SAILING: A Study of GSK1349572 Versus Raltegravir (RAL) With Investigator Selected Background Regimen in Antiretroviral-Experienced, Integrase Inhibitor-Naive Adults

• Sponsor: ViiV Healthcare (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01231516
• Collaborator: Shionogi (Industry), GlaxoSmithKline (Industry)
• Enrollment: 724
• Locations: 181
• Arms: 2
• Actual Duration (Months): 123.3
• Patients Per Site: 4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

ING111762 is a 48 week, randomized, double-blind, active-controlled, multicenter, parallel group, non-inferiority study. The study will be conducted in at least 688 HIV-1 infected antiretroviral experienced, integrase-naïve subjects. Subjects will be randomized 1:1 to receive GSK1349572 50 mg once daily or raltegravir (RAL) 400 mg twice daily, each added to an investigator selected background regimen consisting of at least one fully active agent plus no more than one second single agent which may or may not be active. Antiviral activity, safety, pharmacokinetics (PK), and development of viral resistance will be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Infection, Human Immunodeficiency Virus; HIV Infections	Drug: GSK1349572; Drug: Raltegravir; Drug: GSK1349572 Placebo; Drug: Raltegravir Placebo	Phase 3

Detailed Description

ING111762 is a 48 week, randomized, double-blind, active-controlled, multicenter, parallel group, non-inferiority study. The study will be conducted in at least 688 HIV-1 infected antiretroviral experienced, integrase-naïve subjects. Subjects will be randomized 1:1 to receive GSK1349572 50 mg once daily or raltegravir (RAL) 400 mg twice daily, each added to an investigator selected background regimen consisting of at least one fully active agent plus no more than one second single agent which may or may not be active. Antiviral activity, safety, pharmacokinetics (PK), and development of viral resistance will be evaluated.

Subjects must have documented genotypic or phenotypic resistance to at least one member of each of at least two antiretroviral therapy (ART) drug classes [nucleoside/nucleotide reverse transcriptase inhibitor (N[t]RTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI), fusion inhibitor (T20), or entry inhibitor (chemokine receptor 5 [CCR5] antagonist)].

The primary analysis will take place after the last subject completes 48 weeks on therapy. An additional data cut and analysis will be conducted after the last subject completes 24 weeks on therapy.

Subjects randomized to GSK1349572 who successfully complete Week 48 will continue to received GSK1349572 until either it is locally available, until they no longer derive clinical benefit, until they meet a protocol-defined reason for discontinuation, or until development of the compound is terminated.

ViiV Healthcare is the sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship

Study Design

• Study Type: Interventional
• Actual Enrollment: 724 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind Study of the Safety and Efficacy of GSK1349572 50 mg Once Daily Versus Raltegravir 400 mg Twice Daily, Both Administered With an Investigator-selected Background Regimen Over 48 Weeks in HIV-1 Infected, Integrase Inhibitor-Naïve, Antiretroviral-Experienced Adults
• Actual Study Start Date: Oct 26, 2010
• Actual Primary Completion Date: Feb 4, 2013
• Actual Study Completion Date: Feb 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK1349572 + Raltegravir Placebo Subjects will receive GSK1349572 50mg once daily plus raltegravir placebo twice daily.	Drug: GSK1349572; 50mg once daily; Drug: Raltegravir Placebo; Inactive placebo tablet twice daily
Active Comparator: Raltegravir + GSK1349572 Placebo Subjects will receive raltegravir 400mg twice daily plus GSK1349572 placebo once daily.	Drug: Raltegravir; 400mg twice daily; Drug: GSK1349572 Placebo; Inactive placebo tablet once daily

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48 [At Week 48]

   The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 c/mL at Week 48 was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the randomized phase of the study.

Secondary Outcome Measures

1. Number of Participants (Par.) With Detectable Virus That Has Genotypic or Phenotypic Evidence of Treatment-emergent Integrase Inhibitor (INI) Resistance at Time of Protocol Defined Virology Failure (PDVF) [Baseline (Day 1) until PDVF (Up to Week 48)]

   For par. meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure and Baseline 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 logarithm to base 10 (log10) copies/mL by Week 16, 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.

2. Number of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24 [At Week 24]

   The number of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 c/mL at Week 24 was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA at Week 24 as nonresponders, as well as participants who switched their concomitant ART prior to Week 24 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA measurement through Week 24 (within window) while the participant was on-treatment. The result below corresponds to the Week 24 interim analysis.

3. Number of Participants With Plasma HIV-1 RNA <400 c/mL at Week 24 and Week 48 [At Week 24 and Week 48]

   The number of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <400 c/mL at the visit of interest was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA at the visit of interest as nonresponders, as well as participants who switched their concomitant ART prior to the visit of interest as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA measurment (within window) for the timepoint of interest while the participant was on-treatment.

