Trial Outcomes & Findings for Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients (NCT NCT02741323)

NCT ID: NCT02741323

Last Updated: 2023-08-21

Results Overview

The primary efficacy endpoint is the 52-week GFR as measured by iohexol clearance

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

97 participants

Primary outcome timeframe

Measured at Week 52 Post-transplant

Results posted on

2023-08-21

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1: Maraviroc (MVC) Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo Participants who were assigned to and received Placebo in the study.
Overall Study STARTED	49	48
Overall Study COMPLETED	43	40
Overall Study NOT COMPLETED	6	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Maraviroc (MVC) n=49 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=48 Participants Participants who were assigned to and received Placebo in the study.	Total n=97 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	42 Participants n=5 Participants	42 Participants n=7 Participants	84 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Age, Continuous	51.6 years STANDARD_DEVIATION 10.8 • n=5 Participants	53.1 years STANDARD_DEVIATION 10.3 • n=7 Participants	52.3 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	43 Participants n=7 Participants	85 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants n=5 Participants	41 Participants n=7 Participants	85 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	39 Participants n=5 Participants	36 Participants n=7 Participants	75 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Unknown/ Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	49 participants n=5 Participants	48 participants n=7 Participants	97 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured at Week 52 Post-transplant

Population: Included Full Analysis Population participants with available 52-week GFR level

The primary efficacy endpoint is the 52-week GFR as measured by iohexol clearance

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=18 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=13 Participants Participants who were assigned to and received Placebo in the study.
Mean Glomerular Filtration Rate by Iohexol Clearance at Week 52	37.0 mL/min/1.73 m² Interval 30.1 to 43.9	40.1 mL/min/1.73 m² Interval 26.9 to 53.3

PRIMARY outcome

Timeframe: Measured through Week 52 Post-transplant

The primary safety endpoint will be the incidence of graft loss and toxicities ≥ Grade 3 and/or permanent treatment discontinuation within the first 52 weeks post-transplant

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=49 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=48 Participants Participants who were assigned to and received Placebo in the study.
Cumulative Incidence of Graft Loss, Toxicities ≥ Grade 3 Per the DAIDS Toxicity Table and/or Permanent Treatment Discontinuation	0.84 Proportion (KM estimate for incidence) Interval 0.72 to 0.93	0.85 Proportion (KM estimate for incidence) Interval 0.74 to 0.94

SECONDARY outcome

Timeframe: Measured at Week 26 Post-transplant

Population: Full Analysis Population

Based on the formalin-fixed paraffin-embedded (FFPE) kidney biopsy sample. CD45 RNA In Situ Hybridization was performed, and the CD45 gene expression count is calculated by counting the "spots" (the RNA signal) in QuPath and then dividing the number of spots by biopsy tissue area in mm².

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=15 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=10 Participants Participants who were assigned to and received Placebo in the study.
Mean CD45 Gene Expression Count (PTPRC)	49.4 spots/mm² Interval 12.3 to 129.0	50.9 spots/mm² Interval 16.2 to 518.0

SECONDARY outcome

Timeframe: Measured at Week 26 Post-transplant

Population: Full Analysis Population

Mean CD45 quantitative immunohistochemistry (IHC) based on FFPE sample

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=20 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=15 Participants Participants who were assigned to and received Placebo in the study.
Mean CD45 Quantitative Immunohistochemistry (IHC)	144.7 cells/mm² Interval 84.5 to 294.0	77.5 cells/mm² Interval 15.0 to 285.9

SECONDARY outcome

Timeframe: Measured at Week 26 Post-transplant

Population: Full Analysis Population - subset of participants with available data at 26 weeks.

Tissue Common Rejection Module (tCRM) score using the 11-gene tCRM module on FFPE biopsy shaves at 26 weeks. The score measures the average (geometric mean) gene expression level of CRM genes (BASP1, CD6, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, TAP1) in kidney tissue. Possible range (min-max) for the tCRM score is 0.01 - 15.0, with higher values representing worse outcomes.

