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

Conditions

Hiv

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.

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.

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.

2026-03-13

10.1093/infdis/jiag154

Human antibody repertoire among kidney donors with and without HIV.

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 KM, Blumberg E, Elias N, Castillo-Lugo JA, Giorgakis E, Apewokin S, Grabowski MK, Segev DL, Redd AD, Durand CM, Larman HB, Tobian AA.

2026-03-12

10.1172/jci.insight.203645

Safety of Kidney Transplantation from Donors with HIV.

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.

2024-10-0128 citations

10.1056/nejmoa2403733

Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act

Jennifer D. Motter, Sarah Hussain, Diane Brown, Sander Florman, Meenakshi Rana et al. (35 authors)

Transplantation2023-11-2827 citations

10.1097/tp.0000000000004857

National Landscape of Human Immunodeficiency Virus–Positive Deceased Organ Donors in the United States

William A. Werbel, Diane Brown, Oyinkansola Kusemiju, Brianna Doby, Shanti Seaman et al. (100 authors)

Clinical Infectious Diseases2021-08-2821 citations

10.1093/cid/ciab743

Interventions

OTHERHIV D+/R+

Kidney from an HIV-infected deceased donor

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
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 HIV virologic failure or opportunistic infection

Secondary

Measure	Time frame	Description
Donor and Recipient Apolipoprotein L1 (APOL1)	Baseline	Percentage of transplant recipients with at least 1 apolipoprotein L1 (APOL1) risk variant in donor and recipient
Participants With Undetectable HIV RNA	From date of transplant through end of follow-up, up to 4 years	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.
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
Graft Function-mean eGFR	6 months post-transplant	Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Pre-transplant Mortality	At 1 and 2 years post-consent, prior to transplant	Cumulative incidence of mortality while enrolled before transplant
Graft Failure	At 1 and 3 years post transplant	Cumulative incidence of graft failure
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	At 6 months post-transplant	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).
1-year Acute Rejection	From date of transplant to end of year 1	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).
Incidence of Graft Rejection	At 1 and 3 years post transplant	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).
Graft Function - Number of Participants With eGFR <60 mL/Min/1.73 m^2	At 3 months post-transplant	Number of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) \< 60 mL/min/1.73 m2
Graft Function Number of Participants With eGRF<60 mL/Min/1.73 m^2	At year 2 post-transplant	Percentage of participants with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) \<60 mL/min/1.73 m\^2
Graft Function -Mean eGFR	3 months post-transplant	Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
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
Participants With Formation of de Novo Donor-specific Human Leukocyte Antigen(HLA) Antibodies	From date of transplant through end of year 1	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.
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)
Composite Event, Cumulative Incidence	At 6 months, 1 and 3 years post-transplant	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

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORChristine Durand, MD

Johns Hopkins University

Participant flow

Pre-assignment details

510 participants agreed to participate. Per protocol, particiants were not considered enrolled (n=207) until transplant. For the observational arm, only time to graft failure and acute rejection were collected, obtained from Scientific Registry of Transplant Recipients (September 2023 data export). Other outcome data were not collected on observational arm.

Baseline characteristics

Characteristic	—
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	2 Participants
Age, Categorical Between 18 and 65 years	173 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	89 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	6 Participants
Race (NIH/OMB) Black or African American	153 Participants
Race (NIH/OMB) More than one race	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants
Race (NIH/OMB) White	34 Participants
Region of Enrollment United States	99 Participants
Sex: Female, Male Female	16 Participants
Sex: Female, Male Male	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	12 / 99	11 / 99
other Total, other adverse events	11 / 99	4 / 99
serious Total, serious adverse events	74 / 99	76 / 99

Outcome results

None listed