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

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

44 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 point

Results posted on

2017-05-30

Participant Flow

Participant milestones

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

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 point

Population: 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

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 months

Population: 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

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 months

Population: 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

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 months

Population: 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 months

Population: 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 months

Population: 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

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 months

Population: 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

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Maraviroc PLUS Raltegravir in Combination With 2 NRTIs

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Efavirenz or Other NNRTI With 2 NRTIs

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

HIV Negative Controls Not on ART

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

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

Phone: (916) 734-8695

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place