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Completed

NCT Number: NCT03500315

HOPE in Action Prospective Multicenter, Clinical Trial of Deceased HIVD+ Kidney Transplants for HIV+ Recipients

The primary objective of this study is to determine if an HIV-infected deceased kidney donor (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 at Birmingham, Birmingham, Alabama, United States

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About this study

This study will evaluate if receiving a kidney transplant from an HIV-infected deceased kidney donor is safe with regards to survival and major transplant-related and HIV-related complications compared to receiving a kidney from an HIV-uninfected deceased kidney 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 kidney transplant at the local center.
  • Participant is able to understand and provide informed consent.
  • Participant meets with an independent advocate per the HIV Organ Policy Equity (HOPE) Act Safeguards.
  • Documented HIV infection (by any licensed assay, or documented history of detectable HIV-1 RNA).
  • Participant is ≥18 years old.
  • Opportunistic complications: if prior history of an opportunistic infection, the participant has received appropriate therapy and has no evidence of active disease.
  • Cluster of Differentiation 4 (CD4)+ T-cell: ≥200/µL within 16 weeks of transplant.
  • HIV-1 is below 50 copies RNA/mL. Viral blips between 50-400 copies allowed as long as there are not consecutive measurements >200 copies/mL.
  • Participant is willing to comply with all medication related to their transplant and HIV management.
  • For participant with a history of aspergillus colonization or disease, no evidence of active disease.
  • The participant must have, or be willing to start seeing, a primary medical care provider with expertise in HIV management.
  • All participants participating in sexual activity that could lead to pregnancy must use an FDA approved method of birth control.
  • 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.
  • 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 or may impact the quality or interpretation of the data obtained from the study.

Treatment and study plan

HIV D+/R+

Other

Kidney from an HIV-infected deceased donor

Primary outcomes

  1. Composite event, time to first death or graft failure or serious adverse event (SAE) or HIV breakthrough or opportunistic infection

    Time frame: From date of transplant through administrative censorship at study completion, up to 4 years

    Time to first of any of the following events: death or graft failure or serious adverse event (SAE) or HIV breakthrough or HIV virologic failure or opportunistic infection

Secondary outcomes

  1. 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 to mortality while enrolled before transplant (survival framework)

  2. Graft failure

    Time frame: From date of transplant through administrative censorship at study completion, up to 4 years

    Time to mortality or re-transplant or return to maintenance dialysis (survival framework)

  3. Rate of serious adverse events

    Time frame: From date of transplant through graft failure or administrative censorship at study completion, up to year 4

    Count of post-transplant serious adverse events per person-year as assessed by Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0

  4. 6-month acute rejection

    Time frame: From date of transplant to end of month 6

    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)

  5. 1-year acute 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 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)

  6. Incidence of graft rejection

    Time frame: From date of transplant through administrative censorship, up to 4 years

    Cumulative incidence of acute rejection (survival framework) 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)

  7. Graft function - Proportion eGFR <60 mL/min/1.73 m2

    Time frame: 3 months post-transplant

    Proportion of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2

  8. Graft function - Proportion eGFR <60 mL/min/1.73 m2

    Time frame: 6 months post-transplant

    Proportion of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2

  9. Graft function - Proportion eGFR <60 mL/min/1.73 m2

    Time frame: 9 months post-transplant

    Proportion of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2

  10. Graft function - Proportion eGFR <60 mL/min/1.73 m2

    Time frame: 1 year post-transplant

    Proportion of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2

  11. Graft function - Proportion eGFR <60 mL/min/1.73 m2

    Time frame: 2 years post-transplant

    Proportion of participants with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2

  12. Graft function - Proportion eGFR <60 mL/min/1.73 m2

    Time frame: 3 years post-transplant

    Proportion of participants with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2

  13. Graft function -mean eGFR

    Time frame: 3 months post-transplant

    Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

  14. Graft function-mean eGFR

    Time frame: 6 months post-transplant

    Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

  15. Graft function-mean eGFR

    Time frame: 9 months post-transplant

    Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

  16. Graft function-mean eGFR

    Time frame: 1 year post-transplant

    Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

  17. Graft function-mean eGFR

    Time frame: 2 years post-transplant

    Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

  18. Graft function-mean eGFR

    Time frame: 3 years post-transplant

    Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

  19. Graft function - slope eGFR

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

    The slope of glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) over time (longitudinal analysis)

  20. Incidence of non-HIV renal disease

    Time frame: 6 months post-transplant

    Cumulative incidence of non HIV-related renal disease as measured by biopsy, e.g. focal segmental glomerulosclerosis

  21. Incidence of non-HIV renal disease

    Time frame: 1 year post-transplant

    Cumulative incidence of non HIV-related renal disease as measured by biopsy, e.g. focal segmental glomerulosclerosis

  22. Incidence of HIV-related renal disease

    Time frame: 6 months post-transplant

    Cumulative incidence of non HIV-related renal disease as measured by biopsy, e.g. HIV-associated nephropathy

  23. Incidence of HIV-related renal disease

    Time frame: 1 year post-transplant

    Cumulative incidence of non HIV-related renal disease as measured by biopsy, e.g. HIV-associated nephropathy

  24. Donor and recipient apolipoprotein L1 (APOL1)

    Time frame: Baseline

    Proportion of transplant recipients with at least 1 apolipoprotein L1 (APOL1) risk variant in donor and recipient

  25. HIV infection of renal allografts

    Time frame: 6 months post-transplant

    Proportion of recipients with HIV seen in laser capture microdissection of renal biopsy

  26. 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 (longitudinal model)

  27. 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 Cluster of Differentiation 4 (CD4) count (longitudinal model)

  28. Incidence of antiretroviral resistance

    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

  29. Incidence of X4 tropic virus

    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

  30. Incidence of opportunistic infection

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

    Cumulative incidence of opportunistic infections

  31. Incidence 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

  32. Incidence of vascular complications

    Time frame: From date of transplant through year 1

    Number of vascular complications within 1 year of transplant

  33. Incidence 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

  34. Incidence 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

  35. Composite event, time to first

    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

Important dates

Study start
2018
Primary completion
2022
Study completion
2024
First posted
Apr 18, 2018
Registry last updated
Jul 23, 2024

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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