor Liver Transplants for HIV+ Recipients
- Conditions
- Hiv
- Interventions
- Other: HIVD+/R+
- Registration Number
- NCT03734393
- Lead Sponsor
- Johns Hopkins University
- Brief Summary
The primary objective of this study is to determine if an HIV-infected donor liver (HIVD+) transplant is safe with regards to major transplant-related and HIV-related complications
- Detailed Description
This study will evaluate if receiving a liver transplant from an HIV-infected deceased liver donor is safe with regards to survival and major transplant-related and HIV-related complications compared to receiving a liver from an HIV-uninfected deceased liver donor (HIVD-). Those participants who have accepted an HIVD- organ will be randomized to be followed in the full study or followed in the nested observational group
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 80
- Participant meets the standard criteria for liver transplant at the local center.
- Participants being listed for a simultaneous liver kidney (SLK) are eligible if participants meet the standard criteria for both organs.
- Participant is able to understand and provide informed consent.
- Participant meets with an independent advocate per the HIV Organ Policy Equity (HOPE) Act Safeguards and Research Criteria.
- Documented HIV infection (by any licensed assay or documented history of detectable HIV-1 RNA).*
- Participant is ≥ 18 years old.
- Opportunistic complications: prior history of certain opportunistic infections is not an exclusion if the participant has received appropriate therapy and has no evidence of active disease. Medical record documentation should be provided whenever possible.
- CD4+ T-cell count: ≥ 100/µL within 16 weeks prior to transplant if no history of AIDS-defining infection; or ≥ 200 μL if history of opportunistic infection is present.
- HIV-1 RNA is below 50 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 anti-retroviral therapy (ART) due to organ.
failure or recently started ART may be eligible despite a detectable viral load if safe and effective ART to be used by the recipient after transplantation is described.
- Participant must have or be willing to start seeing a primary medical care provider with expertise in HIV management.
- Participant is willing to comply with all medications related to participant's transplant and HIV management.
- For participants with a history of aspergillus colonization or disease, no current clinical evidence of active disease.
- Agreement to use contraception.
- Participant is not suffering from significant wasting (e.g. body mass index < 21) thought to be related to HIV disease.
- Participant has a history of progressive multifocal leukoencephalopathy (PML), or primary central nervous system (CNS) lymphoma.*
- Participant is pregnant or breastfeeding. (Note: Participants who become pregnant post-transplant will continue to be followed in the study and will be managed per local site practice. Women that become pregnant should not breastfeed.)
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description HIV D+/R+ HIVD+/R+ HIV-infected individuals that accept an organ from an HIV-infected deceased donor - enrollment 40
- Primary Outcome Measures
Name Time Method Time to first death or graft failure or serious adverse event (SAE) or HIV breakthrough or opportunistic infection as a composite measure From date of transplant through administrative censorship at study completion, up to 4 years Time (in days) to first of any of the following events: death or graft failure or SAE or HIV breakthrough or opportunistic infection
- Secondary Outcome Measures
Name Time Method 3-year acute liver rejection From date of transplant to end of year 3 Proportion of recipients who experience acute rejection as measured by biopsy using Banff 2016 comprehensive Update for antibody mediated rejection and Banff 1997 criteria for acute cellular rejection, liver.
Number of Non-alcoholic fatty liver (NAFL) From date of transplant through end of follow-up, up to 3 years Cumulative incidence of NAFL as measured by biopsy and transient elastography with controlled attenuation parameter for steatosis
Trajectory of recipient Cluster of Differentiation (CD4) count over time From date of transplant through end of follow up, up to 4 years Analysis of repeated measures of CD4 (cells/mm3) count (longitudinal model)
2-year acute liver rejection From date of transplant to end of year 2 Proportion of recipients who experience acute rejection as measured by biopsy using Banff 2016 comprehensive Update for antibody mediated rejection and Banff 1997 criteria for acute cellular rejection, liver.
Number of graft rejections in liver transplant From date of transplant to end of year 3 Cumulative incidence of acute rejection (survival framework) as measured by biopsy using Banff 2016 comprehensive Update for antibody mediated rejection and Banff 1997 criteria for acute cellular rejection, liver.
