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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HIV Infection

Intervention / Treatment
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* Other: HIV-infected deceased donor organ


Participation Criteria
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Eligibility Criteria
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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. Participant is able to understand and provide informed consent Participant meets standard listing criteria for transplant. 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). Participant is > 18 years old. 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. Participant CD4+ T-cell count is >/= 200/µL in the 16 weeks prior to transplant. 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. Participant is willing to use Pneumocystis Carinii Pneumonia (PCP), herpes virus and fungal prophylaxis as indicated. Exclusion Criteria: Participant has concomitant conditions that, in the judgment of the investigators, would preclude transplantation or immunosuppression. Opportunistic Complication History: Any history of progressive multifocal leukoencephalopathy (PML), chronic intestinal cryptosporidiosis of > 1 month duration, or primary Central Nervous System (CNS) lymphoma. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV D+/R+<br>HIV-infected individuals who accept an organ from an HIV-infected deceased donor | Other: HIV-infected deceased donor organ<br>* HIV-infected deceased donor organ transplant<br>|
| HIV D-/R+<br>HIV-infected individuals who accept an organ from an HIV-uninfected deceased donor | |

What is the study measuring?
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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 |