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NCT Number: NCT03734393

HOPE in Action Trial of HIV+ Deceased Donor Liver Transplants for HIV+ Recipients

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

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Key information

Conditions

HIV Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Alabama, Birmingham, Birmingham, Alabama, United States

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

HIVD+/R+

Other

Liver from an HIV-infected deceased donor

Primary outcomes

  1. Time to first death or graft failure or serious adverse event (SAE) or HIV breakthrough or opportunistic infection as a composite measure

    Time frame: 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 outcomes

  1. Time to Pre-transplant mortality

    Time frame: 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)

  2. Graft Failure as assessed by Time to first occurrence of mortality or re-transplant or return to maintenance dialysis

    Time frame: 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)

  3. 1-year acute liver rejection

    Time frame: 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.

  4. 2-year acute liver rejection

    Time frame: 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.

  5. 3-year acute liver rejection

    Time frame: 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.

  6. Number of graft rejections in liver transplant

    Time frame: 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.

  7. 6-month acute kidney rejection in simultaneous liver/kidney transplant recipients

    Time frame: 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)

  8. 1-year acute kidney rejection in simultaneous liver/kidney transplant recipients only

    Time frame: 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)

  9. Number of Non-alcoholic fatty liver (NAFL)

    Time frame: 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

  10. Number of steatohepatitis (NASH)

    Time frame: 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

  11. Trajectory of recipient Cluster of Differentiation (CD4) count over time

    Time frame: From date of transplant through end of follow up, up to 4 years

    Analysis of repeated measures of CD4 (cells/mm3) count (longitudinal model)

  12. Trajectory of recipient plasma HIV RNA over time

    Time frame: 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

  13. Graft function as assessed by Fibrosis-4 index

    Time frame: 1 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.

  14. Graft function as assessed by Fibrosis-4 index

    Time frame: 2 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.

  15. Graft function as assessed by Fibrosis-4 index

    Time frame: 3 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.

  16. Graft function as assessed by Fibrosis-4 index

    Time frame: 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.

  17. Graft function as assessed by incidence of fibrosis

    Time frame: 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).

  18. Graft function as assessed by liver stiffness

    Time frame: 1 year post-transplant

    Mean calculated liver stiffness by transient elastography (kPA)

  19. Graft function as assessed by liver stiffness

    Time frame: 2 years post-transplant

    Mean calculated liver stiffness by transient elastography (kPA)

  20. Graft function as assessed by liver stiffness

    Time frame: 3 years post-transplant

    Mean calculated liver stiffness by transient elastography (kPA)

  21. Average graft function as assessed by aspartate aminotransferase (AST)

    Time frame: 1 year post-transplant

    Mean calculated AST (U/L)

  22. Average graft function as assessed by AST

    Time frame: 2 years post-transplant

    Mean calculated AST (U/L)

  23. Average graft function as assessed by AST

    Time frame: 3 years post-transplant

    Mean calculated AST (U/L)

  24. Average graft function as assessed by AST

    Time frame: 4 years post-transplant

    Mean calculated AST (U/L)

  25. Average graft function as assessed by alanine aminotransferase (ALT)

    Time frame: 1 year post-transplant

    Mean calculated ALT (U/L)

  26. Average graft function as assessed by ALT

    Time frame: 2 years post-transplant

    Mean calculated ALT (U/L)

  27. Average Graft function as assessed by ALT

    Time frame: 3 years post-transplant

    Mean calculated ALT (U/L)

  28. Average graft function as assessed by ALT

    Time frame: 4 years post-transplant

    Mean calculated ALT (U/L)

  29. Average graft function as assessed by bilirubin

    Time frame: 1 year post-transplant

    Mean calculated bilirubin (mg/dL)

  30. Average graft function as assessed by bilirubin

    Time frame: 2 years post-transplant

    Mean calculated bilirubin (mg/dL)

