Trial Outcomes & Findings for Study Assessing Dolutegravir in HIV-1 Infected Subjects With Virus Resistant to Raltegravir and/or Elivitegravir (NCT NCT01568892)

Last Updated: 2018-07-02

Results Overview

Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1) and Day 8. Change from Baseline was calculated as the value at Day 8 minus the value at Baseline (Day 1). The analysis was performed using statistical modeling correcting for Baseline plasma HIV-1 RNA, Baseline Dolutegravir (DTG) fold change (FC), the overall susceptibility score (OSS) of the failing regimen, and the interaction between DTG FC and treatment. Means and differences were calculated using the average Baseline DTG FC of the entire Intent-to-Treat Exposed (ITT-E) Population. The last observation carried forward with discontinuation equals Baseline (LOCFDB) dataset was used for the analysis. For the LOCFDB dataset, missing values were carried forward from the previous, non-missing, available on-treatment assessment, except formissing values due to premature withdrawal or Day 8 missing values, which had the Baseline value imputed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

30 participants

Primary outcome timeframe

Baseline and Day 8

Results posted on

2018-07-02

Participant Flow

Participants (par.) meeting eligibility criteria at screening entered a 7-day randomized, double-blind, placebo-controlled phase. At Day 8, all par. entered an open-label phase and continued to receive dolutegravir with an optimized background regimen. A total of 75 par. were screened; 45 par. were screen failures, and 30 par. were randomized.

Participant milestones

Participant milestones
Measure	DTG 50 mg BID Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Double-blind Phase STARTED	14	16
Double-blind Phase COMPLETED	14	16
Double-blind Phase NOT COMPLETED	0	0
Open-label Phase STARTED	13	16
Open-label Phase COMPLETED	7	13
Open-label Phase NOT COMPLETED	6	3

Reasons for withdrawal

Reasons for withdrawal
Measure	DTG 50 mg BID Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Open-label Phase Adverse Event	2	0
Open-label Phase Lack of Efficacy	4	2
Open-label Phase Lost to Follow-up	0	1

Baseline Characteristics

Study Assessing Dolutegravir in HIV-1 Infected Subjects With Virus Resistant to Raltegravir and/or Elivitegravir

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Total n=30 Participants Total of all reporting groups
Age, Continuous	47.5 Years STANDARD_DEVIATION 11.56 • n=5 Participants	48.6 Years STANDARD_DEVIATION 8.85 • n=7 Participants	48.1 Years STANDARD_DEVIATION 10.04 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Missing: None of the Available Races Applied	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 8

Population: ITT-E Population: all randomized participants who received at least one dose of study medication. One participant receiving DTG 50 mg BID was excluded from analysis because they had no Baseline DTG FC value.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=13 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Mean Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at Day 8	-1.06 Log 10 copies per milliliter (c/mL) Standard Error 0.168	0.10 Log 10 copies per milliliter (c/mL) Standard Error 0.183

SECONDARY outcome

Timeframe: Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84

Population: ITT-E Population. The Observed Case dataset, in which only the data that are available at a particular time point are used, with no imputation for missing values, was used for analysis. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Day 8, Day 28, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, and Week 84. NA indicates data was not available.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Absolute Values in Plasma HIV-1 RNA Over Time Baseline, n=14, 16	4.02 Log10 c/mL Standard Deviation 0.940	4.42 Log10 c/mL Standard Deviation 0.760
Absolute Values in Plasma HIV-1 RNA Over Time Day 8, n=14, 16	2.95 Log10 c/mL Standard Deviation 0.790	4.39 Log10 c/mL Standard Deviation 0.844
Absolute Values in Plasma HIV-1 RNA Over Time Day 28, n=13, 16	2.14 Log10 c/mL Standard Deviation 0.772	2.30 Log10 c/mL Standard Deviation 1.054
Absolute Values in Plasma HIV-1 RNA Over Time Week 8, n=11, 16	2.35 Log10 c/mL Standard Deviation 0.851	2.10 Log10 c/mL Standard Deviation 0.913
Absolute Values in Plasma HIV-1 RNA Over Time Week 12, n=12, 14	2.51 Log10 c/mL Standard Deviation 1.048	2.27 Log10 c/mL Standard Deviation 1.179
Absolute Values in Plasma HIV-1 RNA Over Time Week 16, n=12, 16	2.57 Log10 c/mL Standard Deviation 1.093	2.18 Log10 c/mL Standard Deviation 1.098
Absolute Values in Plasma HIV-1 RNA Over Time Week 24, n=11, 15	2.65 Log10 c/mL Standard Deviation 1.219	1.88 Log10 c/mL Standard Deviation 0.654
Absolute Values in Plasma HIV-1 RNA Over Time Week 32, n=11, 14	2.72 Log10 c/mL Standard Deviation 1.176	1.81 Log10 c/mL Standard Deviation 0.664
Absolute Values in Plasma HIV-1 RNA Over Time Week 40, n=7, 12	2.35 Log10 c/mL Standard Deviation 1.169	1.68 Log10 c/mL Standard Deviation 0.133
Absolute Values in Plasma HIV-1 RNA Over Time Week 48, n=8, 13	2.47 Log10 c/mL Standard Deviation 1.037	1.62 Log10 c/mL Standard Deviation 0.088
Absolute Values in Plasma HIV-1 RNA Over Time Week 60, n=5, 12	2.15 Log10 c/mL Standard Deviation 1.013	1.67 Log10 c/mL Standard Deviation 0.150
Absolute Values in Plasma HIV-1 RNA Over Time Week 72, n=3, 4	2.35 Log10 c/mL Standard Deviation 1.312	1.62 Log10 c/mL Standard Deviation 0.054
Absolute Values in Plasma HIV-1 RNA Over Time Week 84, n=0, 1	—	1.59 Log10 c/mL Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.

SECONDARY outcome

Timeframe: Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84

Population: ITT-E Population. The Observed Case dataset, in which only the data that are available at the particular time point are used, with no imputation for missing values, was used for analysis. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Week 48, n=8, 13	-1.34 Log10 c/mL Standard Deviation 1.235	-2.77 Log10 c/mL Standard Deviation 0.881
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Week 60, n=5, 12	-1.91 Log10 c/mL Standard Deviation 1.400	-2.71 Log10 c/mL Standard Deviation 0.863
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Week 72, n=3, 4	-2.08 Log10 c/mL Standard Deviation 1.311	-3.31 Log10 c/mL Standard Deviation 0.968
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Week 24, n=11, 15	-1.38 Log10 c/mL Standard Deviation 1.151	-2.53 Log10 c/mL Standard Deviation 1.033
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Day 8, n=14, 16	-1.07 Log10 c/mL Standard Deviation 0.683	-0.03 Log10 c/mL Standard Deviation 0.262
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Day 28, n=13, 16	-1.87 Log10 c/mL Standard Deviation 0.898	-2.12 Log10 c/mL Standard Deviation 1.111
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Week 8, n=11, 16	-1.89 Log10 c/mL Standard Deviation 0.890	-2.32 Log10 c/mL Standard Deviation 1.112
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Week 12, n=12, 14	-1.54 Log10 c/mL Standard Deviation 1.022	-2.02 Log10 c/mL Standard Deviation 1.245
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Week 16, n=12, 16	-1.48 Log10 c/mL Standard Deviation 1.101	-2.24 Log10 c/mL Standard Deviation 1.180
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Week 32, n=11, 14	-1.31 Log10 c/mL Standard Deviation 1.059	-2.62 Log10 c/mL Standard Deviation 0.931
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Week 40, n=7, 12	-1.48 Log10 c/mL Standard Deviation 1.445	-2.70 Log10 c/mL Standard Deviation 0.843
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Baseline, n=14, 16	4.02 Log10 c/mL Standard Deviation 0.940	4.42 Log10 c/mL Standard Deviation 0.760
Mean Change From Baseline in Plasma HIV-1 RNA Over Time Week 84, n=0, 1	—	-3.75 Log10 c/mL Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.

