Impact of Everolimus on HIV Persistence Post Kidney or Liver Transplant

• Status: Completed
• Trial end date: 2018-01-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborators: amfAR, The Foundation for AIDS Research; Novartis
• Treatments: Everolimus; Sirolimus

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).