HOPE in Action Prospective Multicenter, Clinical Trial of Deceased HIVD+ Kidney Transplants for HIV+ Recipients
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HIV D+/R+ HIV-infected individuals that accept an organ from an HIV-infected deceased donor - enrollment 80 |
Other: HIV D+/R+
Kidney from an HIV-infected deceased donor
|
| No Intervention: HIV D-/R+ HIV-infected individuals that accept an organ from an HIV-uninfected deceased donor -enrollment 80 |
|
| No Intervention: HIV D-/R+ (observational) HIV-infected individuals that accept an organ from an HIV-uninfected deceased donor and randomized to observational group - enrollment 200 |
Outcome Measures
Primary Outcome Measures
- Composite event, time to first death or graft failure or serious adverse event (SAE) or HIV breakthrough or opportunistic infection [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 opportunistic infection
Secondary Outcome Measures
- 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 to mortality while enrolled before transplant (survival framework)
- Graft failure [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)
- Rate of serious adverse events [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
- 6-month acute rejection [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)
- 1-year acute rejection [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)
- Incidence of graft rejection [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)
- Graft function - Proportion eGFR <60 mL/min/1.73 m2 [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
- Graft function - Proportion eGFR <60 mL/min/1.73 m2 [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
- Graft function - Proportion eGFR <60 mL/min/1.73 m2 [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
- Graft function - Proportion eGFR <60 mL/min/1.73 m2 [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
- Graft function - Proportion eGFR <60 mL/min/1.73 m2 [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
- Graft function - Proportion eGFR <60 mL/min/1.73 m2 [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
- Graft function -mean eGFR [3 months post-transplant]
Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
- Graft function-mean eGFR [6 months post-transplant]
Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
- Graft function-mean eGFR [9 months post-transplant]
Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
- Graft function-mean eGFR [1 year post-transplant]
Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
- Graft function-mean eGFR [2 years post-transplant]
Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
- Graft function-mean eGFR [3 years post-transplant]
Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
- Graft function - slope eGFR [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)
- Incidence of non-HIV renal disease [6 months post-transplant]
Cumulative incidence of non HIV-related renal disease as measured by biopsy, e.g. focal segmental glomerulosclerosis
- Incidence of non-HIV renal disease [1 year post-transplant]
Cumulative incidence of non HIV-related renal disease as measured by biopsy, e.g. focal segmental glomerulosclerosis
- Incidence of HIV-related renal disease [6 months post-transplant]
Cumulative incidence of non HIV-related renal disease as measured by biopsy, e.g. HIV-associated nephropathy
- Incidence of HIV-related renal disease [1 year post-transplant]
Cumulative incidence of non HIV-related renal disease as measured by biopsy, e.g. HIV-associated nephropathy
- Donor and recipient apolipoprotein L1 (APOL1) [Baseline]
Proportion of transplant recipients with at least 1 apolipoprotein L1 (APOL1) risk variant in donor and recipient
- HIV infection of renal allografts [6 months post-transplant]
Proportion of recipients with HIV seen in laser capture microdissection of renal biopsy
- 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 (longitudinal model)
- 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 Cluster of Differentiation 4 (CD4) count (longitudinal model)
- Incidence of antiretroviral resistance [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
- Incidence of X4 tropic virus [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
- Incidence of opportunistic infection [From date of transplant through end of follow-up, up to 4 years]
Cumulative incidence of opportunistic infections
- Incidence 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
- Incidence of vascular complications [From date of transplant through year 1]
Number of vascular complications within 1 year of transplant
- Incidence 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
- Incidence 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
- Composite event, time to first [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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participant meets the standard criteria for kidney transplant at the local center.
-
Participant is able to understand and provide informed consent.
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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).
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No living donor available.
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Participant is ≥18 years old.
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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.
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The participant must have, or be willing to start seeing, a primary medical care provider with expertise in HIV management.
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All participants participating in sexual activity that could lead to pregnancy must use an FDA approved method of birth control.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35294 |
| 2 | University of Arkansas for Medical Sciences | Little Rock | Arkansas | United States | 72205 |
| 3 | University of California, Los Angeles | Los Angeles | California | United States | 90095 |
| 4 | University of California, San Diego | San Diego | California | United States | 92103 |
| 5 | University of California, San Francisco | San Francisco | California | United States | 94193 |
| 6 | Yale University School of Medicine | New Haven | Connecticut | United States | 06520-8022 |
| 7 | MedStar Georgetown Transplant Institute | Washington | District of Columbia | United States | 20007 |
| 8 | Miami Transplant Institute | Miami | Florida | United States | 33136 |
| 9 | Cleveland Clinic Florida | Weston | Florida | United States | 33331 |
| 10 | Emory University | Atlanta | Georgia | United States | 30322 |
| 11 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 12 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 13 | University of Illinois at Chicago | Chicago | Illinois | United States | 60612 |
| 14 | Indiana University | Indianapolis | Indiana | United States | 46202 |
| 15 | Ochsner Medical Center | New Orleans | Louisiana | United States | 70121 |
| 16 | Johns Hopkins University | Baltimore | Maryland | United States | 21205 |
| 17 | University of Maryland, Institute of Human Virology | Baltimore | Maryland | United States | 212101 |
| 18 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 19 | New York University School of Medicine | New York | New York | United States | 10016 |
| 20 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
| 21 | Columbia University Medical Center | New York | New York | United States | 10032 |
| 22 | Weill Cornell Medical College | New York | New York | United States | 10065 |
| 23 | University of Cincinnati | Cincinnati | Ohio | United States | 45267 |
| 24 | Drexel University | Philadelphia | Pennsylvania | United States | 19102 |
| 25 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 26 | UPMC-University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States | 15213 |
| 27 | Methodist Health System Clinical Research Institute | Dallas | Texas | United States | 75203 |
| 28 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
| 29 | University of Virginia | Charlottesville | Virginia | United States | 22908 |
Sponsors and Collaborators
- Johns Hopkins University
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Principal Investigator: Christine Durand, MD, Johns Hopkins University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB00141138
- U01AI134591