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=23 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=21 Participants Participants who were assigned to and received Placebo in the study.
Tissue Common Rejection Module (tCRM) Score Using the 11-gene tCRM Module on FFPE Biopsy Shaves	1.83 score on a scale Interval 1.09 to 3.36	1.67 score on a scale Interval 1.14 to 2.16

SECONDARY outcome

Timeframe: Measured at Week 26 Post-transplant

Population: Full Analysis Population - subset of participants with available data at Week 26

Urine Common Rejection Module (uCRM) score using the 11-gene uCRM module on urine cell pellets at week 26. The score measures the average (geometric mean) gene expression level of CRM genes (BASP1, CD6, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, TAP1) in urine sediment. Possible range (min-max) for the uCRM score is 0.01 - 15.0, with higher values representing worse outcomes.

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=24 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=21 Participants Participants who were assigned to and received Placebo in the study.
Urine Common Rejection Module (uCRM) Score Using the 11-gene uCRM Module on Urine Cell Pellets	0.48 score on a scale Interval 0.23 to 1.08	0.42 score on a scale Interval 0.2 to 0.87

SECONDARY outcome

Timeframe: Measured at Week 52 Post-transplant

Population: Full Analysis Population - subset of participants with available data at Week 52

Urine Common Rejection Module (uCRM) score using the 11-gene uCRM module on urine cell pellets at week 52. The score measures the average (geometric mean) gene expression level of CRM genes (BASP1, CD6, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, TAP1) in urine sediment. Possible range (min-max) for the uCRM score is 0.01 - 15.0, with higher values representing worse outcomes.

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=21 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=17 Participants Participants who were assigned to and received Placebo in the study.
Urine Common Rejection Module (uCRM) Score Using the 11-gene uCRM Module on Urine Cell Pellets	0.40 score on a scale Interval 0.12 to 0.85	0.25 score on a scale Interval 0.16 to 0.64

SECONDARY outcome

Timeframe: Measured at Week 52 Post-transplant

Population: Full Analysis Population participants with available data at Week 52.

Measured by Chronic Kidney Disease Epidemiology collaboration equation (CKD-EPI) Creatinine equation

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=44 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=37 Participants Participants who were assigned to and received Placebo in the study.
Proportion of Participants With Estimated Glomerular Filtration Rate (eGFR) Less Than 60 mL/Min/1.73 m² at Week 52	0.45 Proportion Interval 0.33 to 0.63	0.73 Proportion Interval 0.6 to 0.89

SECONDARY outcome

Timeframe: Year 1 time point

Population: Participants in the Full Analysis population with available data at Year 1

Proportion of participants with defined CKD stage 4 or 5 at week 52 post-transplant. CKD Stage 4 or 5 is defined as a glomerular filtration rate (GFR) of \<30 mL/min.

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=44 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=37 Participants Participants who were assigned to and received Placebo in the study.
Proportion of Participants With Defined CKD Stage 4 or 5 at Year 1	0.07 Proportion of participants Interval 0.02 to 0.2	0.14 Proportion of participants Interval 0.06 to 0.31

SECONDARY outcome

Timeframe: Measured at Week 52 Post-transplant

Population: Full Analysis Population participants with available data at Week 52

Mean eGFR at Week 52 calculated by CKD-EPI creatinine equation

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=44 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=37 Participants Participants who were assigned to and received Placebo in the study.
Mean eGFR at Week 52 Based on CKD-EPI Creatinine Equation	59.2 mL/min/1.73 m² Interval 53.2 to 65.2	49.3 mL/min/1.73 m² Interval 43.5 to 55.1

SECONDARY outcome

Timeframe: Time points in Year 1 (four time points: weeks 13, 26, 39, 52)

Population: Participants from the Full Analysis Population with available eGFR data in Year 1.

The slope of eGFR over time in Year 1, calculated by CKD-EPI Creatinine equation. Slope is computed via the repeated measures analysis, covering the study time points of weeks 13, 26, 39 and 52. The estimated average slope (and corresponding 95% confidence interval) is provided for incremental progression from one time point to the next (i.e., the displayed slope shows the extent of increase (positive) or decrease (negative) in eGFR level per every time point (13 weeks) elapsed.

