Clinical trial NCT02429869: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Kidney Transplant
Liver Transplant
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: amfAR, The Foundation for AIDS Research
name: Novartis
First posted: 2015-04-29
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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).

Eligibility 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).

Primary outcomes:
measure: Cell-associated HIV DNA
timeFrame: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)
Secondary outcomes:
measure: Cell-associated Total HIV RNA
timeFrame: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)
measure: Plasma HIV RNA
timeFrame: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
References:
citation: Henrich TJ, Schreiner C, Cameron C, Hogan LE, Richardson B, Rutishauser RL, Deitchman AN, Chu S, Rogers R, Thanh C, Gibson EA, Zarinsefat A, Bakkour S, Aweeka F, Busch MP, Liegler T, Baker C, Milush J, Deeks SG, Stock PG. Everolimus, an mTORC1/2 inhibitor, in ART-suppressed individuals who received solid organ transplantation: A prospective study. Am J Transplant. 2021 May;21(5):1765-1779. doi: 10.1111/ajt.16244. Epub 2020 Sep 15.