SECONDARY outcome

Timeframe: Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40 and 48

Population: ITT-E Population. The Snapshot dataset was used for analysis.

Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1); Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, and 48. Number of participants with plasma HIV-1 RNA level \<50 c/mL was obtained using Food and Drug Administration's (FDA's) snapshot algorithm, where all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) were treated as non-responders. Also, participants who switched their concomitant antiretroviral therapy (ART) prior to the visit of interest as follows were also treated as non-responders: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol; however, the decision to switch is not documented as being before or at the first On-treatment visit after switching to optimized background regimen (OBR) (i.e. Day 28) where HIV-1 RNA is assessed.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time Baseline	0 Participants	0 Participants
Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time Day 8	1 Participants	0 Participants
Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time Day 28	6 Participants	6 Participants
Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time Week 8	5 Participants	9 Participants
Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time Week 12	6 Participants	8 Participants
Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time Week 16	5 Participants	8 Participants
Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time Week 24	6 Participants	8 Participants
Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time Week 32	4 Participants	9 Participants
Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time Week 40	4 Participants	7 Participants
Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time Week 48	3 Participants	9 Participants

SECONDARY outcome

Timeframe: Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40 and 48

Population: ITT-E Population. The Snapshot dataset was used for analysis.

Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1); Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40 and 48. Number of participants with plasma HIV-1 RNA level \<400 c/mL was obtained using FDA's snapshot algorithm, where all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) were treated as non-responders. Also, participants who switch their concomitant ART prior to the visit of interest as follows were also treated as non-responders: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol; however the decision to switch is not documented as being before or at the first On-treatment visit after switching to OBR (i.e. Day 28) where HIV-1 RNA is assessed.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time Baseline	2 Participants	0 Participants
Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time Day 8	4 Participants	0 Participants
Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time Day 28	9 Participants	12 Participants
Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time Week 8	7 Participants	13 Participants
Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time Week 12	7 Participants	10 Participants
Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time Week 16	7 Participants	12 Participants
Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time Week 24	6 Participants	11 Participants
Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time Week 32	6 Participants	10 Participants
Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time Week 40	5 Participants	10 Participants
Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time Week 48	6 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84

Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Baseline, n=14, 16	163.5 Cells per cubic millimeters Interval 111.0 to 231.0	90.5 Cells per cubic millimeters Interval 46.0 to 267.5
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Day 8, n=14, 15	198.5 Cells per cubic millimeters Interval 154.0 to 239.0	102.0 Cells per cubic millimeters Interval 50.0 to 310.0
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Day 28, n=13, 16	174.0 Cells per cubic millimeters Interval 168.0 to 335.0	234.0 Cells per cubic millimeters Interval 114.5 to 303.5
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Week 8, n=11, 16	211.0 Cells per cubic millimeters Interval 71.0 to 401.0	228.0 Cells per cubic millimeters Interval 124.0 to 357.5
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Week 12, n=12, 14	223.5 Cells per cubic millimeters Interval 115.0 to 345.5	217.5 Cells per cubic millimeters Interval 121.0 to 333.0
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Week 16, n=12, 16	241.0 Cells per cubic millimeters Interval 107.5 to 382.5	262.5 Cells per cubic millimeters Interval 132.5 to 436.5
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Week 24, n=11, 15	232.0 Cells per cubic millimeters Interval 116.0 to 509.0	242.0 Cells per cubic millimeters Interval 194.0 to 399.0
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Week 32, n=11, 14	213.0 Cells per cubic millimeters Interval 91.0 to 489.0	326.0 Cells per cubic millimeters Interval 229.0 to 542.0
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Week 40, n=8, 12	299.5 Cells per cubic millimeters Interval 212.5 to 566.5	328.0 Cells per cubic millimeters Interval 204.5 to 508.0
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Week 48, n=8, 13	328.0 Cells per cubic millimeters Interval 263.0 to 526.5	370.0 Cells per cubic millimeters Interval 231.0 to 457.0
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Week 60, n=5, 12	321.0 Cells per cubic millimeters Interval 234.0 to 328.0	333.0 Cells per cubic millimeters Interval 217.5 to 541.0
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Week 72, n=3, 4	321.0 Cells per cubic millimeters Interval 261.0 to 465.0	299.5 Cells per cubic millimeters Interval 231.5 to 349.0
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time Week 84, n=0, 1	—	368.0 Cells per cubic millimeters Interval 368.0 to 368.0

SECONDARY outcome

Timeframe: Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84

Population: ITT-E Population. Observed dataset was used for analysis. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Median Change From Baseline in CD4+ Cell Counts Over Time Baseline, n=14, 16	163.5 Cells per cubic millimeters Interval 111.0 to 231.0	90.5 Cells per cubic millimeters Interval 46.0 to 267.5
Median Change From Baseline in CD4+ Cell Counts Over Time Day 8, n=14, 15	7.0 Cells per cubic millimeters Interval 0.0 to 94.0	0.0 Cells per cubic millimeters Interval -12.0 to 24.0
Median Change From Baseline in CD4+ Cell Counts Over Time Day 28, n=13, 16	14.0 Cells per cubic millimeters Interval 6.0 to 68.0	68.5 Cells per cubic millimeters Interval 5.0 to 140.5
Median Change From Baseline in CD4+ Cell Counts Over Time Week 8, n=11, 16	34.0 Cells per cubic millimeters Interval 10.0 to 96.0	87.5 Cells per cubic millimeters Interval 9.5 to 138.5
Median Change From Baseline in CD4+ Cell Counts Over Time Week 12, n=12, 14	49.0 Cells per cubic millimeters Interval -5.0 to 83.0	79.0 Cells per cubic millimeters Interval 1.0 to 121.0
Median Change From Baseline in CD4+ Cell Counts Over Time Week 16, n=12, 16	76.5 Cells per cubic millimeters Interval 3.0 to 151.0	70.0 Cells per cubic millimeters Interval 20.5 to 235.0
Median Change From Baseline in CD4+ Cell Counts Over Time Week 24, n=11, 15	39.0 Cells per cubic millimeters Interval 0.0 to 134.0	117.0 Cells per cubic millimeters Interval 23.0 to 163.0
Median Change From Baseline in CD4+ Cell Counts Over Time Week 32, n=11, 14	48.0 Cells per cubic millimeters Interval 0.0 to 198.0	135.5 Cells per cubic millimeters Interval 58.0 to 271.0
Median Change From Baseline in CD4+ Cell Counts Over Time Week 40, n=8, 12	90.5 Cells per cubic millimeters Interval 45.0 to 226.5	125.5 Cells per cubic millimeters Interval 50.0 to 244.5
Median Change From Baseline in CD4+ Cell Counts Over Time Week 48, n=8, 13	115.0 Cells per cubic millimeters Interval 96.0 to 226.5	156.0 Cells per cubic millimeters Interval 68.0 to 293.0
Median Change From Baseline in CD4+ Cell Counts Over Time Week 60, n=5, 12	170.0 Cells per cubic millimeters Interval 65.0 to 210.0	146.0 Cells per cubic millimeters Interval 73.5 to 242.0
Median Change From Baseline in CD4+ Cell Counts Over Time Week 72, n=3, 4	163.0 Cells per cubic millimeters Interval 96.0 to 354.0	174.0 Cells per cubic millimeters Interval 147.0 to 225.0
Median Change From Baseline in CD4+ Cell Counts Over Time Week 84, n=0, 1	—	269.0 Cells per cubic millimeters Interval 269.0 to 269.0

