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

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT02602262
• Collaborator: University of Colorado, Denver (Other), Yale University (Other), Georgetown University (Other), Emory University (Other), Rush University Medical Center (Other), University of Illinois at Chicago (Other), Indiana University (Other), University of Maryland, Institute of Human Virology (Other), Columbia University (Other), Icahn School of Medicine at Mount Sinai (Other), Weill Medical College of Cornell University (Other), University of Pittsburgh Medical Center (Other), Methodist Health System (Other), Northwestern University (Other), NYU Langone Health (Other), University of Virginia (Other), Washington University School of Medicine (Other), National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 125
• Locations: 18
• Duration (Months): 103
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infection	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 Design

• Study Type: Observational
• Anticipated Enrollment: 125 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Observational Study of HIV+ Deceased Donor Solid Organ Transplant for HIV+ Recipients
• Study Start Date: Nov 1, 2015
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Jun 1, 2024

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

1. Survival [One year]

   Patient survival at one year

Secondary Outcome Measures

1. Graft survival [one year, two years, 3 years, 4 years]

   Transplanted organ function

2. Graft rejection [One year]

   Incidence and severity of organ rejection

3. HIV disease progression [through study completion, up to 4 years]

   Incidence of virologic breakthrough or failure

4. Antiretroviral resistance and X4 tropic virus [through study completion, up to 4 years]

   incidence of new antiretroviral drug resistance and/or X4 tropic virus

5. Incidence of bacterial, fungal, viral, and other opportunistic infection [through study completion, up to 4 years]

   incidence of bacterial, fungal, viral, and other opportunistic infections

6. Surgical complications [within the first 3 months]

   incidence of surgical and vascular transplant complications

7. Recurrent HIV-associated nephropathy [through study completion, up to 4 years]

   incidence of recurrent HIV-associated nephropathy in kidney recipients

8. Incidence of post-transplant Malignancy [through study completion, up to 4 years]

   incidence of post-transplant malignancies

9. Incidence of HIV superinfection in blood and/or tissue [measured at 3 months, 6 months, year 1, year 2, year 3, year 4]

   Incidence of HIV superinfection in blood and/or tissue

10. HIV latent reservoir [measured at 3 months, 6 months, year 1, year 2, year 3, year 4]

    Frequency of infected CD4 T cells in blood

11. Immune activation [measured at 3 months, 6 months, year 1, year 2, year 3, year 4]

    Cytokine levels

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Denver	Aurora	Colorado	United States	80045
2	Yale University School of Medicine	New Haven	Connecticut	United States	06520
3	Georgetown University Medical Center	Washington	District of Columbia	United States	20057
4	Emory University	Atlanta	Georgia	United States	30322
5	Northwestern University	Chicago	Illinois	United States	60611
6	Rush University Medical Center	Chicago	Illinois	United States	60612
7	University of Illinois at Chicago	Chicago	Illinois	United States	60612
8	Indiana University	Indianapolis	Indiana	United States	46202
9	University of Maryland, Institute of Human Virology	Baltimore	Maryland	United States	21201
10	Johns Hopkins University	Baltimore	Maryland	United States	21205
11	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
12	New York University School of Medicine	New York	New York	United States	10016
13	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
14	Columbia University Medical Center	New York	New York	United States	10032
15	Weill Cornell Medical College	New York	New York	United States	10065
16	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
17	Methodist Health System	Dallas	Texas	United States	75203
18	University of Virginia	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

• Johns Hopkins University
• University of Colorado, Denver
• Yale University
• Georgetown University
• Emory University
• Rush University Medical Center
• University of Illinois at Chicago
• Indiana University
• University of Maryland, Institute of Human Virology
• Columbia University
• Icahn School of Medicine at Mount Sinai
• Weill Medical College of Cornell University
• University of Pittsburgh Medical Center
• Methodist Health System
• Northwestern University
• NYU Langone Health
• University of Virginia
• Washington University School of Medicine
• 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.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT02602262
• Other Study ID Numbers: IRB00085148; JHUHIVDD; 1U01AI134591-01
• First Posted: Nov 11, 2015
• Last Update Posted: May 5, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: HIV Infections

Study Results

No Results Posted as of May 5, 2022