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

Johns Hopkins University209 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

209

Conditions

Hiv

Interventions

HIV D+/R+OTHER

Kidney from an HIV-infected deceased donor

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (29)

Outcomes

Primary Outcomes

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

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

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

Secondary Outcomes

Pre-transplant mortality

Time to mortality while enrolled before transplant (survival framework)

Time frame: From date of enrollment to date of transplant or death of any cause, whichever comes first, assessed up to 4 years

Graft failure

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

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

Rate of serious adverse events

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

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

6-month acute rejection

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)

Data from ClinicalTrials.gov

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University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

University of California, Los Angeles

Los Angeles, California, 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

MedStar Georgetown Transplant Institute

Washington D.C., District of Columbia, United States

Miami Transplant Institute

Miami, Florida, United States

Cleveland Clinic Florida

Weston, Florida, United States

Emory University

Atlanta, Georgia, United States

...and 19 more locations

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

1-year acute rejection

Time frame: From date of transplant to end of year 1

Incidence of graft rejection

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)

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

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

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

Time frame: 3 months post-transplant

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

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

Time frame: 6 months post-transplant

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

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

Time frame: 9 months post-transplant

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

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

Time frame: 1 year post-transplant

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

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

Time frame: 2 years post-transplant

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

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

Time frame: 3 years post-transplant

Graft function -mean eGFR

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

Time frame: 3 months post-transplant

Graft function-mean eGFR

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

Time frame: 6 months post-transplant

Graft function-mean eGFR

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

Time frame: 9 months post-transplant

Graft function-mean eGFR

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

Time frame: 1 year post-transplant

Graft function-mean eGFR

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

Time frame: 2 years post-transplant

Graft function-mean eGFR

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

Time frame: 3 years post-transplant

Graft function - slope eGFR

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

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

Incidence of non-HIV renal disease

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

Time frame: 6 months post-transplant

Incidence of non-HIV renal disease

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

Time frame: 1 year post-transplant

Incidence of HIV-related renal disease

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

Time frame: 6 months post-transplant

Incidence of HIV-related renal disease

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

Time frame: 1 year post-transplant

Donor and recipient apolipoprotein L1 (APOL1)

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

Time frame: Baseline

HIV infection of renal allografts

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

Time frame: 6 months post-transplant

Trajectory of recipient plasma HIV RNA over time

Analysis of repeated measures of plasma HIV RNA (longitudinal model)

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

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

Analysis of repeated measures of Cluster of Differentiation 4 (CD4) count (longitudinal model)

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

Incidence of antiretroviral resistance

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

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

Incidence of X4 tropic virus

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

Incidence of opportunistic infection

Cumulative incidence of opportunistic infections

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

Incidence of surgical complications

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

Time frame: From date of transplant through year 1

Incidence of vascular complications

Number of vascular complications within 1 year of transplant

Time frame: From date of transplant through year 1

Incidence of viral-related malignancies

Number of malignancies as determined by local pathology

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

Incidence of the formation of de novo donor-specific human leukocyte antigen(HLA) antibodies

Proportion of participants with a de novo donor-specific HLA antibody as measured and reported by local sites' lab

Time frame: From date of transplant through end of year 1

Composite event, time to first

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

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