Clinical trial NCT02602262: Observational Study of HIV+ Deceased Donor Transplant for HIV+ Recipients
Official title: Observational Study of HIV+ Deceased Donor Solid Organ Transplant for HIV+ Recipients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: HIV Infection
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: University of Colorado, Denver
name: Yale University
name: Georgetown University
name: Emory University
name: Rush University Medical Center
name: University of Illinois at Chicago
name: Indiana University
name: University of Maryland
name: Columbia University
name: Icahn School of Medicine at Mount Sinai
name: Weill Medical College of Cornell University
name: University of Pittsburgh Medical Center
name: Methodist Health System
name: Northwestern University
name: NYU Langone Health
name: University of Virginia
name: Washington University School of Medicine
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2015-11-11
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Survival
timeFrame: One year
Secondary outcomes:
measure: Graft survival
timeFrame: one year, two years, 3 years, 4 years
measure: Graft rejection
timeFrame: One year
measure: HIV disease progression
timeFrame: through study completion, up to 4 years
measure: Antiretroviral resistance and X4 tropic virus
timeFrame: through study completion, up to 4 years
measure: Incidence of bacterial, fungal, viral, and other opportunistic infection
timeFrame: through study completion, up to 4 years
measure: Surgical complications
timeFrame: within the first 3 months
measure: Recurrent HIV-associated nephropathy
timeFrame: through study completion, up to 4 years
measure: Incidence of post-transplant Malignancy
timeFrame: through study completion, up to 4 years
measure: Incidence of HIV superinfection in blood and/or tissue
timeFrame: measured at 3 months, 6 months, year 1, year 2, year 3, year 4
measure: HIV latent reservoir
timeFrame: measured at 3 months, 6 months, year 1, year 2, year 3, year 4
measure: Immune activation
timeFrame: measured at 3 months, 6 months, year 1, year 2, year 3, year 4
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
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: Baltimore
country: United States
facility: University of Maryland, Institute of Human Virology
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
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: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Methodist Health System
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.
citation: 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.