Trial Outcomes & Findings for A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Maraviroc Therapy (NCT NCT00870363)
NCT ID: NCT00870363
Last Updated: 2017-05-30
Results Overview
immunohistochemistry for CD3+/CD4+ cells counted manually within the lamina propria
COMPLETED
PHASE4
44 participants
Baseline and nine months for 3 treatment cohorts and Baseline for the control group, which was only assessed at one time point
2017-05-30
Participant Flow
Participant milestones
| Measure |
Maraviroc in Combination With 2 NRTIs
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food taken in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Maraviroc PLUS Raltegravir in Combination With 2 NRTIs
maraviroc PLUS raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc plus raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food PLUS raltegravir 400mg 1 tablet taken twice a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Efavirenz or Other NNRTI With 2 NRTIs
efavirenz or other NNRTI (non-nucleoside reverse transcriptase inhibitor) in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
efavirenz \[or other NNRTI (non-nucleoside reverse transcriptase inhibitor)\]: efavirenz 600mg 1 capsule is taken once a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
HIV Negative Controls Not on ART
HIV-negative
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
11
|
11
|
12
|
|
Overall Study
COMPLETED
|
10
|
8
|
8
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
3
|
3
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Maraviroc Therapy
Baseline characteristics by cohort
| Measure |
Maraviroc in Combination With 2 NRTIs
n=10 Participants
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food taken in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Maraviroc PLUS Raltegravir in Combination With 2 NRTIs
n=8 Participants
maraviroc PLUS raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc plus raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food PLUS raltegravir 400mg 1 tablet taken twice a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Efavirenz or Other NNRTI With 2 NRTIs
n=8 Participants
efavirenz or other NNRTI (non-nucleoside reverse transcriptase inhibitor) in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
efavirenz \[or other NNRTI (non-nucleoside reverse transcriptase inhibitor)\]: efavirenz 600mg 1 capsule is taken once a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
HIV Negative Controls Not on ART
n=12 Participants
HIV-negative
|
Total
n=38 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
38 years
n=5 Participants
|
35 years
n=7 Participants
|
37 years
n=5 Participants
|
35 years
n=4 Participants
|
37 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
29 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
8 participants
n=7 Participants
|
8 participants
n=5 Participants
|
12 participants
n=4 Participants
|
38 participants
n=21 Participants
|
|
CD4 T-Cell count
|
441 CELLS/MM^3
n=5 Participants
|
453 CELLS/MM^3
n=7 Participants
|
322 CELLS/MM^3
n=5 Participants
|
NA CELLS/MM^3
n=4 Participants
|
436 CELLS/MM^3
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline and nine months for 3 treatment cohorts and Baseline for the control group, which was only assessed at one time pointPopulation: numbers represent an increase from baseline for the 3 treatment cohorts and represent the absolute value for the control group who were only measured at one timepjoint.
immunohistochemistry for CD3+/CD4+ cells counted manually within the lamina propria
Outcome measures
| Measure |
Maraviroc in Combination With 2 NRTIs
n=10 Participants
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food taken in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Maraviroc PLUS Raltegravir in Combination With 2 NRTIs
n=8 Participants
maraviroc PLUS raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc plus raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food PLUS raltegravir 400mg 1 tablet taken twice a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Efavirenz or Other NNRTI With 2 NRTIs
n=8 Participants
efavirenz or other NNRTI (non-nucleoside reverse transcriptase inhibitor) in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
efavirenz \[or other NNRTI (non-nucleoside reverse transcriptase inhibitor)\]: efavirenz 600mg 1 capsule is taken once a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
HIV Negative Controls Not on ART
n=12 Participants
HIV-negative
|
|---|---|---|---|---|
|
Change in the Density of CD3+/CD4+ Cells Per Cubic Millimeter at the Effector Sites in the Duodenal Tissues Following Antiretroviral Therapy Regimen
|
24 cells/mm^2
Interval -44.0 to 92.0
|
89 cells/mm^2
Interval 51.0 to 127.0
|
119 cells/mm^2
Interval -7.0 to 245.0
|
566 cells/mm^2
Interval 509.0 to 688.0
|
SECONDARY outcome
Timeframe: nine monthsPopulation: HIV negative controls were not on ART and did not have drug levels measured.
The reported drug level is for the primary ART agent for that cohort. For the maraviroc arm, maraviroc plasma and tissue levels are reported. For the maraviroc plus raltegravir arm, the raltegravir plasma and tissue levels are reported. For the efavirenz arm, the efavirenz plasma and tissue levels are reported. HIV negative controls were not on ART and did not have drug levels measured.