4. Absolute Values of Cluster of Differentiation 4+ (CD4+) Cell Counts at Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 96 and 144 [Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 96 and 144]

   Blood samples were collected at specified time points to assess CD4+ using flow cytometry. Median and interquartile range are presented. Baseline was the latest pre-dose assessment value (Day 1).

5. Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12,16, 24, 32, 40, 48, 96 and 144 [Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 96 and 144]

   Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline was the latest pre-dose assessment value (Day 1). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Median and interquartile range is presented.

6. Number of Participants With Post-Baseline HIV-associated Conditions, Excluding Recurrences, and Disease Progressions [Up to Week 480]

   Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of following conditions (CON), without any CON listed in Categories B and C: Asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: Symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C:Clinical CON listed in acquired immunodeficiency syndrome (AIDS) surveillance case definition. Indicators of CDP defined as:CDC CAT A at Baseline (BS) to CDC CAT C event (EV); CDC CAT B at BS to CDC CAT C EV; CDC CAT C at BS to new CDC CAT C EV; or CDC CAT A, B, or C at BS to death.

7. Number of Participants With Post-Baseline Emergent Grade 1 to 4 Clinical Chemistry and Hematology Toxicities [From Baseline (Day 1) until Week 48, including participants with post-treatment events occurring after Week 48 for participants not entering the post-Week 48 Open-Label phase of the study]

   All Grade 1 to 4 post-Baseline-emergent chemistry toxicities included alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), asparate aminotransferase (AST), carbon dioxide (CO2) content/bicarbonate, cholesterol, creatine kinase (CK), creatinine, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol calculation, lipase, total bilirubin, and triglycerides. All Grade 1 to 4 post-Baseline-emergent hematology toxities included hemoglobin, platelet count, total neutrophils, and white blood cell count. The Division of AIDS (DAIDS) defined toxicity grades as follows: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening; Grade 5, death. Higher the grade, more severe the symptoms.

8. Number of Participants With Post-Baseline Emergent Grade 1 to 4 Clinical Chemistry and Hematology Toxicities [From Week 48 to Week 480]

   Blood samples were collected for the analysis of clinical chemistry and hematology parameters: Alanine aminotransferase (ALT), albumin, alkaline phosphate (ALP), aspartate aminotransferase (AST), carbon dioxide (CO2) content/bicarbonate, cholesterol, creatine kinase (CK), creatinine, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hypoonatremia, LDL cholesterol, lipase, total bilirubin, triglycerides, hemoglibin, neutrophils, platelets, white blood cells. Any abnormality in clinical chemistry and hematology parameters were evaluated according to the DAIDS toxicity scale From Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening).Higher the grade, more severe the symptoms.

9. DTG PK Parameters Including Maximum Plasma Drug Concentration (Cmax), Minimal Plasma Drug Concentration (Cmin), and Average Plasma Pre-dose Concentration (C0_avg) [Pre-dose and at 1 to 3 hours or 4 to 12 hours post-dose at Week 4; Pre-dose at Week 24; Pre-dose and 1 to 3 hours or 4 to 12 hours post-dose at Week 48]

   Cmax, Cmin and C0_avg were assessed by population pharmacokinetic (PK) modeling using sparse PK samples which were collected as follows: one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 4, one pre-dose sample at Week 24, and one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 48. Cmax, Cmin and C0_avg were estimated and reported here.

10. DTG PK Parameter Including Pre-dose Concentration (C0) [Pre-dose at Weeks 4, 24 and 48]

    C0 was assessed by population PK modeling using sparse PK samples which were collected as follows: one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 4, one pre-dose sample at Week 24, and one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 48. DTG predose concentration (C0) at Week 4, Week 24, and Week 48 was estimated and reported here.

11. DTG PK Parameters Including Area Under the Plasma Concentration-time Curve From Time Zero to Time Tau Over a Dosing Interval at Steady State (AUC[0-tau]) [Pre-dose and at 1 to 3 hours or 4 to 12 hours post-dose at Week 4; Pre-dose at Week 24; Pre-dose and 1 to 3 hours or 4 to 12 hours post-dose at Week 48]

    AUC is defined as the area under the DTG concentration-time curve as a measure of drug exposure over time. AUC(0-tau) is defined as the area under the plasma concentration-time curve from time zero to time tau over a dosing interval at steady state, where tau is the length of the dosing interval of DTG. AUC was assessed by population pharmacokinetic (PK) modeling using sparse PK samples which were collected as follows: one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 4, one pre-dose sample at Week 24, and one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 48.

12. Change From Baseline in European Quality of Life-5 Dimensions-3 Levels (EQ-5D-3L) Utility Score [Baseline (Day 1) and at Weeks 24 and 48]

    The EQ-5D-3L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 3 levels for each dimension including 1=no problems, 2=some problems, 3=extreme problems. The health state is defined by combining the levels of answers from each of the 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-3L utility score ranges from -0.594 to 1. Higher scores indicate better health. Baseline was the latest pre-dose assessment value (Day 1) and change from Baseline=post-dose value minus Baseline value.

