Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients

MVC is a CCR5 inhibitor that may have a positive role in modulating the immune response
following transplantation. The purpose of this study is to evaluate the safety and
tolerability of MVC in HIV-infected adults in need of a kidney transplant. The study will
also evaluate whether using both immunosuppressant drugs and MVC will improve kidney function
after a kidney transplant.

This study will enroll HIV-infected adults on combination antiretroviral therapy (cART) who
need a kidney transplant. At the time of their kidney transplant, study participants will be
randomly assigned to receive either MVC or placebo as an addition to their cART regimen. (MVC
or placebo will be provided by the study. However, the HIV medicines in their cART regimens
will not be provided by the study.) Participants will receive MVC or placebo throughout their
participation in the study, which will be 1 to 3 years depending on when they enroll in the
study.

Study visits will occur at enrollment (Day 0) and post-transplant Weeks 1, 2, 4, 8, 13, 26,
39, 52, 78, 104, 130, and 156. Study visits may include a physical examination, blood
collection, lymph node collection, urine sample collection, and a kidney biopsy. During the
study, participants will also be monitored closely for evidence of drug toxicities, HIV
treatment failure and rejection.

Inclusion Criteria:

- Participant is able to understand and provide informed consent.

- Documented HIV infection (by any licensed enzyme-linked immunosorbent assay [ELISA]
and confirmation by Western Blot, positive HIV antibody (ab) indirect fluorescent
antibody (IFA), or documented history of detectable HIV-1 RNA).

- Participant is 18 years of age or older.

- CD4+ T-cell count greater than or equal to 200/µL at any time in the 26 weeks prior to
enrollment.

- Most recent HIV-1 RNA less than 50 copies RNA/mL. Eligibility at the time of
enrollment will be determined based on the most recent HIV-1 RNA, not more than 26
weeks prior to enrollment. Subjects who require a switch in combination antiretroviral
therapy (cART) regimen to become study eligible must also have an eligible HIV-1 RNA
result post change in cART.

- Participant meets standard listing criteria for placement on transplant waiting list.

- For participants with an HIV+ deceased donor:

- No active opportunistic infections.

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

- Must be enrolled in an Institutional Review Board (IRB) approved research
protocol that fulfills the requirements of the DHHA Hope Act Policy (see the
protocol for more information).

- HIV+ deceased donor must have no evidence of invasive opportunistic complications
of HIV infection, and must have a pre-implant biopsy.

- Antiretroviral (ARV) Use: Participant is on a stable cART regimen for at least 3
months prior to enrollment (unless changes are made due to toxicity, drug
interactions, convenience or to an eligible non-protease inhibitor-based regimen).
Switch should not be due to virologic failure. A regimen consisting of 2 NTRTIs and an
integrase inhibitor is preferred due to minimal drug interaction but any non-protease
inhibitor regimen may be used.

- If on a protease inhibitor based regimen, participant must be switched to a
non-protease inhibitor-based regimen based on lack of any prior drug resistance
or antiretroviral-treatment failure, and be willing to remain on indefinitely
unless a change is medically necessary. Participants who need to be switched must
have been on a stable cART regimen for at least 3 months prior, and must have an
eligible HIV-1 RNA result post change in cART.

- If already on a stable non-protease inhibitor-based regimen, participant is
willing to remain on this regimen indefinitely unless a change in regimen is
medically indicated.

- If untreated, must initiate and be willing to remain on indefinitely a
non-protease inhibitor-based antiretroviral regimen unless a change is medically
necessary.

- No known allergy or intolerance to components of maraviroc (MVC) or its formulation.

- No known contraindication to MVC.

- Female participants of child-bearing potential must have a negative serum beta-human
chorionic gonadotropin (HCG) pregnancy test within 30 days of randomization.

Exclusion Criteria:

- Participant is currently on MVC.

- Participant needs multi-organ transplant.

- Participant has a live donor who is HIV+.

- Participant is unable to switch to a non-protease inhibitor-based cART regimen.

- Participant has received immunosuppressant medication in the 6 months prior to
enrollment. Note: Low dose maintenance steroids (less than or equal to 10 mg per day
of prednisone, or equivalent strength steroid) will not be considered
immunosuppression.

- Opportunistic Complication History: Any history of progressive multifocal
leukoencephalopathy (PML), chronic intestinal cryptosporidiosis of greater than 1
month duration, or primary central nervous system (CNS) lymphoma. Note: History of
pulmonary coccidiodomycosis will be treated per local site policy regarding this
infection in HIV negative transplant candidates, generally requiring a 5-year
disease-free interval.

- 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.

- Substance use that in the opinion of the investigator would interfere with compliance
with the study requirements.

- 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
local site practice. Women that become pregnant should not breastfeed.

- Participant has used interleukin-2 (IL-2) or granulocyte-macrophage colony-stimulating
factor (GM-CSF) in the prior six months.

- Participant has received interferon-alpha therapy in the prior 12 weeks.

- Use of investigational drugs within 4 weeks of enrollment.

- Past or current medical problems or findings from medical history, physical
examination, or laboratory testing that are not listed above, which, in the opinion of
the investigator, may pose additional risks from participation in the study, may
interfere with the participant's ability to comply with study requirements, or that
may impact the quality or interpretation of the data obtained from the study.