  31. Average graft function as assessed by bilirubin

    Time frame: 3 years post-transplant

    Mean calculated bilirubin (mg/dL)

  32. Average graft function as assessed by Bilirubin

    Time frame: 4 years post-transplant

    Mean calculated bilirubin (mg/dL)

  33. Graft function as assessed by Mean calculated Model for End Stage Liver Disease (MELD) score

    Time frame: 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

  34. Graft function as assessed by Mean calculated MELD score

    Time frame: 2 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

  35. Graft function as assessed by Mean calculated MELD score

    Time frame: 3 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

  36. Graft function as assessed by Mean calculated MELD score

    Time frame: 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

  37. Graft function as assessed by AST to Platelet Ratio (APRI) index

    Time frame: 1 year post-transplant

    Mean calculated APRI index [( AST / upper limits of normal (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.

  38. Graft function as assessed by AST to Platelet Ratio (APRI) index

    Time frame: 2 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.

  39. Graft function as assessed by AST to Platelet Ratio (APRI) index

    Time frame: 3 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.

  40. Graft function as assessed by AST to Platelet Ratio (APRI) index

    Time frame: 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.

  41. Metabolic Outcome as assessed by Body mass index (BMI)

    Time frame: 1 year post-transplant

    Mean calculated BMI (weight in kilograms/height in meters squared)

  42. Metabolic Outcome as assessed by Body mass index (BMI)

    Time frame: 2 years post-transplant

    Mean calculated BMI(weight in kilograms/height in meters squared)

  43. Metabolic Outcome as assessed by Body mass index (BMI)

    Time frame: 3 years post-transplant

    Mean calculated BMI(weight in kilograms/height in meters squared)

  44. Metabolic Outcome as assessed by Body mass index (BMI)

    Time frame: 4 years post-transplant

    Mean calculated BMI(weight in kilograms/height in meters squared)

  45. Average hemoglobin a1c among participants at 1 year

    Time frame: 1 years post-transplant

    Mean calculated hemoglobin a1c (mg/dL)

  46. Average hemoglobin a1c among participants at 2 years

    Time frame: 2 years post-transplant

    Mean calculated hemoglobin a1c (mg/dL)

  47. Average hemoglobin a1c among participants at 3 years

    Time frame: 3 years post-transplant

    Mean calculated hemoglobin a1c (mg/dL)

  48. Average hemoglobin a1c among participants at 4 years

    Time frame: 4 years post-transplant

    Mean calculated hemoglobin a1c (mg/dL)

  49. Number of HIV breakthroughs

    Time frame: 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

  50. Number of opportunistic infections

    Time frame: From date of transplant through end of follow-up, up to 4 years

    Cumulative incidence of opportunistic infections

  51. Number of X4 tropic virus breakthroughs

    Time frame: 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

  52. Number of vascular complications

    Time frame: From date of transplant through year 1

    Number of vascular complications within 1 year of transplant, e.g. thrombosis, aneurysm

  53. Number of surgical complications

    Time frame: From date of transplant through year 1

    Number of surgical complications within 1 year of transplant, e.g. delayed closure, wound dehiscence

  54. Number of viral-related malignancies

    Time frame: From date of transplant through end of follow-up, up to 4 years

    Number of malignancies as determined by local pathology

  55. Hepatitis C (HCV) sustained viral response post-transplant

    Time frame: 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

  56. Number of the formation of de novo donor-specific human leukocyte antigen(HLA) antibodies

    Time frame: 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

  57. 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

    Time frame: 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

Sponsors and collaborators

Lead sponsor

Johns Hopkins University

Other

Collaborators

  • National Institute of Allergy and Infectious Diseases (NIAID)

Registry information

Official study title

HOPE in Action Prospective Multicenter, Clinical Trial of HIV+ Deceased Donor Liver Transplants for HIV+ Recipients

Important dates

Study start
2019
Primary completion
2025
Study completion
2025
First posted
Nov 8, 2018
Registry last updated
Jul 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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