SECONDARY outcome

Timeframe: Baseline; Day 28; Weeks 12, 24, and 48

Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline; Day 28; and Weeks 12, 24, and 48.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Absolute Values in Cluster of Differentiation 8+ (CD8+) Cell Counts Over Time Baseline, n=14, 16	896.0 Cells per cubic millimeter Interval 589.0 to 1689.0	808.5 Cells per cubic millimeter Interval 436.5 to 1221.0
Absolute Values in Cluster of Differentiation 8+ (CD8+) Cell Counts Over Time Day 28, n=13, 16	1135.0 Cells per cubic millimeter Interval 598.0 to 1741.0	973.0 Cells per cubic millimeter Interval 675.0 to 1322.0
Absolute Values in Cluster of Differentiation 8+ (CD8+) Cell Counts Over Time Week 12, n=11, 14	1198.0 Cells per cubic millimeter Interval 591.0 to 1977.0	1184.0 Cells per cubic millimeter Interval 860.0 to 1711.0
Absolute Values in Cluster of Differentiation 8+ (CD8+) Cell Counts Over Time Week 24, n=11, 15	1160.0 Cells per cubic millimeter Interval 526.0 to 1908.0	1323.0 Cells per cubic millimeter Interval 969.0 to 1622.0
Absolute Values in Cluster of Differentiation 8+ (CD8+) Cell Counts Over Time Week 48, n=6, 12	1295.0 Cells per cubic millimeter Interval 837.0 to 1818.0	1147.0 Cells per cubic millimeter Interval 753.0 to 1570.0

SECONDARY outcome

Timeframe: Baseline; Day 28; Weeks 12, 24, and 48

Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline; Day 28; and Weeks 12, 24, and 48. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Median Change From Baseline in CD8+ Cell Counts Over Time Day 28, n=13, 16	227.0 Cells per cubic millimeter Interval -135.0 to 301.0	177.0 Cells per cubic millimeter Interval 51.0 to 278.5
Median Change From Baseline in CD8+ Cell Counts Over Time Baseline, n=14, 16	896.0 Cells per cubic millimeter Interval 589.0 to 1689.0	808.5 Cells per cubic millimeter Interval 436.5 to 1221.0
Median Change From Baseline in CD8+ Cell Counts Over Time Week 12, n=11, 14	151.0 Cells per cubic millimeter Interval -150.0 to 379.0	288.0 Cells per cubic millimeter Interval 193.0 to 484.0
Median Change From Baseline in CD8+ Cell Counts Over Time Week 24, n=11, 15	79.0 Cells per cubic millimeter Interval -183.0 to 269.0	543.0 Cells per cubic millimeter Interval 35.0 to 930.0
Median Change From Baseline in CD8+ Cell Counts Over Time Week 48, n=6, 12	88.0 Cells per cubic millimeter Interval -19.0 to 179.0	124.0 Cells per cubic millimeter Interval -102.5 to 238.5

SECONDARY outcome

Timeframe: From the day of the first dose of study drug until early withdrawal or the Week 48 analysis cut-off date (median of 55 study weeks)

Population: ITT-E Population

The number of participants with HIV-1 disease progression (AIDS or death) was assessed per the Centers for Disease Control and Prevention (CDC) 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. The CDC classifies HIV infection as Category A (participants with asymptomatic HIV infection, acute HIV infection with accompanying illness, or persistent generalized lymphadenopathy), Category B (participants with symptomatic non-AIDS condition, i.e., conditions that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection), and Category C (includes AIDS indicator conditions as defined by diagnostic or presumptive measures).

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Number of Participants With the Indicated Type of HIV-1 Disease Progression (Acquired Immunodeficiency Syndrome [AIDS] or Death [DT]) From CDC Class A to CDC Class C	0 Participants	0 Participants
Number of Participants With the Indicated Type of HIV-1 Disease Progression (Acquired Immunodeficiency Syndrome [AIDS] or Death [DT]) From CDC Class B to CDC Class C	0 Participants	0 Participants
Number of Participants With the Indicated Type of HIV-1 Disease Progression (Acquired Immunodeficiency Syndrome [AIDS] or Death [DT]) From CDC Class C to new CDC Class C	0 Participants	0 Participants
Number of Participants With the Indicated Type of HIV-1 Disease Progression (Acquired Immunodeficiency Syndrome [AIDS] or Death [DT]) From CDC Class A, B, or C to Death	2 Participants	0 Participants

SECONDARY outcome

Timeframe: From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks)

Population: Safety Population: all randomized participants who received at least one dose of study medication

An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity; or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in other situations. Adverse events were graded for severity according to the Division of AIDS (DAIDS) toxicity scales as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (potentially life threatening).

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Number of Participants With Any Adverse Event (Serious and Non-serious) of the Indicated Grade Grade 1	0 Participants	4 Participants
Number of Participants With Any Adverse Event (Serious and Non-serious) of the Indicated Grade Grade 2	7 Participants	6 Participants
Number of Participants With Any Adverse Event (Serious and Non-serious) of the Indicated Grade Grade 3	2 Participants	3 Participants
Number of Participants With Any Adverse Event (Serious and Non-serious) of the Indicated Grade Grade 4	2 Participants	1 Participants

SECONDARY outcome

Timeframe: From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks)

Population: Safety Population

Participants with post-Baseline-emergent clinical chemistry toxicities were analyzed. Clinical chemistry toxicities were graded for severity according to the DAIDS toxicity scales as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (potentially life threatening).

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade Grade 1	5 Participants	4 Participants
Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade Grade 2	5 Participants	5 Participants
Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade Grade 3	0 Participants	4 Participants
Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade Grade 4	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks)

Population: Safety Population

Participants with post-Baseline-emergent hematology toxicities were analyzed. Hematology toxicities were graded for severity according to the DAIDS toxicity scales as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (potentially life threatening).

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade Grade 1	2 Participants	3 Participants
Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade Grade 2	2 Participants	5 Participants
Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade Grade 3	0 Participants	1 Participants
Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade Grade 4	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 8, Day 28, and Week 24

Population: PK concentration Population comprised of all participants who received DTG, underwent PK sampling during the study, and provided evaluable DTG plasma concentration data.

The area under the time concentration curve over the dosing interval (AUC\[0-tau\]) of DTG was assessed by a population pharmacokinetic (PK) modeling approach using pooled DTG PK data from multiple studies. Blood samples for the determination of plasma DTG concentration were collected at the following time points: pre-dose and 1-3 hours post-dose on Day 8; pre-dose and within a post-dose window (1-3 hours or 4-12 hours) on Day 28 and Week 24. For Day 8 PK, only samples collected from participants randomized to the active DTG arm were analyzed.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=29 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
AUC(0-tau) of DTG	37.9 µghour per mL (µghr/mL) Geometric Coefficient of Variation 41.8	—

SECONDARY outcome

Timeframe: Day 8, Day 28, and Week 24

Population: PK concentration Population comprised of all participants who received DTG, underwent PK sampling during the study, and provided evaluable DTG plasma concentration data.

The maximal concentration (Cmax) of DTG was assessed by a population PK modeling approach using pooled DTG PK data from multiple studies. Blood samples for the determination of plasma DTG concentration were collected at the following time points: pre-dose and 1-3 hours post-dose on Day 8; pre-dose and within a post-dose window (1-3 hours or 4-12 hours) on Day 28 and Week 24. For Day 8 PK, only samples collected from participants randomized to the active DTG arm were analyzed.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=29 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Cmax of DTG	4.14 Micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 32.6	—

SECONDARY outcome

Timeframe: Day 8, Day 28, and Week 24

Population: PK Parameter Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Parameter Population.

