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.

Study Overview

• Status: Completed
• Conditions: Hiv
• Intervention / Treatment: Other: HIV D+/R+

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 Type: Interventional
• Enrollment (Actual): 207
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • San Diego, California, United States, 92103
      • University of California, San Diego
    • San Francisco, California, United States, 94193
      • University of California, San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8022
      • Yale University School of Medicine
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • MedStar Georgetown Transplant Institute
  • Florida
    • Miami, Florida, United States, 33136
      • Miami Transplant Institute
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
    • Baltimore, Maryland, United States, 212101
      • University of Maryland, Institute of Human Virology
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical center
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10016
      • New York University School of Medicine
    • New York, New York, United States, 10029
      • Icahn School Of Medicine At Mount Sinai
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC-University of Pittsburgh Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75203
      • Methodist Health System Clinical Research Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
Experimental: HIV D+/R+; HIV-infected individuals that accept an organ from an HIV-infected deceased donor - enrollment 100	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 100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From date of transplant through administrative censorship at study completion, up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-transplant Mortality	Cumulative incidence of mortality while enrolled before transplant	At 1 and 2 years post-consent, prior to transplant
Graft Failure	Cumulative incidence of graft failure	At 1 and 3 years post transplant
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	From date of transplant through graft failure or administrative censorship at study completion, up to year 4
6-month Acute Rejection	Percentage 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). Outcome data of the observational group were obtained from the Scientific Registry of Transplant Recipients (September 2023 data export).	At 6 months post-transplant
1-year Acute Rejection	Percentage 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). Outcome data of the observational group were obtained from the Scientific Registry of Transplant Recipients (September 2023 data export).	From date of transplant to end of year 1
Incidence of Graft Rejection	Cumulative incidence of 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). Outcome data of the observational group were obtained from the Scientific Registry of Transplant Recipients (September 2023 data export).	At 1 and 3 years post transplant
Graft Function - Number of Participants With eGFR <60 mL/Min/1.73 m^2	Number of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2	At 3 months post-transplant
Graft Function - Number of Participants With eGFR <60 mL/Min/1.73 m^2	Number of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) <60 mL/min/1.73 m^2	At 6 months post-transplant
Graft Function - Number of Participants With eGFR <60 mL/Min/1.73 m^2	Number of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) <60 mL/min/1.73 m^2	9 months post-transplant
Graft Function - Number of Participants With eGFR <60 mL/Min/1.73 m^2	Number of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) <60 mL/min/1.73 m^2	At year 1 post-transplant
Graft Function Number of Participants With eGRF<60 mL/Min/1.73 m^2	Percentage of participants with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) <60 mL/min/1.73 m^2	At year 2 post-transplant
Graft Function - Number of Participants With eGFR <60 mL/Min/1.73 m^2	Percentage of participants with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) <60 mL/min/1.73 m^2	At year 3 post-transplant
Graft Function -Mean eGFR	Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)	3 months post-transplant
Graft Function-mean eGFR	Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)	6 months post-transplant
Graft Function-mean eGFR	Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)	9 months post-transplant
Graft Function-mean eGFR	Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)	1 year post-transplant
Graft Function-mean eGFR	Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)	2 years post-transplant
Graft Function-mean eGFR	Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)	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)	From date of transplant to end of follow-up, up to 4 years
Donor and Recipient Apolipoprotein L1 (APOL1)	Percentage of transplant recipients with at least 1 apolipoprotein L1 (APOL1) risk variant in donor and recipient	Baseline
Participants With Undetectable HIV RNA	Trajectory of recipient plasma HIV RNA over time. Analysis of repeated measures of plasma HIV RNA (longitudinal model). Below 50 copies/mL was used as the threshold of undetectable HIV RNA.	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)	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	From date of transplant through end of follow-up, up to 4 years
Incidence of X4 Tropic Virus	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	From date of transplant through end of follow-up, up to 4 years
Incidence of Opportunistic Infection	Cumulative incidence of opportunistic infections	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	From date of transplant through year 1
Incidence of Vascular Complications	Number of vascular complications within 1 year of transplant	From date of transplant through year 1
Incidence of Viral-related Malignancies	Number of malignancies as determined by local pathology	From date of transplant through end of follow-up, up to 4 years
Participants With Formation of de Novo Donor-specific Human Leukocyte Antigen(HLA) Antibodies	Participants must have donor-specific HLA data at both day 0 and at 1 year to be included in the analysis. A total of 32 HIV D+/R+ and 40 HIV D-/R+ participants were excluded due to missing donor-specific data at either day 0 or 1 year.	From date of transplant through end of year 1
Composite Event, Cumulative Incidence	Cumulative incidence of the composite event, which is defined as the occurrence of first event of any of all-cause-mortality or graft failure or renal allograft rejection or HIV breakthrough or HIV virologic failure or AIDS defining illness	At 6 months, 1 and 3 years post-transplant

