Observational Study of HIV+ Deceased Donor Transplant for HIV+ Recipients

Observational Study of HIV+ Deceased Donor Solid Organ Transplant for HIV+ Recipients

HIV-infected (HIV+) individuals who agree to accept and receive a solid organ transplant from an HIV+ deceased donor will be followed to determine the safety and efficacy of this practice. Some HIV+ individuals who receive a solid organ transplant from HIV-uninfected (HIV-) donors will also be followed.

Study Overview

• Status: Recruiting
• Conditions: HIV Infection
• Intervention / Treatment: Other: HIV-infected deceased donor organ

Detailed Description

This is an observational study designed to evaluate safety and outcomes of solid organ transplantation in HIV+ recipients of HIV+ deceased donor organs. This study will evaluate overall survival and graft survival compared to transplantation with an HIV- organ.

In addition the study will assess potential complications of organ transplant using HIV+ deceased donors - including but not limited to - HIV superinfection, incidence and severity of graft rejection, recurrence of HIV-associated nephropathy, incidence of bacterial infections, and opportunistic infections.

• Study Type: Observational
• Enrollment (Estimated): 125

Contacts and Locations

• Study Contact: Name: Christine Durand, MD; Phone Number: 410-955-5684; Email: cdurand2@jhmi.edu
• Study Contact Backup: Name: Dorry Segev, MD, PhD; Email: dorry.segev@nyulangone.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Denver
      • Contact: Heidi Monroe, MS, RN; Phone Number: 720-848-2222; Email: heidi.monroe@uchealth.org
      • Contact: Esther Benamu, MD; Phone Number: 303-724-8769; Email: esther.benamu@ucdenver.edu
      • Principal Investigator: Esther Benamu, MD
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Completed
      • Yale University School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Recruiting
      • Georgetown University Medical Center
      • Contact: Alexander Gilbert, MD; Phone Number: 202-444-3700; Email: alexander.j.gilbert@gunet.georgetown.edu
      • Principal Investigator: Alexander Gilbert, MD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Contact: Nicole Turgeon, MD; Phone Number: 404-727-3257; Email: nturgeo@emory.edu
      • Principal Investigator: Nicole Turgeon, MD
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Principal Investigator: Valentina Stosor, MD
      • Contact: Valentina Stosor, MD; Phone Number: 312-695-5085; Email: v-stosor@northwestern.edu
    • Chicago, Illinois, United States, 60612
      • Completed
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60612
      • Completed
      • University of Illinois at Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University
      • Contact: Oluwafisayo Adebiyi, MD; Phone Number: 317-944-4370; Email: olabiy@iu.edu
      • Contact: Jeanne Chen, BS, PharmD; Phone Number: 317-944-3570; Email: jchen@iuhealth.org
      • Principal Investigator: Oluwafisayo Adebiyi, MD
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Johns Hopkins University
      • Contact: Christine Durand, MD; Phone Number: 410-955-5684; Email: cdurand2@jhmi.edu
      • Principal Investigator: Christine Durand, MD
      • Contact: Diane Brown, RN, MSN; Phone Number: 410-614-0648; Email: dbrown22@jhmi.edu
      • Principal Investigator: Dorry Segev, MD, PhD
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland, Institute of Human Virology
      • Principal Investigator: Jennifer Husson, MD
      • Contact: Jennifer Husson, MD; Phone Number: 410-706-8614; Email: jhusson@ihv.umaryland.edu
      • Contact: Ilise Marrazzo, RN; Phone Number: 410-706-2564; Email: imarrazzo@ihv.umaryland.edu
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Completed
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Contact: Sander Florman, MD; Phone Number: 212-659-8313; Email: sander.florman@mountsinai.org
      • Contact: Brandy Haydel; Phone Number: 212-241-0255; Email: brandy.haydel@mountsinai.org
      • Principal Investigator: Sander Florman, MD
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Contact: Cristina M. Falo, PhD; Phone Number: 212-305-3839; Email: cf2427@cumc.columbia.edu
      • Contact: Marcus Pereira, MD; Email: mp2323@cumc.columbia.edu
      • Principal Investigator: Marcus Pereira, MD
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medical College
      • Contact: Thangamani Muthukumar, MD; Phone Number: 212-746-4430; Email: mut9002@med.cornell.edu
      • Contact: Catherine Small, MD; Phone Number: 646-962-4800; Email: cbs9003@med.cornell.edu
      • Principal Investigator: Thangamani Muthukumar, MD
    • New York, New York, United States, 10016
      • Recruiting
      • New York University School of Medicine
      • Contact: Sapna Mehta, MD; Phone Number: 646-754-1006; Email: sapna.mehta@nyumc.org
      • Principal Investigator: Sapna Mehta, MD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Completed
      • University of Pittsburgh Medical Center
  • Texas
    • Dallas, Texas, United States, 75203
      • Recruiting
      • Methodist Health System
      • Contact: Jose A. Castillo-Lugo, MD; Phone Number: 214-358-2300; Email: castilloj@dneph.com
      • Principal Investigator: Jose A. Castillo-Lugo, MD
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia
      • Contact: Avinash Agarwal, MD; Phone Number: 434-924-9370; Email: AA4VB@hscmail.mcc.virginia.edu
      • Principal Investigator: Avinash Agarwal, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All individuals with end-stage organ disease and HIV infection who meet standard clinical criteria for transplantation and the study inclusion and exclusion criteria will be eligible for participation in the study.