Blood samples for the determination of plasma DTG pre-dose concentration were collected pre-dose on Day 8, Day 28, and Week 24. For Day 8 PK, only samples collected from participants randomized to the active DTG arm were analyzed. C0 Avg was calculated at Week 24 as the mean of the concentration at Day 8, Day 28, and Week 24.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=13 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Plasma DTG Pre-dose Concentration (C0) at Day 8, Day 28, and Week 24; and Average DTG C0 (C0 Avg) at Week 24 C0_avg, n=13, 16	1.820 µg/mL Geometric Coefficient of Variation 188	2.307 µg/mL Geometric Coefficient of Variation 76
Plasma DTG Pre-dose Concentration (C0) at Day 8, Day 28, and Week 24; and Average DTG C0 (C0 Avg) at Week 24 Day 8 C0, n=10, 0	3.043 µg/mL Geometric Coefficient of Variation 44	—
Plasma DTG Pre-dose Concentration (C0) at Day 8, Day 28, and Week 24; and Average DTG C0 (C0 Avg) at Week 24 Day 28 C0, n=11, 16	1.393 µg/mL Geometric Coefficient of Variation 189	2.154 µg/mL Geometric Coefficient of Variation 81
Plasma DTG Pre-dose Concentration (C0) at Day 8, Day 28, and Week 24; and Average DTG C0 (C0 Avg) at Week 24 Week 24 C0, n=10, 14	1.864 µg/mL Geometric Coefficient of Variation 110	2.201 µg/mL Geometric Coefficient of Variation 145

SECONDARY outcome

Timeframe: From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks)

Population: PDVF Genotypic/Phenotypic Population: all participants in the ITT-E population with protocol-defined virologic failure. Only participants with Baseline integrase mutations with PDVF who had paired Baseline and time of PDVF samples were considered for analysis.

For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of \<1 log10 copies/mL by Day 28, with subsequent confirmation, unless plasma HIV-1 RNA is \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>=400 copies/mL on or after Week 24 or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to \>=400 copies/mL after prior confirmed suppression to \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>1 log10 copies/mL above the nadir value, where nadir is \>=400 copies/mL.Treatment-emergent IN mutations are those detected at the time of PDVF but not at Baseline.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=5 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=2 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance Any integrase mutation	4 Participants	1 Participants
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance L74L/M	1 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance T97A	2 Participants	1 Participants
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance E138E/K	1 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance E138K	1 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance S147G	1 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance N155N/H	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks)

For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. The FC in IC50 (50% inhibitory concentration) for DTG relative to wild-type virus was determined for virus isolated at Baseline and at the time of PDVF. The number of participants with the indicated change (ratio) in the two values at the time of PDVF is presented. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of \<1 log10 copies/mL by Day 28, with subsequent confirmation, unless plasma HIV-1 RNA is \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>=400 copies/mL on or after Week 24 or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to \>=400 copies/mL after prior confirmed suppression to \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>1 log10 copies/mL above the nadir value, where nadir is \>=400 copies/mL.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=5 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=2 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Number of Participants With the Indicated Fold Increase in Fold Change (FC) in the 50% Inhibitory Concentration Relative to Wild-type Virus for DTG (i.e. PDVF FC/Baseline FC Ratio) at the Time of PDVF, as a Measure of Phenotypic Resistance 4-<8 fold increase in DTG FC	0 Participants	1 Participants
Number of Participants With the Indicated Fold Increase in Fold Change (FC) in the 50% Inhibitory Concentration Relative to Wild-type Virus for DTG (i.e. PDVF FC/Baseline FC Ratio) at the Time of PDVF, as a Measure of Phenotypic Resistance >=8 fold increase in DTG FC	4 Participants	0 Participants

SECONDARY outcome

Timeframe: From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks)

Population: Safety Population

The number of participants who permanently discontinued study treatment due to AEs is presented.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Number of Participants Who Discontinued Study Treatment Due to AEs	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: Safety Population. Only those participants with data available at the specified time point was analyzed.

Twelve lead ECG was performed using an automated ECG machine. The number of participants with abnormal-clinically significant ECG findings at any time on-treatment is reported.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=12 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=15 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 24 and 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

Vital signs including SBP and DBP were measured at Baseline, Week 24 and Week 48. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP; Baseline; n=14, 16	120.4 millimeters of mercury Standard Deviation 15.60	113.4 millimeters of mercury Standard Deviation 9.99
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP; Week 24; n=11, 15	2.0 millimeters of mercury Standard Deviation 12.28	2.8 millimeters of mercury Standard Deviation 13.82
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP; Week 48; n=6, 12	-0.7 millimeters of mercury Standard Deviation 19.50	3.1 millimeters of mercury Standard Deviation 12.57
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP; Baseline; n=14, 16	78.9 millimeters of mercury Standard Deviation 12.51	75.1 millimeters of mercury Standard Deviation 8.46
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP; Week 24; n=11, 15	-0.5 millimeters of mercury Standard Deviation 9.49	-1.2 millimeters of mercury Standard Deviation 10.35
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP; Week 48; n=6, 12	-1.2 millimeters of mercury Standard Deviation 13.92	-3.2 millimeters of mercury Standard Deviation 8.78

SECONDARY outcome

Timeframe: Baseline and Weeks 24 and 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

Vital signs including heart rate was measured at Baseline, Week 24 and Week 48. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Change From Baseline in Heart Rate Baseline; n=14, 16	72.5 beats per minute Standard Deviation 9.70	75.9 beats per minute Standard Deviation 14.56
Change From Baseline in Heart Rate Week 24; n=11, 15	-1.4 beats per minute Standard Deviation 8.42	0.7 beats per minute Standard Deviation 11.20
Change From Baseline in Heart Rate Week 48; 6, 12	2.2 beats per minute Standard Deviation 11.03	-2.5 beats per minute Standard Deviation 17.76

SECONDARY outcome

Timeframe: Baseline, Week 24 and 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

Blood samples were collected for the analysis of clinical chemistry parameters such as albumin. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Change From Baseline in Albumin Level Albumin; Baseline; n=14, 16	43.1 grams per liter Standard Deviation 4.13	43.4 grams per liter Standard Deviation 3.88
Change From Baseline in Albumin Level Albumin; Week 24; n=11, 15	0.0 grams per liter Standard Deviation 3.66	0.0 grams per liter Standard Deviation 3.87
Change From Baseline in Albumin Level Albumin; Week 48; n=8, 13	1.3 grams per liter Standard Deviation 2.55	-0.8 grams per liter Standard Deviation 3.69

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

Blood samples were collected for the analysis of clinical chemistry parameters such as ALP, ALT, AST and creatine kinase. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles)

Blood samples were collected for the analysis of clinical chemistry parameters such as T. Bil and creatinine. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Population: Safety Population. Lipid and glucose parameters were only summarized on fasting data. Only those participants available at the specified time points were analyzed (represented by n=X in category titles)

Blood samples were collected for the analysis of clinical chemistry parameters such as cholesterol, chloride, CO2/HCO3, glucose, high density lipoprotein (HDL) cholesterol, potassium, LDL cholesterol, sodium, phosphorus inorganic, triglycerides and urea/blood urea nitrogen (BUN). Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 28, Week 8, Week 16, Week 24, Week 32 and Week 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles)

Creatinine clearance was calculated using Cockcroft-Gault formula. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Change From Baseline in Creatinine Clearance Baseline; n=14, 16	106.8 Milliliters per minute Standard Deviation 31.79	104.8 Milliliters per minute Standard Deviation 36.96
Change From Baseline in Creatinine Clearance Day 8; n=1, 0	-13.0 Milliliters per minute Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.	—
Change From Baseline in Creatinine Clearance Day 28; n=13, 16	-10.5 Milliliters per minute Standard Deviation 13.06	-10.4 Milliliters per minute Standard Deviation 13.06
Change From Baseline in Creatinine Clearance Week 8; n=0, 1	—	-12.0 Milliliters per minute Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.
Change From Baseline in Creatinine Clearance Week 16; n=10, 15	-7.3 Milliliters per minute Standard Deviation 12.00	-12.5 Milliliters per minute Standard Deviation 16.41
Change From Baseline in Creatinine Clearance Week 24; n=11, 15	-2.3 Milliliters per minute Standard Deviation 13.94	-13.9 Milliliters per minute Standard Deviation 17.38
Change From Baseline in Creatinine Clearance Week 32; n=9, 14	-1.4 Milliliters per minute Standard Deviation 8.82	-16.0 Milliliters per minute Standard Deviation 16.31
Change From Baseline in Creatinine Clearance Week 48; n=6, 12	-6.8 Milliliters per minute Standard Deviation 17.61	-16.5 Milliliters per minute Standard Deviation 14.34