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Christine Durand, MD, Johns Hopkins University

Publications and helpful links

General Publications

• Werbel WA, Brown DM, Kusemiju OT, Doby BL, Seaman SM, Redd AD, Eby Y, Fernandez RE, Desai NM, Miller J, Bismut GA, Kirby CS, Schmidt HA, Clarke WA, Seisa M, Petropoulos CJ, Quinn TC, Florman SS, Huprikar S, Rana MM, Friedman-Moraco RJ, Mehta AK, Stock PG, Price JC, Stosor V, Mehta SG, Gilbert AJ, Elias N, Morris MI, Mehta SA, Small CB, Haidar G, Malinis M, Husson JS, Pereira MR, Gupta G, Hand J, Kirchner VA, Agarwal A, Aslam S, Blumberg EA, Wolfe CR, Myer K, Wood RP, Neidlinger N, Strell S, Shuck M, Wilkins H, Wadsworth M, Motter JD, Odim J, Segev DL, Durand CM, Tobian AAR; HOPE in Action Investigators. National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States. Clin Infect Dis. 2022 Jun 10;74(11):2010-2019. doi: 10.1093/cid/ciab743.
• Sulaiman A, Tamil Selvan M, Yang P, Zhu X, Eby Y, Benner SE, Fernandez RE, Hussain S, Brown D, Desai N, Florman S, Rana MM, Friedman-Moraco R, Pereira MR, Mehta S, Stock P, Gilbert A, Morris MI, Stosor V, Mehta SA, Small CB, Ranganna K, Santos CAQ, Aslam S, Malinis M, Elias N, Blumberg EA, Massie A, Smith ML, Morsheimer M, Laird GM, Siliciano R, Segev DL, Durand CM, Redd AD, Tobian AA. Allograft Rejection and the Latent HIV Reservoir in Kidney Transplant Recipients with HIV. J Infect Dis. 2026 Mar 13:jiag154. doi: 10.1093/infdis/jiag154. Online ahead of print.
• Zhu X, Morgenlander WR, Brown DM, Eby Y, Morsheimer M, Odim J, Bagnasco SM, Rana MM, Florman SS, Friedman-Moraco RJ, Stock PG, Gilbert AJ, Mehta S, Stosor V, Mehta SA, Pereira MR, Small CB, Morris MI, Hand J, Aslam S, Haidar G, Malinis M, Santos CA, Schaenman J, Wojciechowski D, Ranganna K, Blumberg E, Elias N, Castillo-Lugo JA, Giorgakis E, Apewokin S, Grabowski MK, Segev DL, Redd AD, Durand CM, Larman HB, Tobian AA; HOPE in Action investigators. Human antibody repertoire among kidney donors with and without HIV. JCI Insight. 2026 Mar 12;11(8):e203645. doi: 10.1172/jci.insight.203645. eCollection 2026 Apr 22.
• Freercks R, Rodrigues M, Manning K, Heymann J, Kopp JB, Nagiah S, Rana M, Florman S, Friedman-Moraco R, Stock P, Gilbert A, Mehta S, Stosor V, Pereira MR, Morris MI, Hand J, Haidar G, Malinis M, Santos CAQ, Schaenman J, Blumberg EA, Wojciechowski D, Odim J, Massie A, Selvan MT, Bagnasco S, Segev D, Tobian AAR, Muller E, Durand CM, Redd AD. APOL1 Genotype and Patient Outcomes in US and South African Transplant Recipients With HIV who Received Kidneys From Donors With HIV. Transplantation. 2026 Apr 1;110(4):e897-e904. doi: 10.1097/TP.0000000000005556. Epub 2025 Nov 17.
• Durand CM, Massie A, Florman S, Liang T, Rana MM, Friedman-Moraco R, Gilbert A, Stock P, Mehta SA, Mehta S, Stosor V, Pereira MR, Morris MI, Hand J, Aslam S, Malinis M, Haidar G, Small CB, Santos CAQ, Schaenman J, Baddley J, Wojciechowski D, Blumberg EA, Ranganna K, Adebiyi O, Elias N, Castillo-Lugo JA, Giorgakis E, Apewokin S, Brown D, Ostrander D, Eby Y, Desai N, Naqvi F, Bagnasco S, Watson N, Brittain E, Odim J, Redd AD, Tobian AAR, Segev DL; HOPE in Action Investigators. Safety of Kidney Transplantation from Donors with HIV. N Engl J Med. 2024 Oct 17;391(15):1390-1401. doi: 10.1056/NEJMoa2403733.

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2018
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): May 1, 2024

Study Registration Dates

• First Submitted: April 2, 2018
• First Submitted That Met QC Criteria: April 12, 2018
• First Posted (Actual): April 18, 2018

Study Record Updates

• Last Update Posted (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: IRB00141138; U01AI134591 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No