Impact of Everolimus on HIV Persistence Post Kidney or Liver Transplant (HIVTR-EVE)

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
HIV; Kidney Transplant; Liver Transplant	Drug: everolimus	Phase 4

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).

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	10 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Impact of Everolimus on HIV Persistence Post Kidney (and Kidney/Pancreas) or Liver Transplant
Study Start Date :	February 2016
Estimated Primary Completion Date :	January 2018
Estimated Study Completion Date :	January 2018

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Everolimus	Drug: everolimus; Other Name: Zortress

Outcome Measures

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Primary Outcome Measures :

1. Change in frequency of CD4+ T cell-associated HIV-1 copy number [ Time Frame: 12 months ]
   6 months on study drugs + 6 months post discontinuation

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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).

Contacts and Locations

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Locations

United States, California
University of California, San Francisco
San Francisco, California, United States, 94143

Sponsors and Collaborators

University of California, San Francisco

More Information

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Responsible Party:	Peter Stock, Professor of Surgery, University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT02429869 History of Changes
Other Study ID Numbers:	HIVTR-EVE
First Posted:	April 29, 2015
Last Update Posted:	November 6, 2017
Last Verified:	October 2017

Additional relevant MeSH terms:

Everolimus; Sirolimus; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors	Physiological Effects of Drugs; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antifungal Agents