Trial Outcomes & Findings for Effect of Addition of Raltegravir (MK-0518) to PI- or NNRTI-Based ART Regimens in HIV Infected Subjects With Undetectable Viral Load (NCT NCT00515827)
NCT ID: NCT00515827
Last Updated: 2021-11-04
Results Overview
HIV-1 RNA level, as measured by single copy assay (units are copies/ml), averaged at weeks 10 and 12. The quantification limit of single copy assay was determined by the volume of plasma tested. When averaging the week 10 and 12 measurements, if one of both measurements were below the single copy assay lower limits, the lower limit of quantification was used to compute the average and the result was treated as below the averaged value.
COMPLETED
PHASE2
53 participants
At Weeks 10 and 12
2021-11-04
Participant Flow
Participant milestones
| Measure |
Raltegravir Then Placebo (Arm A)
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12; halt raltegravir at Week 12 and add placebo twice daily for 12 weeks
|
Placebo Then Raltegravir (Arm B)
Placebo administered twice daily in addition to OBR from entry until Week 12; halt placebo at Week 12 and add 400 mg raltegravir tablet twice daily for 12 weeks.
|
|---|---|---|
|
First Intervention (12 Weeks)
STARTED
|
27
|
26
|
|
First Intervention (12 Weeks)
COMPLETED
|
26
|
25
|
|
First Intervention (12 Weeks)
NOT COMPLETED
|
1
|
1
|
|
Second Intervention (12 Weeks)
STARTED
|
26
|
25
|
|
Second Intervention (12 Weeks)
COMPLETED
|
25
|
25
|
|
Second Intervention (12 Weeks)
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Raltegravir Then Placebo (Arm A)
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12; halt raltegravir at Week 12 and add placebo twice daily for 12 weeks
|
Placebo Then Raltegravir (Arm B)
Placebo administered twice daily in addition to OBR from entry until Week 12; halt placebo at Week 12 and add 400 mg raltegravir tablet twice daily for 12 weeks.
|
|---|---|---|
|
First Intervention (12 Weeks)
Unwilling to adhere to study requirement
|
1
|
1
|
|
Second Intervention (12 Weeks)
Consent withdraw
|
1
|
0
|
Baseline Characteristics
Effect of Addition of Raltegravir (MK-0518) to PI- or NNRTI-Based ART Regimens in HIV Infected Subjects With Undetectable Viral Load
Baseline characteristics by cohort
| Measure |
Raltegravir Then Placebo (Arm A)
n=27 Participants
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12; halt raltegravir at Week 12 and add placebo twice daily for 12 weeks
|
Placebo Then Raltegravir (Arm B)
n=26 Participants
Placebo administered twice daily in addition to OBR from entry until Week 12; halt placebo at Week 12 and add 400 mg raltegravir tablet twice daily for 12 weeks.
|
Total
n=53 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
|
27 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Continuous
|
50 years
STANDARD_DEVIATION 7 • n=5 Participants
|
49 years
STANDARD_DEVIATION 11 • n=7 Participants
|
49 years
STANDARD_DEVIATION 8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
27 participants
n=5 Participants
|
26 participants
n=7 Participants
|
53 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At Weeks 10 and 12Population: 49 subjects who were on study treatment before week 10 and did not experience virologic failure by week 12
HIV-1 RNA level, as measured by single copy assay (units are copies/ml), averaged at weeks 10 and 12. The quantification limit of single copy assay was determined by the volume of plasma tested. When averaging the week 10 and 12 measurements, if one of both measurements were below the single copy assay lower limits, the lower limit of quantification was used to compute the average and the result was treated as below the averaged value.
Outcome measures
| Measure |
Raltegravir (Arm A)
n=25 Participants
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
|
Placebo (Arm B)
n=24 Participants
Placebo administered twice daily in addition to OBR from entry until Week 12
|
|---|---|---|
|
HIV-1 RNA Level
|
1.2 copies/mL
Interval 0.4 to 5.0
|
1.7 copies/mL
Interval 0.5 to 2.3
|
SECONDARY outcome
Timeframe: At pre-entry, entry, weeks 10 and 12Population: All participants who were on study treatment and had not experienced virologic failure
Change in HIV-1 RNA level, as measured by single copy assay (units are copies/ml), from baseline to weeks 10/12 . When averaging the measurements at pre-entry and entry, and at weeks 10 and 12, measurements below the lower limit of quantification (LLQ) were imputed a value of the LLQ divided by 2.