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

Blood samples were collected for the analysis of clinical chemistry parameters such as lipase level. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Change From Baseline in Lipase Levels Lipase; Baseline; n=14, 16	29.1 Units per liter Standard Deviation 12.37	34.0 Units per liter Standard Deviation 18.54
Change From Baseline in Lipase Levels Lipase; Day 8; n=14, 15	3.4 Units per liter Standard Deviation 9.19	12.5 Units per liter Standard Deviation 32.97
Change From Baseline in Lipase Levels Lipase; Day 28; n=13, 16	3.3 Units per liter Standard Deviation 9.18	17.7 Units per liter Standard Deviation 63.64
Change From Baseline in Lipase Levels Lipase; Week 8; n=11, 16	2.6 Units per liter Standard Deviation 8.65	13.6 Units per liter Standard Deviation 42.89
Change From Baseline in Lipase Levels Lipase; Week 12; n=11, 14	-2.4 Units per liter Standard Deviation 8.91	3.0 Units per liter Standard Deviation 19.24
Change From Baseline in Lipase Levels Lipase; Week 16; n=10, 16	7.6 Units per liter Standard Deviation 13.94	-0.8 Units per liter Standard Deviation 12.90
Change From Baseline in Lipase Levels Lipase; Week 24; n=11, 15	-2.7 Units per liter Standard Deviation 9.91	10.5 Units per liter Standard Deviation 29.18
Change From Baseline in Lipase Levels Lipase; Week 32; n=11, 14	0.8 Units per liter Standard Deviation 9.82	20.6 Units per liter Standard Deviation 49.70
Change From Baseline in Lipase Levels Lipase; Week 40; n=8, 12	0.6 Units per liter Standard Deviation 8.53	5.6 Units per liter Standard Deviation 19.78
Change From Baseline in Lipase Levels Lipase; Week 48; n=8, 13	3.8 Units per liter Standard Deviation 6.18	3.4 Units per liter Standard Deviation 16.05
Change From Baseline in Lipase Levels Lipase; Week 60; n=5, 12	5.0 Units per liter Standard Deviation 8.40	5.9 Units per liter Standard Deviation 22.01
Change From Baseline in Lipase Levels Lipase; Week 72; n=3, 4	16.0 Units per liter Standard Deviation 14.11	41.0 Units per liter Standard Deviation 94.20
Change From Baseline in Lipase Levels Lipase; Week 84; n=0, 1	—	-9.0 Units per liter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles)

Blood samples were collected for the analysis of hematology parameters such as basophils, eosinophils. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

Blood samples were collected for the analysis of hematology parameters such as hemoglobin. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Change From Baseline in Hemoglobin Level Baseline; n=14, 16	132.9 Grams per liter Standard Deviation 16.16	129.9 Grams per liter Standard Deviation 21.08
Change From Baseline in Hemoglobin Level Day 8; n=14, 15	-1.0 Grams per liter Standard Deviation 6.98	-1.3 Grams per liter Standard Deviation 4.37
Change From Baseline in Hemoglobin Level Day 28; n=13, 16	-2.5 Grams per liter Standard Deviation 8.76	-0.9 Grams per liter Standard Deviation 9.62
Change From Baseline in Hemoglobin Level Week 8; n=11, 16	-4.5 Grams per liter Standard Deviation 13.71	2.6 Grams per liter Standard Deviation 12.48
Change From Baseline in Hemoglobin Level Week 12; n=12, 14	-1.0 Grams per liter Standard Deviation 12.59	2.1 Grams per liter Standard Deviation 11.02
Change From Baseline in Hemoglobin Level Week 16; n=12 16	0.0 Grams per liter Standard Deviation 15.47	1.9 Grams per liter Standard Deviation 10.14
Change From Baseline in Hemoglobin Level Week 24; n=11, 15	-0.6 Grams per liter Standard Deviation 10.60	1.5 Grams per liter Standard Deviation 8.82
Change From Baseline in Hemoglobin Level Week 32; n=11, 13	-2.4 Grams per liter Standard Deviation 10.66	1.5 Grams per liter Standard Deviation 9.49
Change From Baseline in Hemoglobin Level Week 40; n=8, 12	-0.9 Grams per liter Standard Deviation 12.14	0.7 Grams per liter Standard Deviation 11.32
Change From Baseline in Hemoglobin Level Week 48; n=8, 13	0.0 Grams per liter Standard Deviation 9.80	0.5 Grams per liter Standard Deviation 13.48
Change From Baseline in Hemoglobin Level Week 60; n=5, 12	-1.8 Grams per liter Standard Deviation 13.99	5.0 Grams per liter Standard Deviation 13.22
Change From Baseline in Hemoglobin Level Week 72; n=3, 4	-4.3 Grams per liter Standard Deviation 7.37	7.0 Grams per liter Standard Deviation 8.72
Change From Baseline in Hemoglobin Level Week 84; n=0, 1	—	-6.0 Grams per liter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles)

Blood samples were collected for the analysis of hematology parameters such as hematocrit level. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Change From Baseline in Hematocrit Level Baseline; n=14, 16	0.4024 Proportion of red blood cells in blood Standard Deviation 0.05259	0.3974 Proportion of red blood cells in blood Standard Deviation 0.06496
Change From Baseline in Hematocrit Level Day 8; n=14, 15	-0.0015 Proportion of red blood cells in blood Standard Deviation 0.02666	-0.0049 Proportion of red blood cells in blood Standard Deviation 0.01515
Change From Baseline in Hematocrit Level Day 28; n=13, 16	-0.0066 Proportion of red blood cells in blood Standard Deviation 0.03105	-0.0043 Proportion of red blood cells in blood Standard Deviation 0.03313
Change From Baseline in Hematocrit Level Week 8; n=11, 16	-0.0105 Proportion of red blood cells in blood Standard Deviation 0.04383	0.0092 Proportion of red blood cells in blood Standard Deviation 0.04092
Change From Baseline in Hematocrit Level Week 12; n=12, 14	-0.0027 Proportion of red blood cells in blood Standard Deviation 0.03702	0.0054 Proportion of red blood cells in blood Standard Deviation 0.03419
Change From Baseline in Hematocrit Level Week 16; n=12, 16	-0.0033 Proportion of red blood cells in blood Standard Deviation 0.04275	0.0021 Proportion of red blood cells in blood Standard Deviation 0.03054
Change From Baseline in Hematocrit Level Week 24; n=11, 15	-0.0025 Proportion of red blood cells in blood Standard Deviation 0.03707	0.0062 Proportion of red blood cells in blood Standard Deviation 0.02787
Change From Baseline in Hematocrit Level Week 32; n=11, 13	-0.0081 Proportion of red blood cells in blood Standard Deviation 0.03310	0.0062 Proportion of red blood cells in blood Standard Deviation 0.03144
Change From Baseline in Hematocrit Level Week 40; n=8, 12	-0.0005 Proportion of red blood cells in blood Standard Deviation 0.03257	0.0063 Proportion of red blood cells in blood Standard Deviation 0.03601
Change From Baseline in Hematocrit Level Week 48; n=8, 13	0.0065 Proportion of red blood cells in blood Standard Deviation 0.02919	0.0078 Proportion of red blood cells in blood Standard Deviation 0.04331
Change From Baseline in Hematocrit Level Week 60; n=5, 12	-0.0024 Proportion of red blood cells in blood Standard Deviation 0.04000	0.0200 Proportion of red blood cells in blood Standard Deviation 0.04520
Change From Baseline in Hematocrit Level Week 72; n=3, 4	-0.0170 Proportion of red blood cells in blood Standard Deviation 0.03119	0.0248 Proportion of red blood cells in blood Standard Deviation 0.02943
Change From Baseline in Hematocrit Level Week 84; n=0, 1	—	-0.0090 Proportion of red blood cells in blood Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles)

