Clinical trial NCT03500315: HOPE in Action Prospective Multicenter, Clinical Trial of Deceased HIVD+ Kidney Transplants for HIV+ Recipients
Official title: HOPE in Action Prospective Multicenter, Clinical Trial of Deceased HIVD+ Kidney Transplants for HIV+ Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hiv
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2018-04-18
Enrollment: 209
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Composite event, time to first death or graft failure or serious adverse event (SAE) or HIV breakthrough or opportunistic infection
timeFrame: From date of transplant through administrative censorship at study completion, up to 4 years
Secondary outcomes:
measure: Pre-transplant mortality
timeFrame: From date of enrollment to date of transplant or death of any cause, whichever comes first, assessed up to 4 years
measure: Graft failure
timeFrame: From date of transplant through administrative censorship at study completion, up to 4 years
measure: Rate of serious adverse events
timeFrame: From date of transplant through graft failure or administrative censorship at study completion, up to year 4
measure: 6-month acute rejection
timeFrame: From date of transplant to end of month 6
measure: 1-year acute rejection
timeFrame: From date of transplant to end of year 1
measure: Incidence of graft rejection
timeFrame: From date of transplant through administrative censorship, up to 4 years
measure: Graft function - Proportion eGFR <60 mL/min/1.73 m2
timeFrame: 3 months post-transplant
measure: Graft function - Proportion eGFR <60 mL/min/1.73 m2
timeFrame: 6 months post-transplant
measure: Graft function - Proportion eGFR <60 mL/min/1.73 m2
timeFrame: 9 months post-transplant
measure: Graft function - Proportion eGFR <60 mL/min/1.73 m2
timeFrame: 1 year post-transplant
measure: Graft function - Proportion eGFR <60 mL/min/1.73 m2
timeFrame: 2 years post-transplant
measure: Graft function - Proportion eGFR <60 mL/min/1.73 m2
timeFrame: 3 years post-transplant
measure: Graft function -mean eGFR
timeFrame: 3 months post-transplant
measure: Graft function-mean eGFR
timeFrame: 6 months post-transplant
measure: Graft function-mean eGFR
timeFrame: 9 months post-transplant
measure: Graft function-mean eGFR
timeFrame: 1 year post-transplant
measure: Graft function-mean eGFR
timeFrame: 2 years post-transplant
measure: Graft function-mean eGFR
timeFrame: 3 years post-transplant
measure: Graft function - slope eGFR
timeFrame: From date of transplant to end of follow-up, up to 4 years
measure: Incidence of non-HIV renal disease
timeFrame: 6 months post-transplant
measure: Incidence of non-HIV renal disease
timeFrame: 1 year post-transplant
measure: Incidence of HIV-related renal disease
timeFrame: 6 months post-transplant
measure: Incidence of HIV-related renal disease
timeFrame: 1 year post-transplant
measure: Donor and recipient apolipoprotein L1 (APOL1)
timeFrame: Baseline
measure: HIV infection of renal allografts
timeFrame: 6 months post-transplant
measure: Trajectory of recipient plasma HIV RNA over time
timeFrame: From date of transplant through end of follow-up, up to 4 years
measure: Trajectory of recipient Cluster of Differentiation (CD4) count over time
timeFrame: From date of transplant through end of follow up, up to 4 years
measure: Incidence of antiretroviral resistance
timeFrame: From date of transplant through end of follow-up, up to 4 years
measure: Incidence of X4 tropic virus
timeFrame: From date of transplant through end of follow-up, up to 4 years
measure: Incidence of opportunistic infection
timeFrame: From date of transplant through end of follow-up, up to 4 years
measure: Incidence of surgical complications
timeFrame: From date of transplant through year 1
measure: Incidence of vascular complications
timeFrame: From date of transplant through year 1
measure: Incidence of viral-related malignancies
timeFrame: From date of transplant through end of follow-up, up to 4 years
measure: Incidence of the formation of de novo donor-specific human leukocyte antigen(HLA) antibodies
timeFrame: From date of transplant through end of year 1
measure: Composite event, time to first
timeFrame: From date of transplant through end of follow-up, up to 4 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: MedStar Georgetown Transplant Institute
state: District of Columbia
city: Miami
country: United States
facility: Miami Transplant Institute
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland, Institute of Human Virology
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: Drexel University
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC-University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Methodist Health System Clinical Research Institute
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Johns Hopkins University
name: Christine Durand, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.