Outcome measures
| Measure |
Maraviroc in Combination With 2 NRTIs
n=10 Participants
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food taken in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Maraviroc PLUS Raltegravir in Combination With 2 NRTIs
n=8 Participants
maraviroc PLUS raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc plus raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food PLUS raltegravir 400mg 1 tablet taken twice a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Efavirenz or Other NNRTI With 2 NRTIs
n=8 Participants
efavirenz or other NNRTI (non-nucleoside reverse transcriptase inhibitor) in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
efavirenz \[or other NNRTI (non-nucleoside reverse transcriptase inhibitor)\]: efavirenz 600mg 1 capsule is taken once a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
HIV Negative Controls Not on ART
HIV-negative
|
|---|---|---|---|---|
|
Trough Plasma and Tissue Drug Levels in Volunteers at the Time of the Upper Endoscopy
plasma primary ART
|
94.5 ng/mL
Interval 60.5 to 126.5
|
397 ng/mL
Interval 93.4 to 1131.3
|
2459 ng/mL
Interval 1485.7 to 5328.2
|
—
|
|
Trough Plasma and Tissue Drug Levels in Volunteers at the Time of the Upper Endoscopy
duodenal tissue primary ART
|
0.7 ng/mL
Interval 0.3 to 1.4
|
0.1 ng/mL
Interval 0.07 to 0.3
|
11.1 ng/mL
Interval 8.4 to 15.0
|
—
|
SECONDARY outcome
Timeframe: Baseline and nine monthsPopulation: HIV negative controls did not have HIV-DNA in blood or tissue
single-cell suspension of digested duodenal tissue and Ficol-Hypaque separated PBMC underwent HIV-DNA PCR
Outcome measures
| Measure |
Maraviroc in Combination With 2 NRTIs
n=10 Participants
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food taken in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Maraviroc PLUS Raltegravir in Combination With 2 NRTIs
n=8 Participants
maraviroc PLUS raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc plus raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food PLUS raltegravir 400mg 1 tablet taken twice a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Efavirenz or Other NNRTI With 2 NRTIs
n=8 Participants
efavirenz or other NNRTI (non-nucleoside reverse transcriptase inhibitor) in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
efavirenz \[or other NNRTI (non-nucleoside reverse transcriptase inhibitor)\]: efavirenz 600mg 1 capsule is taken once a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
HIV Negative Controls Not on ART
HIV-negative
|
|---|---|---|---|---|
|
Change in HIV DNA Per 10^6 Cells in Duodenal Tissue Versus PBMC by Drug Regimen Received
PBMC HIV-DNA
|
-1709 copies/10^6 cells
Interval -2845.0 to -573.0
|
-2500 copies/10^6 cells
Interval -4868.0 to -132.0
|
-1330 copies/10^6 cells
Interval -5354.0 to 2693.0
|
—
|
|
Change in HIV DNA Per 10^6 Cells in Duodenal Tissue Versus PBMC by Drug Regimen Received
Duodenal HIV-DNA
|
-16 copies/10^6 cells
Interval -40.0 to 8.0
|
-846 copies/10^6 cells
Interval -1721.0 to 30.0
|
-325 copies/10^6 cells
Interval -701.0 to 51.0
|
—
|
SECONDARY outcome
Timeframe: nine monthsPopulation: data were not collected due to the samples not being suitable for the epitopes being measured
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: nine monthsPopulation: data were not collected due to inadequate sample volume for this complex experiment design
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and nine monthsPopulation: peripheral CD4 T-cell counts were not measured in the HIV negative cohort
peripheral absolute CD4+ T-cell counts increase from baseline to 9 months of cART by commercial assay
Outcome measures
| Measure |
Maraviroc in Combination With 2 NRTIs
n=10 Participants
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food taken in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Maraviroc PLUS Raltegravir in Combination With 2 NRTIs
n=8 Participants
maraviroc PLUS raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc plus raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food PLUS raltegravir 400mg 1 tablet taken twice a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Efavirenz or Other NNRTI With 2 NRTIs
n=8 Participants
efavirenz or other NNRTI (non-nucleoside reverse transcriptase inhibitor) in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
efavirenz \[or other NNRTI (non-nucleoside reverse transcriptase inhibitor)\]: efavirenz 600mg 1 capsule is taken once a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
HIV Negative Controls Not on ART
HIV-negative
|
|---|---|---|---|---|
|
Changes in CD4+ T-cell Numbers by Treatment Regimen
|
221 cells/mL
Interval 149.0 to 293.0
|
231 cells/mL
Interval 134.0 to 327.0
|
194 cells/mL
Interval 57.0 to 330.0
|
—
|
SECONDARY outcome
Timeframe: nine monthsPopulation: data was not collected/analyzed due to complications in the assays for immune activation in the collected samples
Outcome measures
Outcome data not reported
Adverse Events
Maraviroc in Combination With 2 NRTIs
Maraviroc PLUS Raltegravir in Combination With 2 NRTIs
Efavirenz or Other NNRTI With 2 NRTIs
HIV Negative Controls Not on ART
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Maraviroc in Combination With 2 NRTIs
n=10 participants at risk
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food taken in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Maraviroc PLUS Raltegravir in Combination With 2 NRTIs
n=11 participants at risk
maraviroc PLUS raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
maraviroc plus raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor): maraviroc 300mg 1 tablet taken twice a day without regard to food PLUS raltegravir 400mg 1 tablet taken twice a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
Efavirenz or Other NNRTI With 2 NRTIs
n=11 participants at risk
efavirenz or other NNRTI (non-nucleoside reverse transcriptase inhibitor) in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
efavirenz \[or other NNRTI (non-nucleoside reverse transcriptase inhibitor)\]: efavirenz 600mg 1 capsule is taken once a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
|
HIV Negative Controls Not on ART
n=12 participants at risk
HIV-negative
|
|---|---|---|---|---|
|
Gastrointestinal disorders
gastrointestinal intolerance
|
0.00%
0/10 • during the 9 months of the study participation
|
9.1%
1/11 • during the 9 months of the study participation
|
0.00%
0/11 • during the 9 months of the study participation
|
0.00%
0/12 • during the 9 months of the study participation
|
|
Nervous system disorders
neuropsychiatric side effect
|
0.00%
0/10 • during the 9 months of the study participation
|
0.00%
0/11 • during the 9 months of the study participation
|
9.1%
1/11 • during the 9 months of the study participation
|
0.00%
0/12 • during the 9 months of the study participation
|
Additional Information
David M Asmuth
University of California Davis Medical Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place