Blood samples were collected for the analysis of hematology parameters such as mean corpuscle volume. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Change From Baseline in Mean Corpuscle Volume Baseline; n=14, 16	99.1 Femtoliter Standard Deviation 8.83	97.8 Femtoliter Standard Deviation 9.28
Change From Baseline in Mean Corpuscle Volume Day 8; n=14, 15	0.1 Femtoliter Standard Deviation 2.35	0.3 Femtoliter Standard Deviation 1.71
Change From Baseline in Mean Corpuscle Volume Day 28; n=13, 16	1.2 Femtoliter Standard Deviation 3.26	0.3 Femtoliter Standard Deviation 3.82
Change From Baseline in Mean Corpuscle Volume Week 8; n=11, 16	0.3 Femtoliter Standard Deviation 3.77	-0.3 Femtoliter Standard Deviation 6.02
Change From Baseline in Mean Corpuscle Volume Week 12; n=12, 14	1.1 Femtoliter Standard Deviation 7.73	-1.5 Femtoliter Standard Deviation 7.39
Change From Baseline in Mean Corpuscle Volume Week 16; n=12, 16	0.3 Femtoliter Standard Deviation 7.84	-2.2 Femtoliter Standard Deviation 8.85
Change From Baseline in Mean Corpuscle Volume Week 24; n=11, 15	-0.3 Femtoliter Standard Deviation 8.25	-2.0 Femtoliter Standard Deviation 10.36
Change From Baseline in Mean Corpuscle Volume Week 32; n=11, 13	-1.0 Femtoliter Standard Deviation 8.54	-2.4 Femtoliter Standard Deviation 10.87
Change From Baseline in Mean Corpuscle Volume Week 40; n=8, 12	2.5 Femtoliter Standard Deviation 8.75	-0.7 Femtoliter Standard Deviation 11.41
Change From Baseline in Mean Corpuscle Volume Week 48; n=8, 13	2.0 Femtoliter Standard Deviation 7.76	-1.0 Femtoliter Standard Deviation 11.73
Change From Baseline in Mean Corpuscle Volume Week 60; n=5, 12	1.4 Femtoliter Standard Deviation 7.89	-1.2 Femtoliter Standard Deviation 11.82
Change From Baseline in Mean Corpuscle Volume Week 72; n=3, 4	0.3 Femtoliter Standard Deviation 10.12	2.3 Femtoliter Standard Deviation 14.10
Change From Baseline in Mean Corpuscle Volume Week 84; n=0, 1	—	18.0 Femtoliter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles)

Blood samples were collected for the analysis of hematology parameters such as RBC. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Outcome measures

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Change From Baseline in Red Blood Cell Count Baseline; n=14, 16	4.09 Trillion cells per liter Standard Deviation 0.550	4.09 Trillion cells per liter Standard Deviation 0.731
Change From Baseline in Red Blood Cell Count Day 8; n=14, 15	0.00 Trillion cells per liter Standard Deviation 0.254	-0.04 Trillion cells per liter Standard Deviation 0.140
Change From Baseline in Red Blood Cell Count Day 28; n=13, 16	-0.08 Trillion cells per liter Standard Deviation 0.309	-0.06 Trillion cells per liter Standard Deviation 0.318
Change From Baseline in Red Blood Cell Count Week 8; n=11, 16	-0.14 Trillion cells per liter Standard Deviation 0.434	0.12 Trillion cells per liter Standard Deviation 0.435
Change From Baseline in Red Blood Cell Count Week 12; n=12, 14	-0.05 Trillion cells per liter Standard Deviation 0.493	0.15 Trillion cells per liter Standard Deviation 0.477
Change From Baseline in Red Blood Cell Count Week 16; n=12, 16	-0.03 Trillion cells per liter Standard Deviation 0.529	0.13 Trillion cells per liter Standard Deviation 0.478
Change From Baseline in Red Blood Cell Count Week 24; n=11, 15	0.02 Trillion cells per liter Standard Deviation 0.464	0.18 Trillion cells per liter Standard Deviation 0.514
Change From Baseline in Red Blood Cell Count Week 32; n=11, 13	-0.04 Trillion cells per liter Standard Deviation 0.467	0.18 Trillion cells per liter Standard Deviation 0.504
Change From Baseline in Red Blood Cell Count Week 40; n=8, 12	-0.08 Trillion cells per liter Standard Deviation 0.392	0.09 Trillion cells per liter Standard Deviation 0.658
Change From Baseline in Red Blood Cell Count Week 48; n=8, 13	-0.00 Trillion cells per liter Standard Deviation 0.334	0.15 Trillion cells per liter Standard Deviation 0.625
Change From Baseline in Red Blood Cell Count Week 60; n=5, 12	-0.06 Trillion cells per liter Standard Deviation 0.428	0.28 Trillion cells per liter Standard Deviation 0.625
Change From Baseline in Red Blood Cell Count Week 72; n=3, 4	-0.20 Trillion cells per liter Standard Deviation 0.173	0.25 Trillion cells per liter Standard Deviation 0.759
Change From Baseline in Red Blood Cell Count Week 84; n=0, 1	—	-0.60 Trillion cells per liter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.

