Trial Outcomes & Findings for Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure (NCT NCT02263326)
NCT ID: NCT02263326
Last Updated: 2019-10-14
Results Overview
Proportion of participants with treatment failure (defined as virologic failure (HIV RNA \>50 copies/mL), loss to follow-up, or treatment discontinuation) between those who switch to DTG + lamivudine and those who continue their current ART regimen
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
89 participants
Primary outcome timeframe
24 weeks
Results posted on
2019-10-14
Participant Flow
Participant milestones
| Measure |
Dolutegravir Plus Lamivudine
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
|---|---|---|
|
Overall Study
STARTED
|
44
|
45
|
|
Overall Study
COMPLETED
|
43
|
44
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Dolutegravir Plus Lamivudine
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
Baseline Characteristics
Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure
Baseline characteristics by cohort
| Measure |
Dolutegravir Plus Lamivudine
n=44 Participants
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
n=45 Participants
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
Total
n=89 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46 years
n=5 Participants
|
50 years
n=7 Participants
|
47 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
78 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
35 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
19 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
CD4 Cell Count
|
694 cells/mm3
n=5 Participants
|
646 cells/mm3
n=7 Participants
|
680 cells/mm3
n=5 Participants
|
|
Time on Antiretroviral Therapy
|
5.28 years
n=5 Participants
|
6.03 years
n=7 Participants
|
5.7 years
n=5 Participants
|
|
Current ART Regimen
Integrase Inhibitor
|
18 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Current ART Regimen
Protease Inhibitor
|
14 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Current ART Regimen
Nonnucleoside reverse transcriptase inhibitor
|
12 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 weeksProportion of participants with treatment failure (defined as virologic failure (HIV RNA \>50 copies/mL), loss to follow-up, or treatment discontinuation) between those who switch to DTG + lamivudine and those who continue their current ART regimen
Outcome measures
| Measure |
Dolutegravir Plus Lamivudine
n=44 Participants
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
n=45 Participants
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
|---|---|---|
|
Proportion of Participants With Treatment Failure
|
0.0682 proportion of participants
|
0.0667 proportion of participants
|
SECONDARY outcome
Timeframe: 48 weeksProportion of participants with virologic success (\<50 copies/mL) based on FDA snapshot definition
Outcome measures
| Measure |
Dolutegravir Plus Lamivudine
n=44 Participants
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
n=45 Participants
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
|---|---|---|
|
Proportion of Participants With Virologic Success
|
0.9091 proportion of participants
|
0.8889 proportion of participants
|
SECONDARY outcome
Timeframe: Baseline and 48 weeksPopulation: Population with CD4 count data available at baseline and week 48
Change in CD4 count between arms will be presented in the attached statistical analysis table
Outcome measures
| Measure |
Dolutegravir Plus Lamivudine
n=40 Participants
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
n=43 Participants
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
|---|---|---|
|
Change in CD4 Count From Baseline to Week 48
|
39 cells/mm^3
Interval -71.0 to 188.0
|
28 cells/mm^3
Interval -36.0 to 83.0
|
SECONDARY outcome
Timeframe: Baseline and 48 weeksPopulation: Population with total cholesterol data available at baseline and week 48
Change in Total Cholesterol between arms will be presented in the attached statistical analysis table
Outcome measures
| Measure |
Dolutegravir Plus Lamivudine
n=40 Participants
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
n=43 Participants
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
|---|---|---|
|
Change in Total Cholesterol From Baseline to Week 48
|
0 mg/dL
Interval -31.0 to 31.0
|
-1 mg/dL
Interval -13.0 to 9.0
|
SECONDARY outcome
Timeframe: Baseline and Week 48Population: Population with LDL cholesterol data available at baseline and week 48
Change in Low-density lipoprotein (LDL) cholesterol between arms will be presented in the attached statistical analysis table
Outcome measures
| Measure |
Dolutegravir Plus Lamivudine
n=40 Participants
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
n=43 Participants
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
|---|---|---|
|
Change in LDL Cholesterol From Baseline to Week 48
|
2 mg/dL
Interval -19.0 to 27.0
|
-3 mg/dL
Interval -16.0 to 10.0
|
SECONDARY outcome
Timeframe: Baseline and Week 48Population: Population with creatinine clearance data available at baseline and week 48