Description

Inclusion Criteria:

All individuals with end-stage organ disease and HIV infection who meet standard clinical criteria for transplantation and the study inclusion and exclusion criteria will be eligible for participation in the study.

1. Participant is able to understand and provide informed consent
2. Participant meets standard listing criteria for transplant.
3. Documented HIV infection (by any licensed ELISA and confirmation by Western Blot, positive HIV Ab Immunofluorescence Assay (IFA), or documented history of detectable HIV-1 RNA).
4. Participant is > 18 years old.
5. Opportunistic Complications: None or previous history of protocol allowed opportunistic infections or neoplasms with appropriate acute and maintenance therapy and no evidence of active disease.
6. Participant CD4+ T-cell count is >/= 200/µL in the 16 weeks prior to transplant.
7. Participant most recent HIV-1 RNA < 50 copies/mL (by any FDA-approved assay performed in Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory) and on a stable antiretroviral regimen. Non-consecutive viral "blips" between 50-400 copies RNA/mL will be allowed. The Federal Register HIV Organ Policy Equity (HOPE) Act Final Safeguards and Research criteria does not specify a required frequency of HIV-1 RNA monitoring to determine recipient eligibility. The most recent HIV Viral Load (VL) should be < 50 copies, but this result can be documented outside the 16 week window according to the judgement of the local clinical team and site investigator. Organ recipients who are unable to tolerate Antiretroviral Therapy (ART) due to organ failure or who have only recently started ART may have detectable viral load and still be considered eligible if the study team is confident there will be a safe, tolerable, and effective antiretroviral regimen to be used by the recipient once organ function is restored after transplantation.
8. Participant is willing to use Pneumocystis Carinii Pneumonia (PCP), herpes virus and fungal prophylaxis as indicated.

Exclusion Criteria:

1. Participant has concomitant conditions that, in the judgment of the investigators, would preclude transplantation or immunosuppression.
2. Opportunistic Complication History: Any history of progressive multifocal leukoencephalopathy (PML), chronic intestinal cryptosporidiosis of > 1 month duration, or primary Central Nervous System (CNS) lymphoma.
3. Participant has a history of any neoplasm except for the following: resolved Kaposi's sarcoma, in situ anogenital carcinoma, adequately treated basal or squamous cell carcinoma of the skin, solid tumors (except primary CNS lymphoma) treated with curative therapy and disease free for more than 5 years. History of renal cell carcinoma requires disease free state for 2 years. History of leukemia and disease-free duration will be per site policy.
4. Participant is pregnant or breastfeeding. Note: Participants who become pregnant post-transplant will continue to be followed in the study and will be managed per clinical practice. Women that become pregnant should not breastfeed.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HIV D+/R+; HIV-infected individuals who accept an organ from an HIV-infected deceased donor	Other: HIV-infected deceased donor organ; HIV-infected deceased donor organ transplant
HIV D-/R+; HIV-infected individuals who accept an organ from an HIV-uninfected deceased donor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Patient survival at one year	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft survival	Transplanted organ function	one year, two years, 3 years, 4 years
Graft rejection	Incidence and severity of organ rejection	One year
HIV disease progression	Incidence of virologic breakthrough or failure	through study completion, up to 4 years
Antiretroviral resistance and X4 tropic virus	incidence of new antiretroviral drug resistance and/or X4 tropic virus	through study completion, up to 4 years
Incidence of bacterial, fungal, viral, and other opportunistic infection	incidence of bacterial, fungal, viral, and other opportunistic infections	through study completion, up to 4 years
Surgical complications	incidence of surgical and vascular transplant complications	within the first 3 months
Recurrent HIV-associated nephropathy	incidence of recurrent HIV-associated nephropathy in kidney recipients	through study completion, up to 4 years
Incidence of post-transplant Malignancy	incidence of post-transplant malignancies	through study completion, up to 4 years
Incidence of HIV superinfection in blood and/or tissue	Incidence of HIV superinfection in blood and/or tissue	measured at 3 months, 6 months, year 1, year 2, year 3, year 4
HIV latent reservoir	Frequency of infected CD4 T cells in blood	measured at 3 months, 6 months, year 1, year 2, year 3, year 4
Immune activation	Cytokine levels	measured at 3 months, 6 months, year 1, year 2, year 3, year 4

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: University of Colorado, Denver; National Institute of Allergy and Infectious Diseases (NIAID); Washington University School of Medicine; Northwestern University; Yale University; University of Maryland; Georgetown University; Columbia University; Icahn School of Medicine at Mount Sinai; NYU Langone Health; University of Illinois at Chicago; Emory University; Rush University Medical Center; Weill Medical College of Cornell University; University of Virginia; Indiana University; Methodist Health System; University of Pittsburgh Medical Center
• 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.
• Bonny TS, Kirby C, Martens C, Rose R, Desai N, Seisa M, Petropoulos C, Florman S, Friedman-Moraco RJ, Turgeon NA, Brown D, Segev DL, Durand CM, Tobian AAR, Redd AD. Outcomes of donor-derived superinfection screening in HIV-positive to HIV-positive kidney and liver transplantation: a multicentre, prospective, observational study. Lancet HIV. 2020 Sep;7(9):e611-e619. doi: 10.1016/S2352-3018(20)30200-9. Epub 2020 Jul 27.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: November 6, 2015
• First Submitted That Met QC Criteria: November 9, 2015
• First Posted (Estimated): November 11, 2015

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections
• Other Study ID Numbers: IRB00085148; JHUHIVDD (Other Identifier: Site Specific Identifier); 1U01AI134591-01 (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