Adverse Events

DTG 50mg BID

Serious events: 5 serious events

Other events: 11 other events

Deaths: 2 deaths

Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Week 24; n=11, 15	-24.4 International units per liter Standard Deviation 82.07	-6.0 International units per liter Standard Deviation 67.29
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Baseline; n=14, 16	91.9 International units per liter Standard Deviation 29.64	114.9 International units per liter Standard Deviation 106.74
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Day 8; n=13, 15	1.9 International units per liter Standard Deviation 14.01	-1.2 International units per liter Standard Deviation 9.41
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Day 28; n=13, 16	-6.1 International units per liter Standard Deviation 10.71	-0.6 International units per liter Standard Deviation 11.37
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Week 8; n=11, 16	1.6 International units per liter Standard Deviation 15.6	20.6 International units per liter Standard Deviation 63.97
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Week 12; n=12, 14	-0.8 International units per liter Standard Deviation 10.19	-0.3 International units per liter Standard Deviation 26.15
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Week 16; n=10, 16	3.1 International units per liter Standard Deviation 12.02	8.2 International units per liter Standard Deviation 40.55
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Week 24; n=11, 15	1.7 International units per liter Standard Deviation 21.72	3.3 International units per liter Standard Deviation 54.06
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Week 32; n=11, 14	6.9 International units per liter Standard Deviation 19.74	20.5 International units per liter Standard Deviation 35.89
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Week 40; n=8, 12	2.3 International units per liter Standard Deviation 20.26	7.8 International units per liter Standard Deviation 24.69
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Week 48; n=8, 13	28.0 International units per liter Standard Deviation 67.54	13.8 International units per liter Standard Deviation 32.07
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Week 60; n=5, 12	6.0 International units per liter Standard Deviation 23.86	12.8 International units per liter Standard Deviation 35.98
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Week 72; n=3, 4	-5.0 International units per liter Standard Deviation 19.29	15.3 International units per liter Standard Deviation 10.21
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALP; Week 84; n=0, 1	—	22.0 International units per liter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Baseline; n=14, 16	24.9 International units per liter Standard Deviation 13.33	37.4 International units per liter Standard Deviation 22.70
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Day 8; n=13, 15	0.0 International units per liter Standard Deviation 7.02	-3.8 International units per liter Standard Deviation 11.91
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Day 28; n=13, 16	0.4 International units per liter Standard Deviation 15.45	-5.3 International units per liter Standard Deviation 23.65
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Week 8; n=11, 16	1.2 International units per liter Standard Deviation 20.30	-9.2 International units per liter Standard Deviation 17.93
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Week 12; n=12, 14	-5.4 International units per liter Standard Deviation 4.94	-8.7 International units per liter Standard Deviation 23.36
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Week 16; n=10, 16	-5.2 International units per liter Standard Deviation 3.97	-10.1 International units per liter Standard Deviation 23.02
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Week 24; n=11, 15	3.1 International units per liter Standard Deviation 18.66	-14.5 International units per liter Standard Deviation 23.16
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Week 32; n=11, 14	0.9 International units per liter Standard Deviation 14.01	-10.6 International units per liter Standard Deviation 25.77
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Week 40; n=8, 12	-1.6 International units per liter Standard Deviation 8.75	-7.7 International units per liter Standard Deviation 25.86
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Week 48; n=8, 13	7.9 International units per liter Standard Deviation 20.02	-9.2 International units per liter Standard Deviation 23.50
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Week 60; n=5, 12	0.8 International units per liter Standard Deviation 7.19	-8.3 International units per liter Standard Deviation 24.28
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Week 72; n=3, 4	8.7 International units per liter Standard Deviation 17.67	-29.3 International units per liter Standard Deviation 33.06
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase ALT; Week 84; n=0, 1	—	-3.0 International units per liter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Baseline; n=14, 16	28.9 International units per liter Standard Deviation 11.13	34.9 International units per liter Standard Deviation 14.35
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Day 8; n=13, 15	1.0 International units per liter Standard Deviation 11.50	-2.0 International units per liter Standard Deviation 9.17
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Day 28; n=13, 16	-4.0 International units per liter Standard Deviation 10.13	-2.3 International units per liter Standard Deviation 17.08
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Week 8; n=11, 16	-2.9 International units per liter Standard Deviation 7.57	-6.3 International units per liter Standard Deviation 9.64
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Week 12; n=12, 14	-4.8 International units per liter Standard Deviation 4.07	-5.1 International units per liter Standard Deviation 11.78
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Week 16; n=10, 16	-4.0 International units per liter Standard Deviation 2.94	-6.6 International units per liter Standard Deviation 12.27
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Week 24; n=11, 15	1.7 International units per liter Standard Deviation 14.05	-10.1 International units per liter Standard Deviation 11.87
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Week 32; n=11, 14	-1.7 International units per liter Standard Deviation 6.83	-7.4 International units per liter Standard Deviation 13.14
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Week 40; n=8, 12	-4.9 International units per liter Standard Deviation 4.09	-4.1 International units per liter Standard Deviation 12.46
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Week 48; n=8, 13	9.0 International units per liter Standard Deviation 27.77	-5.4 International units per liter Standard Deviation 10.47
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Week 60; n=5, 12	-3.2 International units per liter Standard Deviation 1.64	-5.9 International units per liter Standard Deviation 9.24
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Week 72; n=3, 4	1.3 International units per liter Standard Deviation 8.50	-13.8 International units per liter Standard Deviation 12.31
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase AST; Week 84; n=0, 1	—	-8.0 International units per liter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Baseline; n=14, 16	162.4 International units per liter Standard Deviation 129.21	130.3 International units per liter Standard Deviation 76.46
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Day 8; n=13, 15	-2.1 International units per liter Standard Deviation 122.28	-1.5 International units per liter Standard Deviation 53.29
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Day 28; n=13, 16	-35.6 International units per liter Standard Deviation 96.22	37.0 International units per liter Standard Deviation 123.10
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Week 8; n=11, 16	-16.4 International units per liter Standard Deviation 106.99	-7.3 International units per liter Standard Deviation 68.19
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Week 12; n=12, 14	-18.8 International units per liter Standard Deviation 105.64	0.4 International units per liter Standard Deviation 84.85
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Week 16; n=10, 16	34.2 International units per liter Standard Deviation 81.44	80.5 International units per liter Standard Deviation 305.19
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Week 32; n=11, 14	2.3 International units per liter Standard Deviation 54.41	23.4 International units per liter Standard Deviation 96.88
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Week 40; n=8, 12	-50.0 International units per liter Standard Deviation 93.45	66.3 International units per liter Standard Deviation 168.54
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Week 48; n=8, 13	7.8 International units per liter Standard Deviation 71.57	16.1 International units per liter Standard Deviation 68.96
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Week 60; n=5, 12	-12.2 International units per liter Standard Deviation 23.30	18.8 International units per liter Standard Deviation 86.19
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Week 72; n=3, 4	35.0 International units per liter Standard Deviation 68.61	-29.0 International units per liter Standard Deviation 76.27
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase Creatine Kinase; Week 84; n=0, 1	—	-134.0 International units per liter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.

Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Baseline; n=14, 16	10.0 Micromoles per liter Standard Deviation 4.51	7.5 Micromoles per liter Standard Deviation 3.14
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Day 8; n=13, 15	0.8 Micromoles per liter Standard Deviation 6.81	-1.1 Micromoles per liter Standard Deviation 2.12
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Day 28; n=13, 16	-0.2 Micromoles per liter Standard Deviation 6.19	2.1 Micromoles per liter Standard Deviation 9.78
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Week 8; n=11, 16	0.0 Micromoles per liter Standard Deviation 4.20	3.1 Micromoles per liter Standard Deviation 13.76
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Week 12; n=12, 14	0.5 Micromoles per liter Standard Deviation 4.76	-0.6 Micromoles per liter Standard Deviation 2.14
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Week 16; n=10, 16	0.6 Micromoles per liter Standard Deviation 3.89	1.9 Micromoles per liter Standard Deviation 10.89
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Week 24; n=11, 15	0.2 Micromoles per liter Standard Deviation 2.89	2.1 Micromoles per liter Standard Deviation 8.19
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Week 32; n=11, 14	-0.4 Micromoles per liter Standard Deviation 3.20	2.3 Micromoles per liter Standard Deviation 10.16
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Week 40; n=8, 12	0.0 Micromoles per liter Standard Deviation 3.70	3.3 Micromoles per liter Standard Deviation 12.43
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Week 48; n=8, 13	-0.8 Micromoles per liter Standard Deviation 4.13	3.2 Micromoles per liter Standard Deviation 12.18
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Week 60; n=5, 12	-2.4 Micromoles per liter Standard Deviation 2.61	2.3 Micromoles per liter Standard Deviation 11.63
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Week 72; n=3, 4	-1.3 Micromoles per liter Standard Deviation 4.16	9.5 Micromoles per liter Standard Deviation 16.36
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels T. Bil.; Week 84; n=0, 1	—	2.0 Micromoles per liter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Baseline; n=14, 16	86.94 Micromoles per liter Standard Deviation 18.971	88.96 Micromoles per liter Standard Deviation 24.013
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Day 8; n=13, 15	10.96 Micromoles per liter Standard Deviation 24.505	0.11 Micromoles per liter Standard Deviation 14.873
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Day 28; n=13, 16	12.72 Micromoles per liter Standard Deviation 19.697	13.58 Micromoles per liter Standard Deviation 21.030
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Week 8; n=11, 16	12.15 Micromoles per liter Standard Deviation 8.570	15.79 Micromoles per liter Standard Deviation 19.574
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Week 12; n=12, 14	6.86 Micromoles per liter Standard Deviation 9.153	9.85 Micromoles per liter Standard Deviation 13.274
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Week 16; n=10, 16	8.22 Micromoles per liter Standard Deviation 13.464	7.68 Micromoles per liter Standard Deviation 13.031
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Week 24; n=11, 15	1.63 Micromoles per liter Standard Deviation 11.098	13.31 Micromoles per liter Standard Deviation 17.347
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Week 32; n=11, 14	0.98 Micromoles per liter Standard Deviation 7.441	15.96 Micromoles per liter Standard Deviation 11.902
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Week 40; n=8, 12	3.58 Micromoles per liter Standard Deviation 10.788	12.94 Micromoles per liter Standard Deviation 13.870
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Week 48; n=8, 13	4.21 Micromoles per liter Standard Deviation 19.450	12.85 Micromoles per liter Standard Deviation 9.128
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Week 60; n=5, 12	4.96 Micromoles per liter Standard Deviation 5.560	11.72 Micromoles per liter Standard Deviation 15.820
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Week 72; n=3, 4	0.93 Micromoles per liter Standard Deviation 8.529	13.25 Micromoles per liter Standard Deviation 16.957
Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels Creatinine; Week 84; n=0, 1	—	1.80 Micromoles per liter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.