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=47 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=42 Participants Participants who were assigned to and received Placebo in the study.
The Slope of eGFR Over Time in Year 1	-0.1 mL/min/1.73 m² per 13 weeks Interval -1.6 to 1.5	-0.5 mL/min/1.73 m² per 13 weeks Interval -2.2 to 1.2

SECONDARY outcome

Timeframe: At week 52 post-transplant

Population: Full Analysis Population

HIV DNA in peripheral blood CD4+ T cells at Week 52. The standard ACTG type extraction protocol was used to extract DNA from PBMC. The readout was copies of cellular HIV-1 DNA per million PBMC. Subsequently, the outcome measure/value was obtained by multiplying the readout by the participant's CD4 percentage level at that time point, to obtain the measure of copies of HIV-1 DNA per million peripheral blood CD4+ T cells

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=33 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=24 Participants Participants who were assigned to and received Placebo in the study.
HIV DNA in Peripheral Blood CD4+ T Cells at Week 52	22.2 copies of HIV-1 DNA/million CD4+ T cells Interval 4.1 to 68.4	43.9 copies of HIV-1 DNA/million CD4+ T cells Interval 12.6 to 89.4

SECONDARY outcome

Timeframe: Week 52 Post Transplant

Population: Full Analysis Population

HIV RNA in peripheral blood CD4+ T cells at Week 52. The standard ACTG type extraction protocol was used to extract RNA from PBMC. The readout was copies of cellular HIV-1 RNA per million PBMC. Subsequently, the outcome measure/value was obtained by multiplying the readout by the participant's CD4 percentage level at that time point, to obtain the measure of copies of HIV-1 RNA per million peripheral blood CD4+ T cells

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=24 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=22 Participants Participants who were assigned to and received Placebo in the study.
HIV RNA in Peripheral Blood CD4+ T Cells at Week 52.	402.1 copies of HIV-1 RNA/million CD4+ T cells Interval 43.5 to 2631.8	902.6 copies of HIV-1 RNA/million CD4+ T cells Interval 191.3 to 5788.3

SECONDARY outcome

Timeframe: Week 52 Post-transplant

Population: Full Analysis Population

Plasma HIV RNA levels (single copy assay) at Week 52 Post-transplant

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=29 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=28 Participants Participants who were assigned to and received Placebo in the study.
Plasma HIV RNA Levels (Single Copy Assay) at Week 52	0 copies of HIV-1 RNA/mL Interval 0.0 to 1.3	0.3 copies of HIV-1 RNA/mL Interval 0.0 to 0.6

SECONDARY outcome

Timeframe: Within Year 1 Post-transplant

Population: Full Analysis Population

Defined by histologic evidence of rejection and graft dysfunction as identified on central read of biopsy slides as well as on site biopsies. When a central read of biopsy slide is available, those results will be used; in its absence, site biopsy result will be used. Both acute cellular and humoral rejections were considered for this outcome measure, but borderline results were excluded.

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=49 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=48 Participants Participants who were assigned to and received Placebo in the study.
Cumulative Incidence/Proportion of Biopsy Proven Acute Rejection Within 1 Year Post Transplant	0.0816 Proportion of participants Interval 0.0319 to 0.2088	0.1250 Proportion of participants Interval 0.0591 to 0.2642

SECONDARY outcome

Timeframe: Within 3 years post-transplant

Population: Full Analysis Population

Measured by the Banff 2007 criteria as identified on central read of biopsy slides; for site biopsy results, grading was not available, all results except for borderline results were assumed to be grade 1A or greater. If available, central read result was used; if not, site biopsy result was used.

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=49 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=48 Participants Participants who were assigned to and received Placebo in the study.
Cumulative Incidence/Proportion of Acute Cellular Rejection Grade Equal to or Greater Than 1A During the Entire Study Follow-up	0.1224 Proportion of participants Interval 0.0579 to 0.2591	0.1429 Proportion of participants Interval 0.072 to 0.2836

SECONDARY outcome

Timeframe: Within 52 weeks post transplant

Population: Full Analysis Population

Incidence of humoral/antibody mediated rejection within 52 weeks of the transplant. Both central reads and site biopsy results were included, and central read result was used if one was available, and if not, the site biopsy result was used.

