Impact of Everolimus on HIV Persistence Post Kidney or Liver Transplant

Official Title:

Impact of Everolimus on HIV Persistence Post Kidney (and Kidney/Pancreas) or Liver Transplant

Basic Trial Information

Phase Type Age Sponsor Protocol IDs Status
Phase 4 Interventional 18 Years and older University of California, San Francisco HIVTR-EVE
NCT02429869
Enrolling patients

Study Design:


Principal Investigator

Professor of Surgery
Surgical Director, Kidney and Pancreas Transplant Program
Surgical Director, Pediatric Renal Transplant Program
Co-Director, Pancreatic Islet Cell Transplant Program
Chair, Department of Surgery Research Committee
Director, T32 Training Program in Transplant Surgery

Clinical Research Coordinator

UCSF Medical Center at Parnassus
(415) 514-6454 Phone
(415) 476-6964 Fax

Trial Summary

Zortress (everolimus), the 40-O-(2-hydroxyethyl)-derivative of rapamycin, is an mTOR inhibitor approved for rejection prophylaxis in kidney transplant recipients. mTOR inhibition may favorably impact the HIV viral reservoir, and we hypothesize that adding everolimus to the transplant immunosuppressive regimen of HIV positive transplant recipients will decrease HIV persistence in CD4+ lymphocytes.

Eligibility

Inclusion Criteria:

     1. Solid organ (kidney, kidney/pancreas, or liver) transplant recipient
     2. Male or female ≥ 18 years of age.
     3. Documentation of HIV-1 infection diagnosis as evidenced by any licensed ELISA and
         confirmation by Western Blot, or documented history of detectable HIV-1 RNA)
     4. HIV-1 plasma RNA <50 copies/ml for at least 2 years with at least one measurement per
         year and most recent viral load within 16 weeks of enrollment and study drug
         initiation. Episodes of a single HIV plasma RNA 50 - 500 copies/ml will not exclude
         participation if the subsequent HIV plasma RNA was <50 copies/ml.
     5. CD4+ T cell counts greater than 200 cell/µl within 16 weeks of enrollment and study
         drug initiation.
     6. Receiving combination antiretroviral therapy (at least 3 agents)
     7. Written informed consent obtained from subject or subject's legal representative and
         ability for subject to comply with the requirements of the study.
Exclusion Criteria:

     1. Pregnant, breastfeeding, or unwilling to practice birth control during participation
         in the study.
     2. Presence of a condition or abnormality that in the opinion of the Investigator would
         compromise the safety of the patient or the quality of the data.
     3. Patients who are intending to modify antiretroviral therapy in the next 6 months for
         any reason.
     4. Serious illness requiring hospitalization or parenteral antibiotics within preceding
         3 months.
     5. A screening hemoglobin below 11.5 g/dL.
     6. A screening TSH consistent with hypothyroidism.
     7. Significant renal disease (eGFR < 60 ml/min) or acute nephritis
     8. Clinically active hepatitis as evidenced by clinical jaundice or Grade 2 or higher
         liver function test abnormalities.
     9. Hepatic cirrhosis or decompensated chronic liver disease.
     10. Concurrent treatment with immunomodulatory drugs, such an interferon-alpha, or
         exposure to any immunomodulatory drug in past 16 weeks (outside of standard
         immunosuppression).

Detailed Description

Open-label, single arm study that will enroll antiretroviral-treated HIV-infected adults who
are doing well post-liver or post-kidney transplant who are eligible and willing to add
everolimus to their immunosuppressive regimen (with a target trough level between 3-8
ng/ml). Calcineurin inhibitors will be decreased to obtain a 50% reduction in trough levels
with the addition of everolimus. Subjects will be maintained on that regimen for 6 months.
Biologic specimens for intensive immunology and virology studies will be obtained before,
during and after exposure to everolimus. Samples will be analyzed at screening, baseline
(prior to addition of everolimus), and at weeks 8 and 26 (while on everolimus), and week 52
(6 months post everolimus discontinuation).

Important

Final eligibility is determined by the health professionals conducting the trial and the protocol approved by the Committee on Human Resources (CHR) at the University of California, San Francisco (UCSF). The Patient Consent Form for this trial is available upon request. For more information about this trial, please see the full posting at ClinicalTrials.gov.

Information about this trial was obtained from the NIH Clinical Trials website, http://clinicaltrials.gov on 3/15/2017. UCSF specific information including the PI (Principal Investigator), trial enrollment status, and UCSF Study ID, supplement the ClinicalTrials.gov study posting.
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