Observational Study of Solid Organ Transplantation Utilizing HIV-Positive Donors in HIV-Positive Recipients

This is a prospective observational study of solid organ transplantation utilizing
HIV-positive donors in HIV-positive recipients. Stable HIV-infected adults in need of a solid
organ transplant (kidney, liver) who meet standard and study specified HIV criteria for organ
transplantation will be offered enrollment in the study. Deceased donors (kidney, liver) and
living donors (liver) will be utilized in this protocol. No living kidney donors will be
enrolled.

This study will evaluate overall survival and graft survival. In addition the study will
assess potential complications of organ transplant using HIV+ donor organs, including but not
limited to: HIV disease progression, development of antiretroviral resistance mutations,
incidence of opportunistic infections, incidence of transplant complications, impacts of
liver regeneration, incidence of viral-related malignancies, and incidence of
HIV-superinfection.

RECIPIENT ELIGIBILITY CRITERIA HIV-Positive Recipient Inclusion Criteria (liver, kidney)

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 IFA, or documented history of detectable HIV-1 RNA).

4. Participant is ≥ 18 years old.

5. No evidence of active opportunistic complications of HIV infection.

6. Participant CD4+ T-cell count is >/= 200/µL within 16 weeks prior to transplant for
kidney transplant recipients. For liver transplant recipient, CD4+ T-cell counts need
to be >/= 100/ul (or >/= 200/µL if history of opportunistic infection) within 16 weeks
prior to transplant.

7. Participant most recent HIV-1 RNA < 50 copies/mL (by any FDA-approved assay performed
in CLIA-approved laboratory), in the 26 weeks prior to transplant. Participants unable
to tolerate 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 once organ
function is restored after transplantation.

8. Concurrence by the study team that based on medical history and ART, viral suppression
can be achieved in the recipient post-transplant.

9. No history of primary CNS lymphoma or progressive PML.

10. On a stable antiretroviral regimen. Participants unable to tolerate ART due to organ
failure may still be considered eligible if the study team is confident there will be
a safe, tolerable, and effective antiretroviral regimen once organ function is
restored after transplantation.

HIV-Positive Recipient Exclusion Criteria (liver, kidney)

1. Participant has concomitant conditions that, in the judgment of the investigators, would
preclude transplantation or immunosuppression.

DONOR ELIGIBILITY CRITERIA HIV-Positive Deceased Donor (liver, kidney)

1. Must meet all clinical criteria for HIV-uninfected organ donors.

2. No evidence of invasive opportunistic complications of HIV infection.

3. Pre-implant donor organ biopsy showing no disease process that would put the recipient
at increased risk of rapid progression to end-stage organ failure, to be stored for
the duration of the study.

4. Donor has documented HIV infection (by any licensed ELISA and confirmation by Western
Blot, positive HIV ab IFA, or history of detectable HIV-1 RNA) from a CLIA-approved
laboratory.

5. If known history of HIV infection and prior antiretroviral therapy, the study team
must describe the anticipated post-transplant antiretroviral regimen to be prescribed
for the recipient and justify its conclusion that the regimen will be safe, tolerable
and effective.

HIV-Positive Living Donor (liver)

1. Donor meets all clinical criteria to be a living liver donor other than being HIV
positive.

2. Donor has documented HIV infection (by any licensed ELISA and confirmation by Western
Blot, positive HIV ab IFA, or history of detectable HIV-1 RNA) from a CLIA-approved
laboratory.

3. No evidence of invasive opportunistic complications of HIV infection

4. Donor CD4+ T-cell count is >/= 500/µL in the 26 weeks prior to donation.

5. The most recent HIV-1 RNA has been below 50 copies RNA/ml in the 26 weeks prior to
donation.

6. On a stable antiretroviral regimen.

7. Must be evaluated by the HIV/Transplant Infectious Diseases team to verify resistance
history and current ART regimens. The potential for transmission of resistant strain
of HIV will be assessed.

8. Pre-implant donor liver biopsy to be stored for the duration of the study showing no
evidence of a disease process that would put the donor at increased risk of
progressing to end-stage organ failure after donation, or that would present a risk of
poor graft function to the recipient.

9. Must be evaluated by an independent HIV study living donor advocate separate from the
transplant service in addition to the living donor advocate seen by all living donors.