Change in Creatinine Clearance between arms will be presented in the attached statistical analysis table
Outcome measures
| Measure |
Dolutegravir Plus Lamivudine
n=41 Participants
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
n=43 Participants
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
|---|---|---|
|
Change in Creatinine Clearance From Baseline to Week 48
|
-4 ml/min
Interval -14.0 to 4.0
|
0 ml/min
Interval -6.0 to 5.0
|
SECONDARY outcome
Timeframe: 48 weeksDrug resistance mutations measured by HIV genotyping in patients with confirmed virologic failure
Outcome measures
| Measure |
Dolutegravir Plus Lamivudine
n=44 Participants
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
n=45 Participants
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
|---|---|---|
|
Drug Resistance Associated Mutations
|
0 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 48 weeksPopulation: Participants with HIV-1 single copy assays performed at baseline and week 48 timepoints
Difference in HIV-1 detection by the HIV-1 single copy assay between arms will be presented in statistical analysis
Outcome measures
| Measure |
Dolutegravir Plus Lamivudine
n=36 Participants
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
n=36 Participants
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
|---|---|---|
|
Residual Viremia by HIV-1 Single-copy Assay
|
4.7 copies/mL
Standard Deviation 7.0
|
4.2 copies/mL
Standard Deviation 6.0
|
Adverse Events
Dolutegravir Plus Lamivudine
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Continue Current ART Regimen
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dolutegravir Plus Lamivudine
n=44 participants at risk
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
n=45 participants at risk
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
|---|---|---|
|
Infections and infestations
Grade 4 viral syndrome
|
2.3%
1/44 • Number of events 1 • 48 weeks
After study entry, all laboratory values greater than or equal to Grade 3, any laboratory values that lead to a change in study treatment, and all renal, liver function tests, and lipid values, regardless of grade, were reported. All Grade ≥3 signs/symptoms, any signs/symptoms regardless of grade that lead to a change in treatment, or that meet Expedited Adverse Event (EAE), SAE, or ICH guidelines.
|
0.00%
0/45 • 48 weeks
After study entry, all laboratory values greater than or equal to Grade 3, any laboratory values that lead to a change in study treatment, and all renal, liver function tests, and lipid values, regardless of grade, were reported. All Grade ≥3 signs/symptoms, any signs/symptoms regardless of grade that lead to a change in treatment, or that meet Expedited Adverse Event (EAE), SAE, or ICH guidelines.
|
|
Cardiac disorders
Grade 4 myocardial infarctions
|
0.00%
0/44 • 48 weeks
After study entry, all laboratory values greater than or equal to Grade 3, any laboratory values that lead to a change in study treatment, and all renal, liver function tests, and lipid values, regardless of grade, were reported. All Grade ≥3 signs/symptoms, any signs/symptoms regardless of grade that lead to a change in treatment, or that meet Expedited Adverse Event (EAE), SAE, or ICH guidelines.
|
4.4%
2/45 • Number of events 2 • 48 weeks
After study entry, all laboratory values greater than or equal to Grade 3, any laboratory values that lead to a change in study treatment, and all renal, liver function tests, and lipid values, regardless of grade, were reported. All Grade ≥3 signs/symptoms, any signs/symptoms regardless of grade that lead to a change in treatment, or that meet Expedited Adverse Event (EAE), SAE, or ICH guidelines.
|
Other adverse events
| Measure |
Dolutegravir Plus Lamivudine
n=44 participants at risk
dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks
lamivudine: 300 mg tablet by mouth once daily for 48 weeks
|
Continue Current ART Regimen
n=45 participants at risk
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
|
|---|---|---|
|
Hepatobiliary disorders
Grade 3 bilirubinemia
|
0.00%
0/44 • 48 weeks
After study entry, all laboratory values greater than or equal to Grade 3, any laboratory values that lead to a change in study treatment, and all renal, liver function tests, and lipid values, regardless of grade, were reported. All Grade ≥3 signs/symptoms, any signs/symptoms regardless of grade that lead to a change in treatment, or that meet Expedited Adverse Event (EAE), SAE, or ICH guidelines.
|
6.7%
3/45 • Number of events 3 • 48 weeks
After study entry, all laboratory values greater than or equal to Grade 3, any laboratory values that lead to a change in study treatment, and all renal, liver function tests, and lipid values, regardless of grade, were reported. All Grade ≥3 signs/symptoms, any signs/symptoms regardless of grade that lead to a change in treatment, or that meet Expedited Adverse Event (EAE), SAE, or ICH guidelines.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place