Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients
Condition: HIV Infections; Kidney Diseases
MeSH terms: Kidney Diseases
Intervention: Maraviroc; Placebo
Intervention description: Initial dose of 300 mg twice daily (150mg twice daily if co-prescribed with a potent CYP3A inhibitor or 600mg twice daily if co-prescribed with a potent CYP3A inducer). Will be modified if GFR < 30, if co-prescribed with a potent CYP3A inhibitor or inducer, or if the calcineurin inhibitor used for maintenance immunosuppression is changed to cyclosporine (which is only allowed for tacrolimus toxicity).
Once GFR is greater than or equal to 30, the dose should be returned to the non-renal dosage. If GFR is consistently fluctuating (especially immediately post-transplant), the site investigator may choose when to resume normal dosing of study product based on clinical assessment of stability.; Initial dose of 300 mg twice daily (150mg twice daily if co-prescribed with a potent CYP3A inhibitor or 600mg twice daily if co-prescribed with a potent CYP3A inducer). Will be modified if GFR < 30, if co-prescribed with a potent CYP3A inhibitor or inducer, or if the calcineurin inhibitor used for maintenance immunosuppression is changed to cyclosporine (which is only allowed for tacrolimus toxicity).
Once GFR is greater than or equal to 30, the dose should be returned to the non-renal dosage. If GFR is consistently fluctuating (especially immediately post-transplant), the site investigator may choose when to resume normal dosing of study product based on clinical assessment of stability.
Intervention MeSH terms: Maraviroc
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 97.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV-infected with end-stage kidney disease

Summary:

      Maraviroc (MVC) is a type of HIV medicine called a CCR5 inhibitor. This study will evaluate
      the safety and tolerability of MVC in HIV-infected adults receiving a kidney transplant.
    

Eligibility criteria:

        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 coccidioidomycosis 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.