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=49 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=48 Participants Participants who were assigned to and received Placebo in the study.
Incidence/Proportion of Antibody Mediated Rejection	0.0000 Proportion of participants Interval 0.0 to Upper 95% Confidence Limit was not estimable.	0.0208 Proportion of participants Interval 0.003 to 0.1449

SECONDARY outcome

Timeframe: Measured at Week 52

Population: Full Analysis Population with participants contributing data to week 52 time point

Proportion of participants with de novo anti-donor human leukocyte antigen (HLA) antibodies at Week 52

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=25 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=23 Participants Participants who were assigned to and received Placebo in the study.
Proportion of Participants With de Novo Anti-donor Human Leukocyte Antigen (HLA) Antibodies	0.1600 Proportion of participants Interval 0.0652 to 0.3928	0.0870 Proportion of participants Interval 0.0231 to 0.3269

SECONDARY outcome

Timeframe: Month 6 Post-transplant

Population: Full Analysis Population

Histology/in situ hybridization was used to assess HIV infection in the renal allograft and calculate the proportion of participants with HIV infection

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=15 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=10 Participants Participants who were assigned to and received Placebo in the study.
Incidence/Proportion of Participants With HIV Infection in the Renal Allograft	0 Proportion of participants Interval 0.0 to Upper 95% Confidence Limit was not estimable	0 Proportion of participants Interval 0.0 to Upper 95% Confidence Limit was not estimable

SECONDARY outcome

Timeframe: Within Year 1 Post-transplant

Population: Full Analysis Population

Incidence of death within Year 1 post-transplant

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=49 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=48 Participants Participants who were assigned to and received Placebo in the study.
Incidence of Death at Year 1	4.3 Percent (KM estimate for incidence) Interval 1.1 to 16.3	2.2 Percent (KM estimate for incidence) Interval 0.3 to 14.7

SECONDARY outcome

Timeframe: Within Year 1 Post-transplant

Population: Full Analysis Population

Incidence of graft loss within Year 1 post-transplant.

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=49 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=48 Participants Participants who were assigned to and received Placebo in the study.
Incidence of Graft Loss in Year 1	6.3 Percent (KM estimate for incidence) Interval 2.1 to 18.2	6.6 Percent (KM estimate for incidence) Interval 2.2 to 19.0

SECONDARY outcome

Timeframe: Within Year 1 Post-transplant

Population: Full Analysis Population

Incidence of all adverse events (AEs) greater than or equal to Grade 3 within 1 year post-transplant

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=49 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=48 Participants Participants who were assigned to and received Placebo in the study.
Incidence of All Adverse Events (AEs) Greater Than or Equal to Grade 3 at Year 1	81.6 Percent (KM estimate for incidence) Interval 69.8 to 90.9	77.6 Percent (KM estimate for incidence) Interval 64.9 to 88.2

SECONDARY outcome

Timeframe: Within Year 1 Post-transplant

Population: Full Analysis Population

Incidence of serious adverse events (SAEs) greater than or equal to Grade 3 within 1 year post-transplant

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=49 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=48 Participants Participants who were assigned to and received Placebo in the study.
Incidence of Serious Adverse Events (SAEs) Greater Than or Equal to Grade 3 Within Year 1	73.5 Percent (KM estimate for incidence) Interval 60.7 to 84.8	53.2 Percent (KM estimate for incidence) Interval 39.8 to 68.0

SECONDARY outcome

Timeframe: Within Year 1 Post-transplant

Population: Full Analysis Population

Incidence of opportunistic infections or neoplasms within 1 year post-transplant

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=49 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=48 Participants Participants who were assigned to and received Placebo in the study.
Incidence of Opportunistic Infections or Neoplasms Within Year 1	19.1 Percent (KM estimate for incidence) Interval 10.4 to 33.5	6.7 Percent (KM estimate for incidence) Interval 2.2 to 19.4

SECONDARY outcome

Timeframe: Within Year 1 Post-transplant

Population: Full Analysis Population

Incidence of non-opportunistic infections requiring hospitalization within 1 year post-transplant

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=49 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=48 Participants Participants who were assigned to and received Placebo in the study.
Incidence of Non-opportunistic Infections Requiring Hospitalization Within Year 1	21.3 Percent (KM estimate for incidence) Interval 12.1 to 36.1	28.6 Percent (KM estimate for incidence) Interval 17.7 to 44.2

SECONDARY outcome

Timeframe: Month 3 Post-transplant (0-12 hours post-dose)

