HIVPhase 4HIVTR-EVENCT02429869
Impact of Everolimus on HIV Persistence Post Kidney or Liver Transplant
A Phase 4 study testing everolimus in people with HIV and Kidney Transplant, run by University of California, San Francisco at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV, Kidney Transplant, Liver Transplant
- What is being tested?
- everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Feb 2016to 31 Jan 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Solid organ (kidney, kidney/pancreas, or liver) transplant recipient
- Male or female ≥ 18 years of age.
- 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)
- 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.
- CD4+ T cell counts greater than 200 cell/µl within 16 weeks of enrollment and study drug initiation.
- Receiving combination antiretroviral therapy (at least 3 agents)
- Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
Who cannot join
- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
- 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.
- Patients who are intending to modify antiretroviral therapy in the next 6 months for any reason.
- Serious illness requiring hospitalization or parenteral antibiotics within preceding 3 months.
- A screening hemoglobin below 11.5 g/dL.
- A screening TSH consistent with hypothyroidism.
Show all 10Show fewer
- Significant renal disease (eGFR < 60 ml/min) or acute nephritis
- Clinically active hepatitis as evidenced by clinical jaundice or Grade 2 or higher liver function test abnormalities.
- Hepatic cirrhosis or decompensated chronic liver disease.
- Concurrent treatment with immunomodulatory drugs, such an interferon-alpha, or exposure to any immunomodulatory drug in past 16 weeks (outside of standard immunosuppression).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: Impact of Everolimus on HIV Persistence Post Kidney (and Kidney/Pancreas) or Liver Transplant
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.
Read the 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).
- Conditions
- HIV, Kidney Transplant, Liver Transplant
- Being tested
- everolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called Zortress
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Experimental | Not described Receives: Drug: everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cell-associated HIV DNA
Peripheral blood mononuclear cells were isolated from whole blood using the Ficoll density gradient technique. Peripheral blood CD4 T cells were enriched by negative selection using antibody-coupled magnetic beads (Stem Cell Technologies) prior to simultaneous RNA and DNA isolation using cell-sparing protocols (AllPrep, Qiagen). Bulk CD4+ T cell or PBMC-associated HIV DNA and unspliced RNA were quantified using real-time PCR methods.The primer and probe sequences targeted conserved regions to enable quantification of a broad range of HIV subtypes. Values were normalized to DNA quantification of a human housekeeping gene (CCR5) in order to determine nucleic acid copies per million CD4+ T cell or PBMC as described. In addition to traditional quantitative PCR, a novel single-cell-in-droplet (scd)PCR method was used to quantify the absolute number or frequency of individual purified CD4+ T cells that express unspliced HIV RNA.
Measured: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)
Secondary outcomes (2)
Cell-associated Total HIV RNA
Peripheral blood mononuclear cells were isolated from whole blood using the Ficoll density gradient technique. Peripheral blood CD4 T cells were enriched by negative selection using antibody-coupled magnetic beads (Stem Cell Technologies) prior to simultaneous RNA and DNA isolation using cell-sparing protocols (AllPrep, Qiagen). Bulk CD4+ T cell or PBMC-associated HIV DNA and unspliced RNA were quantified using real-time PCR methods.The primer and probe sequences targeted conserved regions to enable quantification of a broad range of HIV subtypes. Values were normalized to DNA quantification of a human housekeeping gene (CCR5) in order to determine nucleic acid copies per million CD4+ T cell or PBMC as described. In addition to traditional quantitative PCR, a novel single-cell-in-droplet (scd)PCR method was used to quantify the absolute number or frequency of individual purified CD4+ T cells that express unspliced HIV RNA.
Measured: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)
Plasma HIV RNA
Plasma HIV RNA was quantified in a highly sensitive single-copy assay (SCA) using repetitive sampling in the Panther system (Hologic) at the Blood Systems Research Institute. Up to 18 replicates were tested for each sample in order to determine plasma RNA levels as low as 0.18 copies/mL.
Measured: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2015 (estimated)
- Study start24 Feb 2016
- Primary completion31 Jan 2018
- Study completion31 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- amfAR, The Foundation for AIDS Research, Novartis
- Responsible party
- Principal investigator, Peter Stock, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02429869
- Sponsor's protocol ID
- HIVTR-EVE
- Acronym
- HIVTR-EVE
- Status last verified
- Oct 2019
- First submitted
- 24 Apr 2015
- Last updated
- 19 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 32780519
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Everolimus on HIV Persistence Post Kidney (and Kidney/Pancreas) or Liver Transplant
- ClinicalTrials.gov ID
- NCT02429869
- Acronym / sponsor ID
- HIVTR-EVE / HIVTR-EVE
- Conditions
- HIV, Kidney Transplant, Liver Transplant
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- amfAR, The Foundation for AIDS Research, Novartis
- Study start
- 24 Feb 2016 (actual)
- Primary completion
- 31 Jan 2018 (actual)
- Study completion
- 31 Jan 2018 (actual)
- First posted
- 29 Apr 2015 (estimated)
- Results
- Posted 19 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Experimental | Drug: everolimus |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Solid organ (kidney, kidney/pancreas, or liver) transplant recipient
- Male or female ≥ 18 years of age.
- 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)
- 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.
- CD4+ T cell counts greater than 200 cell/µl within 16 weeks of enrollment and study drug initiation.
Key exclusion criteria (10 listed)
- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
- 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.
- Patients who are intending to modify antiretroviral therapy in the next 6 months for any reason.
- Serious illness requiring hospitalization or parenteral antibiotics within preceding 3 months.
- A screening hemoglobin below 11.5 g/dL.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusAlso: Zortress | Drug | Everolimus |
Primary outcome
Cell-associated HIV DNA
Time frame: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)
Peripheral blood mononuclear cells were isolated from whole blood using the Ficoll density gradient technique. Peripheral blood CD4 T cells were enriched by negative selection using antibody-coupled magnetic beads (Stem Cell Technologies) prior to simultaneous RNA and DNA isolation using cell-sparing protocols (AllPrep, Qiagen). Bulk CD4+ T cell or PBMC-associated HIV DNA and unspliced RNA were quantified using real-time PCR methods.The primer and probe sequences targeted conserved regions to enable quantification of a broad range of HIV subtypes. Values were normalized to DNA quantification of a human housekeeping gene (CCR5) in order to determine nucleic acid copies per million CD4+ T cell or PBMC as described. In addition to traditional quantitative PCR, a novel single-cell-in-droplet (scd)PCR method was used to quantify the absolute number or frequency of individual purified CD4+ T cells that express unspliced HIV RNA.
2 secondary outcomes
Cell-associated Total HIV RNA
Time frame: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)
Plasma HIV RNA
Time frame: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32780519Henrich 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing everolimus in people with HIV and Kidney Transplant, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cell-associated HIV DNA (time frame: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02429869, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2019.