Outcome measures
| Measure |
Raltegravir (Arm A)
n=25 Participants
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
|
Placebo (Arm B)
n=24 Participants
Placebo administered twice daily in addition to OBR from entry until Week 12
|
|---|---|---|
|
Change in HIV-1 RNA Level
|
-0.2 copies/mL
Interval -1.2 to 0.2
|
-0.1 copies/mL
Interval -0.6 to 0.4
|
SECONDARY outcome
Timeframe: At pre-entry, entry, and week 12Population: All participants who were on study treatment and had not experienced virologic failure
CD4 cell counts were assessed by flow cytometry at pre-entry and entry (the baseline value was the average of the two measurements) and at week 12
Outcome measures
| Measure |
Raltegravir (Arm A)
n=23 Participants
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
|
Placebo (Arm B)
n=24 Participants
Placebo administered twice daily in addition to OBR from entry until Week 12
|
|---|---|---|
|
Change in Total CD4 Cell Count
|
42 cells/mm^3
Interval -52.0 to 80.0
|
-44 cells/mm^3
Interval -117.0 to 49.0
|
SECONDARY outcome
Timeframe: At pre-entry, entry, and week 12Population: All participants who were on study treatment and had not experienced virologic failure
CD8 cell counts were assessed by flow cytometry at pre-entry and entry (the baseline value was the average of the two measurements) and at week 12
Outcome measures
| Measure |
Raltegravir (Arm A)
n=23 Participants
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
|
Placebo (Arm B)
n=24 Participants
Placebo administered twice daily in addition to OBR from entry until Week 12
|
|---|---|---|
|
Change in Total CD8 Cell Count
|
55 cells/mm^3
Interval -76.0 to 140.0
|
-39 cells/mm^3
Interval -152.0 to 77.0
|
SECONDARY outcome
Timeframe: At pre-entry, entry, and week 12Population: All participants who were on study treatment and had not experienced virologic failure
Level of CD4+ T-cell activation was determined by measuring the percentage of cells that expressed both the activation marker CD38 and Human leukocyte antigen (HLA)-DR. Levels measured at pre-entry and entry were averaged. Change from baseline to week 12 was defined as CD4+/CD38+/HLA-DR+% at week 12 minus CD4+/CD38+/HLA-DR+% at baseline.
Outcome measures
| Measure |
Raltegravir (Arm A)
n=20 Participants
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
|
Placebo (Arm B)
n=23 Participants
Placebo administered twice daily in addition to OBR from entry until Week 12
|
|---|---|---|
|
Change in CD4+/CD38+/HLA-DR+ Percent
|
-1 % CD4 cells co-express CD38+ and HLA-DR+
Interval -2.0 to 1.0
|
0 % CD4 cells co-express CD38+ and HLA-DR+
Interval -1.0 to 2.0
|
SECONDARY outcome
Timeframe: At pre-entry, entry, and week 12Population: All participants who stayed on study treatment and had not experienced virologic failures.
Level of CD8+ T-cell activation was determined by measuring the percentage of cells that expressed both the activation marker CD38 and Human leukocyte antigen (HLA)-DR. Levels measured at pre-entry and entry were averaged. Change from baseline to week 12 was defined as CD8+/CD38+/HLA-DR+% at week 12 minus CD8+/CD38+/HLA-DR+% at baseline.