Population: PK Analysis Population: Subset of Participants Enrolled at UCSF

Calcineurin inhibitor (tacrolimus) trough levels, from 0-12 hours post-dose at month 3 post-transplant for a subset of participants enrolled at UCSF

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=8 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=5 Participants Participants who were assigned to and received Placebo in the study.
Calcineurin Inhibitor (Tacrolimus) Trough Levels for Participants on Maraviroc Versus Placebo	9.70 nM Interval 8.56 to 12.3	12.10 nM Interval 11.6 to 12.7

SECONDARY outcome

Timeframe: Month 3 Post-transplant (0-12 hours post-dose)

Population: PK Analysis Population: Subset of participants enrolled at UCSF

Calcineurin inhibitor (tacrolimus) AUC, 0-12 hours post-dose at month 3 post-transplant for a subset of participants enrolled at UCSF

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=8 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=5 Participants Participants who were assigned to and received Placebo in the study.
Calcineurin Inhibitor (Tacrolimus) AUC for Participants on Maraviroc Versus Placebo	191.17 nmol-h/L Interval 160.0 to 210.14	193.22 nmol-h/L Interval 190.78 to 206.82

SECONDARY outcome

Timeframe: Month 3 Post-transplant (0-12 hours post-dose)

Population: PK Analysis Population: Maraviroc recipients in a subset of participants enrolled at UCSF

AUC of CCR5 blockade (maraviroc), 0-12 hours post-dose at month 3 post-transplant in a subset of participants enrolled at UCSF

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=8 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo Participants who were assigned to and received Placebo in the study.
AUC of CCR5 Blockade (Maraviroc)	3101.82 nmol-h/L Interval 2700.76 to 5892.17	—

SECONDARY outcome

Timeframe: Month 3 Post-transplant (0-12 hours post-dose)

Population: PK Analysis Population: Maraviroc recipients in a subset of participants enrolled at UCSF

Trough levels of CCR5 blockade (maraviroc) from 0-12 hours post-dose testing at month 3 post-transplant in a subset of participants enrolled at UCSF

Outcome measures

Outcome measures
Measure	Arm 1: Maraviroc (MVC) n=8 Participants Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo Participants who were assigned to and received Placebo in the study.
Trough Levels of CCR5 Blockade (Maraviroc)	90.95 nM Interval 73.75 to 170.0	—

Adverse Events

Arm 1: Maraviroc (MVC)

Serious events: 37 serious events

Other events: 28 other events

Deaths: 5 deaths

Arm 2: Placebo

Serious events: 34 serious events

Other events: 37 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Arm 1: Maraviroc (MVC) n=49 participants at risk Participants who were assigned to and received Maraviroc in the study.	Arm 2: Placebo n=48 participants at risk Participants who were assigned to and received Placebo in the study.
Immune system disorders Transplant rejection	10.2% 5/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	4.2% 2/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.
Infections and infestations COVID-19 pneumonia	8.2% 4/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	6.2% 3/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.
Infections and infestations Pyelonephritis	6.1% 3/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	6.2% 3/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.
Infections and infestations Urinary tract infection	4.1% 2/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	12.5% 6/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.
Investigations Blood creatinine increased	24.5% 12/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	14.6% 7/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.
Investigations Blood glucose increased	16.3% 8/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	12.5% 6/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.
Investigations Glomerular filtration rate abnormal	10.2% 5/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	14.6% 7/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.
Investigations Haemoglobin decreased	28.6% 14/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	22.9% 11/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.
Investigations Lymphocyte count decreased	6.1% 3/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	10.4% 5/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.
Metabolism and nutrition disorders Hyperglycaemia	2.0% 1/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	14.6% 7/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.
Renal and urinary disorders Acute kidney injury	6.1% 3/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	10.4% 5/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.
Renal and urinary disorders Haematuria	6.1% 3/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	4.2% 2/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.
Vascular disorders Hypertension	10.2% 5/49 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.	8.3% 4/48 • Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade: * Postural hypotension * Allergic reaction * Rash * HIV persistent virologic failure defined as an HIV viral load \>1000 copies/mL for more than 90 days that is not the result of an investigator/physician approved interruption in antiretroviral treatment.

Additional Information

Clinical Research Manager

University of California, San Francisco

Phone: 415-595-1226

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place