Trial Outcomes & Findings for Impact of Everolimus on HIV Persistence Post Kidney or Liver Transplant (NCT NCT02429869)
NCT ID: NCT02429869
Last Updated: 2019-11-19
Results Overview
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.
COMPLETED
PHASE4
10 participants
Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)
2019-11-19
Participant Flow
Ten HIV-infected adult solid organ transplant participants on stable ART and were taking non-mTOR based immune suppressive regimens for allograft rejection were recruited at the University of California, San Francisco in this open label, single-arm everolimus trial.
Participant milestones
| Measure |
Everolimus
Subjects on mTOR inhibitor (everolimus) for 6 months, added to standard of care immunosuppressive regimen
|
|---|---|
|
Overall Study
STARTED
|
10
|
|
Overall Study
COMPLETED
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Impact of Everolimus on HIV Persistence Post Kidney or Liver Transplant
Baseline characteristics by cohort
| Measure |
Everolimus
n=10 Participants
Subjects on mTOR inhibitor (everolimus) for 6 months, added to standard of care immunosuppressive regimen
|
|---|---|
|
Age, Continuous
|
58.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)Population: CD4+ T Cell count was not collected at Month 6 for one participant who did not show up for the visit.
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.
Outcome measures
| Measure |
Everolimus
n=10 Participants
This is a single arm study. Subjects on mTOR inhibitor (everolimus) for 6 months, added to standard of care immunosuppressive regimen
|
|---|---|
|
Cell-associated HIV DNA
Baseline
|
35 nucleic acid copies per million cells
Interval 8.0 to 173.0
|
|
Cell-associated HIV DNA
Month 2
|
43 nucleic acid copies per million cells
Interval 21.0 to 417.0
|
|
Cell-associated HIV DNA
Month 6
|
81 nucleic acid copies per million cells
Interval 28.0 to 210.0
|
|
Cell-associated HIV DNA
Month 12
|
16 nucleic acid copies per million cells
Interval 9.0 to 804.0
|
SECONDARY outcome
Timeframe: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)Population: CD4+ T Cell count was not collected at Month 6 for one participant who did not show up for the visit.
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.
Outcome measures
| Measure |
Everolimus
n=10 Participants
This is a single arm study. Subjects on mTOR inhibitor (everolimus) for 6 months, added to standard of care immunosuppressive regimen
|
|---|---|
|
Cell-associated Total HIV RNA
Baseline HIV RNA CD4+
|
423 nucleic acid copies per million cells
Interval 148.0 to 1702.0
|
|
Cell-associated Total HIV RNA
Month 2 HIV RNA CD4+
|
310 nucleic acid copies per million cells
Interval 228.0 to 789.0
|
|
Cell-associated Total HIV RNA
Month 6 HIV RNA CD4+
|
702 nucleic acid copies per million cells
Interval 417.0 to 1299.0
|
|
Cell-associated Total HIV RNA
Month 12 HIV RNA CD4+
|
354 nucleic acid copies per million cells
Interval 165.0 to 633.0
|
SECONDARY outcome
Timeframe: Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)Population: CD4+ T Cell count was not collected at Month 6 for one participant who did not show up for the visit.
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.
Outcome measures
| Measure |
Everolimus
n=10 Participants
This is a single arm study. Subjects on mTOR inhibitor (everolimus) for 6 months, added to standard of care immunosuppressive regimen
|
|---|---|
|
Plasma HIV RNA
Baseline
|
0.291 nucleic acid copies per million cells
Interval 0.0 to 0.9283
|
|
Plasma HIV RNA
Month 2
|
0.584 nucleic acid copies per million cells
Interval 0.0 to 1.547
|
|
Plasma HIV RNA
Month 6
|
1.042 nucleic acid copies per million cells
Interval 0.189 to 2.05
|
|
Plasma HIV RNA
Month 12
|
0.941 nucleic acid copies per million cells
Interval 0.191 to 1.576
|
Adverse Events
Everolimus
Serious adverse events
| Measure |
Everolimus
n=10 participants at risk
Subjects on mTOR inhibitor (everolimus) for 6 months, added to standard of care immunosuppressive regimen
|
|---|---|
|
Gastrointestinal disorders
Gastritis
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
10.0%
1/10 • Number of events 1 • 1 year
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place