Graft Failure as assessed by Time to first occurrence of mortality or re-transplant or return to maintenance dialysis From date of transplant through administrative censorship at study completion, up to 4 years Time (in days) to mortality or re-transplant or return to maintenance dialysis (survival framework)
1-year acute kidney rejection in simultaneous liver/kidney transplant recipients only From date of transplant to end of year 1 Proportion of recipients who experience acute rejection as measured by biopsy using Banff 2015 criteria: Borderline changes: 'Suspicious' for acute T-cell mediated rejection.This category is used when no intimal arteritis is present, but there are foci of mild tubulitis (t1, t2, or t3) with minor interstitial infiltration (i0 or i1) or interstitial infiltration (i2, i3) with mild (t1) tubulitis. Acute T-cell mediated rejection:Grade from IA defined as cases with significant interstitial infiltration (\>25% of parenchyma affected, i2 or i3) and foci of moderate tubulitis (t2) to III defined as cases with 'transmural' arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3)
Trajectory of recipient plasma HIV RNA over time From date of transplant through end of follow-up, up to 4 years Analysis of repeated measures of plasma HIV RNA (copies/mL) longitudinal model
Time to Pre-transplant mortality From date of enrollment to date of transplant or death of any cause, whichever comes first, assessed up to 4 years Time (in days) to mortality while enrolled before transplant (survival framework)
Average graft function as assessed by aspartate aminotransferase (AST) 1 year post-transplant Mean calculated AST (U/L)
Graft function as assessed by liver stiffness 3 years post-transplant Mean calculated liver stiffness by transient elastography (kPA)
Graft function as assessed by Fibrosis-4 index 4 years post-transplant Mean calculated fibrosis-4 index (Age (years) + AST/platelet count (109/L) x √ALT) Fibrosis 4 index estimates the amount of scar or fibrosis in the liver without requiring a biopsy. Using a lower cutoff value of 1.45, a Fibrosis-4 score \<1.45 had a negative predictive value of 90% for advanced fibrosis. In contrast, a Fibrosis-4 \>3.25 would have a 97% specificity and a positive predictive value of 65% for advanced fibrosis. In the patient cohort in which this formula was first validated, at least 70% patients had values \<1.45 or \>3.25.
Average graft function as assessed by AST 4 years post-transplant Mean calculated AST (U/L)
1-year acute liver rejection From date of transplant to end of year 1 Proportion of recipients who experience acute rejection as measured by biopsy using Banff 2016 comprehensive Update for antibody mediated rejection and Banff 1997 criteria for acute cellular rejection, liver.
Number of steatohepatitis (NASH) From date of transplant through end of follow-up, up to 3 years Cumulative incidence of NASH as measured by biopsy and transient elastography with controlled attenuation parameter for steatosis
Average graft function as assessed by alanine aminotransferase (ALT) 1 year post-transplant Mean calculated ALT (U/L)
Average graft function as assessed by bilirubin 3 years post-transplant Mean calculated bilirubin (mg/dL)
Number of surgical complications From date of transplant through year 1 Number of surgical complications within 1 year of transplant, e.g. delayed closure, wound dehiscence
6-month acute kidney rejection in simultaneous liver/kidney transplant recipients From date of transplant to 6 months post transplant Proportion of recipients who experience acute rejection as measured by biopsy using Banff 2015 criteria: Borderline changes: 'Suspicious' for acute T-cell mediated rejection.This category is used when no intimal arteritis is present, but there are foci of mild tubulitis (t1, t2, or t3) with minor interstitial infiltration (i0 or i1) or interstitial infiltration (i2, i3) with mild (t1) tubulitis. Acute T-cell mediated rejection:Grade from IA defined as cases with significant interstitial infiltration (\>25% of parenchyma affected, i2 or i3) and foci of moderate tubulitis (t2) to III defined as cases with 'transmural' arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3)
Graft function as assessed by incidence of fibrosis From date of transplant through end of follow-up, up to 3 years Cumulative incidence of advanced fibrosis (stage F3 or greater as defined by metavir fibrosis score) as measured on biopsy. The fibrosis score is assessed on a five point scale (F0 = no fibrosis, F1 = portal fibrosis without septa, F2 = few septa, F3 = numerous septa without cirrhosis, F4 = cirrhosis).