Measure	DTG 50mg BID n=14 participants at risk Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 participants at risk Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Cardiac disorders Coronary artery disease	7.1% 1/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Gastrointestinal disorders Diarrhoea	7.1% 1/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
General disorders Cardiac death	7.1% 1/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Injury, poisoning and procedural complications Multiple fractures	0.00% 0/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	6.2% 1/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	6.2% 1/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Nervous system disorders Brain injury	0.00% 0/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	6.2% 1/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Renal and urinary disorders Renal failure acute	7.1% 1/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	7.1% 1/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Cardiac disorders Cardiac arrest	7.1% 1/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
General disorders Chest pain	7.1% 1/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Injury, poisoning and procedural complications Pulmonary contusion	0.00% 0/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	6.2% 1/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	6.2% 1/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Herpes zoster	0.00% 0/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	6.2% 1/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Perirectal abscess	0.00% 0/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	6.2% 1/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Pneumonia	7.1% 1/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Hepatobiliary disorders Cholecystitis	0.00% 0/14 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.	6.2% 1/16 • Serious adverse events (SAEs) and non-serious AEs were collected in the time period from the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks). SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.

Outcome measures
Measure	DTG 50 mg BID n=14 Participants Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.	Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase n=16 Participants Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen HDL Cholesterol; Week 12; n=6, 8	0.117 Millimoles per liter Standard Deviation 0.0683	0.156 Millimoles per liter Standard Deviation 0.2485
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Week 8; n=11, 16	1.2 Millimoles per liter Standard Deviation 1.66	1.6 Millimoles per liter Standard Deviation 3.40
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Cholesterol; Baseline; n=8, 10	3.819 Millimoles per liter Standard Deviation 0.9219	4.725 Millimoles per liter Standard Deviation 1.7430
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Cholesterol; Week 12; n=6, 8	0.433 Millimoles per liter Standard Deviation 0.4622	0.538 Millimoles per liter Standard Deviation 0.9598
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Cholesterol; Week 24; n=6, 10	0.308 Millimoles per liter Standard Deviation 0.3137	0.585 Millimoles per liter Standard Deviation 1.0296
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Cholesterol; Week 48; n=3, 7	0.567 Millimoles per liter Standard Deviation 0.2021	0.421 Millimoles per liter Standard Deviation 1.2770
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Cholesterol; Week 60; n=2, 5	0.375 Millimoles per liter Standard Deviation 0.9546	-0.020 Millimoles per liter Standard Deviation 1.3326
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Cholesterol; Week 72; n=0, 1	—	1.350 Millimoles per liter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Baseline; n=14, 16	104.1 Millimoles per liter Standard Deviation 1.59	105.4 Millimoles per liter Standard Deviation 3.32
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Day 8; n=13, 15	0.5 Millimoles per liter Standard Deviation 1.61	0.4 Millimoles per liter Standard Deviation 2.03
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Day 28; n=13, 16	0.4 Millimoles per liter Standard Deviation 2.26	-0.5 Millimoles per liter Standard Deviation 2.58
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Week 8; n=11, 16	0.5 Millimoles per liter Standard Deviation 1.97	-1.8 Millimoles per liter Standard Deviation 3.08
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Week 12; n=12, 14	-0.8 Millimoles per liter Standard Deviation 1.71	0.1 Millimoles per liter Standard Deviation 2.73
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Week 16; n=10, 16	1.4 Millimoles per liter Standard Deviation 1.90	-1.0 Millimoles per liter Standard Deviation 2.73
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Week 24; n=11, 15	0.9 Millimoles per liter Standard Deviation 1.45	-1.2 Millimoles per liter Standard Deviation 3.14
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Week 32; n=11, 14	1.1 Millimoles per liter Standard Deviation 2.21	0.0 Millimoles per liter Standard Deviation 2.57
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Week 40; n=8, 12	0.5 Millimoles per liter Standard Deviation 2.51	1.3 Millimoles per liter Standard Deviation 2.80
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Week 48; n=8, 13	1.5 Millimoles per liter Standard Deviation 3.74	-0.1 Millimoles per liter Standard Deviation 3.38
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Week 60; n=5, 12	2.0 Millimoles per liter Standard Deviation 2.12	1.1 Millimoles per liter Standard Deviation 2.81
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Week 72; n=3, 4	2.0 Millimoles per liter Standard Deviation 2.65	1.0 Millimoles per liter Standard Deviation 2.94
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Chloride; Week 84; n=0, 1	—	-2.0 Millimoles per liter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Baseline; n=14, 16	22.5 Millimoles per liter Standard Deviation 2.07	20.8 Millimoles per liter Standard Deviation 4.12
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Day 8; n=13, 15	0.2 Millimoles per liter Standard Deviation 1.30	0.1 Millimoles per liter Standard Deviation 2.25
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Day 28; n=13, 16	0.4 Millimoles per liter Standard Deviation 2.29	1.1 Millimoles per liter Standard Deviation 2.47
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Week 12; n=12, 14	1.7 Millimoles per liter Standard Deviation 1.92	1.9 Millimoles per liter Standard Deviation 2.73
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Week 16; n=10, 16	-0.2 Millimoles per liter Standard Deviation 2.39	1.8 Millimoles per liter Standard Deviation 3.42
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Week 24; n=11, 15	0.9 Millimoles per liter Standard Deviation 1.92	1.5 Millimoles per liter Standard Deviation 2.92
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Week 32; n=11, 14	1.5 Millimoles per liter Standard Deviation 2.21	0.8 Millimoles per liter Standard Deviation 2.69
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Week 40; n=8, 12	0.9 Millimoles per liter Standard Deviation 2.30	-0.2 Millimoles per liter Standard Deviation 2.25
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Week 48; n=8, 13	-0.4 Millimoles per liter Standard Deviation 2.13	1.7 Millimoles per liter Standard Deviation 3.01
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Week 60; n=5, 12	0.8 Millimoles per liter Standard Deviation 1.30	0.3 Millimoles per liter Standard Deviation 2.42
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Week 72; n=3, 4	2.0 Millimoles per liter Standard Deviation 3.61	-0.3 Millimoles per liter Standard Deviation 1.89
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen CO2/HCO3; Week 84; n=0, 1	—	4.0 Millimoles per liter Standard Deviation NA Only one participant was analyzed for this treatment arm at this time point; thus, no standard deviation could be calculated for this single participant.
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Glucose; Baseline; n=12, 16	4.84 Millimoles per liter Standard Deviation 0.535	5.56 Millimoles per liter Standard Deviation 1.994
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Glucose; Week 12; n=11, 14	-0.01 Millimoles per liter Standard Deviation 0.677	0.04 Millimoles per liter Standard Deviation 0.679
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Glucose; Week 24; n=10, 15	0.17 Millimoles per liter Standard Deviation 0.957	-0.08 Millimoles per liter Standard Deviation 1.024
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Glucose; Week 48; n=7, 13	0.13 Millimoles per liter Standard Deviation 0.439	0.40 Millimoles per liter Standard Deviation 1.143
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Glucose; Week 60; n=3, 12	0.20 Millimoles per liter Standard Deviation 0.300	-0.18 Millimoles per liter Standard Deviation 0.723
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen Glucose; Week 72; n=2, 4	0.45 Millimoles per liter Standard Deviation 0.071	0.20 Millimoles per liter Standard Deviation 0.744
Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen HDL Cholesterol; Baseline; n=8, 10	0.956 Millimoles per liter Standard Deviation 0.2718	1.090 Millimoles per liter Standard Deviation 0.2846