Outcome measures
| Measure |
Raltegravir (Arm A)
n=20 Participants
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
|
Placebo (Arm B)
n=23 Participants
Placebo administered twice daily in addition to OBR from entry until Week 12
|
|---|---|---|
|
Change in CD8+/CD38+/HLA-DR+ Percent
|
-1 % CD8 cells co-express CD38+ and HLA-DR+
Interval -2.0 to 2.0
|
0 % CD8 cells co-express CD38+ and HLA-DR+
Interval -2.0 to 5.0
|
SECONDARY outcome
Timeframe: From first day of treatment to week 12Population: All participants on study treatment
Participant who experienced at least one study related grade 2 or higher signs/symptoms, grade 3 or higher laboratory abnormalities and clinical events that are "possibly", "probably" or "definitely" related to study treatment. DAIDS Toxicity Grading Table (2004) was used for grading.
Outcome measures
| Measure |
Raltegravir (Arm A)
n=27 Participants
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
|
Placebo (Arm B)
n=26 Participants
Placebo administered twice daily in addition to OBR from entry until Week 12
|
|---|---|---|
|
Number of Participants Who Experienced Study Related Grade 2 or Higher Signs/Symptoms, Grade 3 or Higher Laboratory Abnormalities and Clinical Events From First Day of Treatment to Week 12
|
2 participants
|
0 participants
|
SECONDARY outcome
Timeframe: From week 12 to week 24Participant who experienced at least one study related grade 2 or higher signs/symptoms, grade 3 or higher laboratory abnormalities and clinical events that are 'possibly', probably', or definitely' related to study treatment. DAIDS Toxicity Grading Table (2004) was used for grading.
Outcome measures
| Measure |
Raltegravir (Arm A)
n=23 Participants
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
|
Placebo (Arm B)
n=25 Participants
Placebo administered twice daily in addition to OBR from entry until Week 12
|
|---|---|---|
|
Number of Participants Who Experienced Study Related Grade 2 or Higher Signs/Symptoms, Grade 3 or Higher Laboratory Abnormalities and Clinical Events From Week 12 to Week 24
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: From first day of treatment to week 12Population: All 53 participants
Participants who discontinued randomized study treatment for any reason
Outcome measures
| Measure |
Raltegravir (Arm A)
n=27 Participants
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
|
Placebo (Arm B)
n=26 Participants
Placebo administered twice daily in addition to OBR from entry until Week 12
|
|---|---|---|
|
Number of Participants Who Discontinued Study Drug
|
4 participants
|
1 participants
|
Adverse Events
Raltegravir
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Raltegravir
n=52 participants at risk
Baseline to Week 12 for Arm A (Raltegravir then Placebo), and Week 12 to Week 24 for Arm B (Placebo then Raltegravir).
|
Placebo
n=52 participants at risk
Week 12 to Week 24 for Arm A (Raltegravir then Placebo), and Baseline to Week 12 for Arm B (Placebo then Raltegravir).
|
|---|---|---|
|
Investigations
Blood BILirubin increased
|
7.7%
4/52 • From study enrollment until study completion
MedDRA 14
|
7.7%
4/52 • From study enrollment until study completion
MedDRA 14
|
|
General disorders
Fatigue
|
0.00%
0/52 • From study enrollment until study completion
MedDRA 14
|
5.8%
3/52 • From study enrollment until study completion
MedDRA 14
|
|
General disorders
Pyrexia
|
3.8%
2/52 • From study enrollment until study completion
MedDRA 14
|
7.7%
4/52 • From study enrollment until study completion
MedDRA 14
|
|
Investigations
Blood bicarbonate abnormal
|
0.00%
0/52 • From study enrollment until study completion
MedDRA 14
|
7.7%
4/52 • From study enrollment until study completion
MedDRA 14
|
|
Investigations
Blood glucose increased
|
7.7%
4/52 • From study enrollment until study completion
MedDRA 14
|
9.6%
5/52 • From study enrollment until study completion
MedDRA 14
|
|
Nervous system disorders
Dizziness
|
5.8%
3/52 • From study enrollment until study completion
MedDRA 14
|
0.00%
0/52 • From study enrollment until study completion
MedDRA 14
|
|
Respiratory, thoracic and mediastinal disorders
dyspnoea
|
1.9%
1/52 • From study enrollment until study completion
MedDRA 14
|
5.8%
3/52 • From study enrollment until study completion
MedDRA 14
|
Additional Information
ACTG ClinicalTrials.gov Coordinator
ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place