Average hemoglobin a1c among participants at 3 years 3 years post-transplant Mean calculated hemoglobin a1c (mg/dL)
Number of opportunistic infections From date of transplant through end of follow-up, up to 4 years Cumulative incidence of opportunistic infections
Graft function as assessed by Mean calculated Model for End Stage Liver Disease (MELD) score 1 year post-transplant Mean calculated MELD score. MELD score indicates the severity of liver disease, with scores ranging from 0-40. The higher the score the more severe the disease
Average hemoglobin a1c among participants at 4 years 4 years post-transplant Mean calculated hemoglobin a1c (mg/dL)
Hepatitis C (HCV) sustained viral response post-transplant 12 weeks HCV treatment Proportion of HCV RNA positive recipients that achieve a sustained virologic response week 12 post-treatment (\<15 IU/mL) with direct acting antivirals
Average Graft function as assessed by ALT 3 years post-transplant Mean calculated ALT (U/L)
Average graft function as assessed by Bilirubin 4 years post-transplant Mean calculated bilirubin (mg/dL)
Graft function as assessed by AST to Platelet Ratio (APRI) index 4 years post-transplant Mean calculated APRI index \[( AST / ULN AST ) x 100\] / Platelets (109/L)\] An APRI score greater than 1.0 has a sensitivity of 76% and specificity of 72% for predicting cirrhosis. In addition, APRI score greater than 0.7 has a sensitivity of 77% and specificity of 72% for predicting significant hepatic fibrosis.For detection of cirrhosis, using an APRI cutoff score of 2.0 is more specific (91%) but less sensitive (46%). The lower the APRI score (less than 0.5), the greater the negative predictive value (and ability to rule out cirrhosis) and the higher the value (greater than 1.5) the greater the positive predictive value (and ability to rule in cirrhosis); midrange values are less helpful.
Average hemoglobin a1c among participants at 1 year 1 years post-transplant Mean calculated hemoglobin a1c (mg/dL)
Average hemoglobin a1c among participants at 2 years 2 years post-transplant Mean calculated hemoglobin a1c (mg/dL)
Number of X4 tropic virus breakthroughs From date of transplant through end of follow-up, up to 4 years Measured by sending virus at time of breakthrough for HIV co-receptor assay
Time to first occurrence of all-cause-mortality or graft failure or renal allograft rejection or HIV breakthrough or HIV virologic failure or AIDS defining illness as a composite measure From date of transplant through end of follow-up, up to 4 years Time to first of any of these events: all-cause-mortality or graft failure or renal allograft rejection or HIV breakthrough or HIV virologic failure or AIDS defining illness
Average graft function as assessed by ALT 4 years post-transplant Mean calculated ALT (U/L)
Graft function as assessed by Mean calculated MELD score 4 years post-transplant Mean calculated MELD score. MELD score indicates the severity of liver disease, with scores ranging from 0-40. The higher the score the more severe the disease
Metabolic Outcome as assessed by Body mass index (BMI) 4 years post-transplant Mean calculated BMI(weight in kilograms/height in meters squared)
Number of HIV breakthroughs From date of transplant through end of follow-up, up to 4 years Measured by local sites' Clinical Laboratory Improvement Amendments (CLIA) certified lab with episode of HIV breakthrough defined as 2 consecutive plasma HIV viral loads \>200 copies/mL or one HIV viral load \>1000 copies/mL after a period of virologic control post-transplant
Number of vascular complications From date of transplant through year 1 Number of vascular complications within 1 year of transplant, e.g. thrombosis, aneurysm
Number of viral-related malignancies From date of transplant through end of follow-up, up to 4 years Number of malignancies as determined by local pathology
Number of the formation of de novo donor-specific human leukocyte antigen(HLA) antibodies From date of transplant through end of year 1 Proportion of participants with a de novo donor-specific HLA antibody as measured and reported by local sites' lab
Trial Locations
- Locations (26)
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
MedStar Georgetown Transplant Institute
🇺🇸Washington, District of Columbia, United States
Emory University
🇺🇸Atlanta, Georgia, United States
University of Maryland, Institute of Human Virology
🇺🇸Baltimore, Maryland, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
New York University School of Medicine
🇺🇸New York, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Tennessee Health and Science Center
🇺🇸Memphis, Tennessee, United States
University of Miami
🇺🇸Miami, Florida, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
UPMC - University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
University of Alabama, Birmingham
🇺🇸Birmingham, Alabama, United States
University of California, San Diego
🇺🇸San Diego, California, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States