13. Change From Baseline in European Quality of Life-5 Dimensions-3 Levels (EQ-5D-3L) Thermometer Scores [Baseline (Day 1) and at Weeks 24 and 48]

    The EQ-5D-3L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 3 levels for each dimension including 1=no problems, 2=some problems, 3=extreme problems. EQ-5D-3L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Participants were asked to rate their current health status using the visual analogue scale 'Thermometer'. Score ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). Higher scores indicate better heath. Baseline was the latest pre-dose assessment value (Day 1) and change from Baseline=post-dose value minus Baseline value.

Other Outcome Measures

1. Absolute Values of Cluster of Differentiation 8+ (CD8+) Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, and 48 [At Weeks 4, 8, 12, 16, 24, 32, 40, and 48]

   The absolute value data for CD8+ cell count was planned to be evaluated. The results for this outcome measure will never be posted.

2. Change From Baseline in CD8+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, and 48 [Baseline (Day 1); Weeks 4, 8, 12, 16, 24, 32, 40, and 48]

   Change from Baseline data for CD8+ cell count was planned to be evaluated. The results for this outcome measure will never be posted.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Antiretroviral therapy (ART)-experienced, Human Immunodeficiency Virus (HIV) -1 infected adults at least 18 years of age.

• Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol).

• HIV-1 infection as documented by HIV-1 RNA >400 copies/mL (c/mL) at Screening and with at least one consecutive HIV-1 RNA >400 c/mL within the four months prior to Screening (unless the Screening HIV-1 RNA is > 1000 c/mL where no additional plasma HIV-1 RNA assessment is needed).

• Have documented resistance (via Screening resistance test) to two or more different classes of antiretroviral agents. For subjects off ART for at least one month, if Screening resistance results provide a fully active agent and do not show two class resistance then historical resistance results from the subject's most recent resistance testing may be used, following consultation with the study virologist and /or medical monitor.

• Integrase inhibitor (INI)-naïve, defined as no prior exposure to any INI (e.g. RAL, elvitegravir, or GSK1349572).

• Able to provide written informed consent prior to Screening.

• French subjects: In France, subjects will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

• Screening resistance test result indicates no fully active antiviral agents are available for design of the background regimen.

• Subject-virus does not yield results using genotype/phenotype/tropism at Screening (assay data is essential for eligibility determination).

• Women who are breastfeeding.

• Any evidence of an active AIDS-defining condition (except cutaneous Kaposi's sarcoma not requiring systemic therapy or CD4+ <200c/mm3).

• Subjects with moderate to severe hepatic impairment as defined by Child-Pugh classification.

• Recent history (less than or equal to 3 months) of upper or lower gastrointestinal bleed, with the exception of anal or rectal bleeding.

• Anticipated need for hepatitis C therapy during the study.

• History or presence of allergy or intolerance to the study drugs or their components or drugs of their class.

• History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma; other localized malignancies require agreement between the investigator and study medical monitor for inclusion of the subject.

• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days prior to Screening.

• Treatment with any of the following agents within 28 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, any immunomodulator.

• Treatment with any agent, other than licensed ART, which has documented activity against HIV-1 in vitro within 28 days of first dose of investigational product.

• Exposure to an experimental drug and/or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the experimental test agent - whichever is longer, prior to the first dose of IP.

• French subjects recruited at sites in France will be excluded if the subject has participated in any study using an investigational drug and/or vaccine within 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine - whichever is longer - prior to screening for the study or the subject plans to participate simultaneously in another clinical study.

• Any acute or verified Grade 4 laboratory abnormality.

• Alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN).

• ALT greater than or equal to 3xULN and bilirubin greater than or equal to 1.5xULN (with >35% direct bilirubin).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35294
2	GSK Investigational Site	Phoenix	Arizona	United States	85012
3	GSK Investigational Site	Little Rock	Arkansas	United States	72207
4	GSK Investigational Site	Bakersfield	California	United States	93301
5	GSK Investigational Site	Beverly Hills	California	United States	90211
6	GSK Investigational Site	Long Beach	California	United States	90813
7	GSK Investigational Site	Los Angeles	California	United States	90036
8	GSK Investigational Site	Los Angeles	California	United States	90048
9	GSK Investigational Site	Los Angeles	California	United States	90069
10	GSK Investigational Site	Oakland	California	United States	94609
11	GSK Investigational Site	New Haven	Connecticut	United States	06520
12	GSK Investigational Site	Norwalk	Connecticut	United States	06850
13	GSK Investigational Site	Washington	District of Columbia	United States	20007
14	GSK Investigational Site	Washington	District of Columbia	United States	20009
15	GSK Investigational Site	Daytona Beach	Florida	United States	32117
16	GSK Investigational Site	Fort Lauderdale	Florida	United States	33308
17	GSK Investigational Site	Fort Lauderdale	Florida	United States	33316
18	GSK Investigational Site	Fort Pierce	Florida	United States	34982
19	GSK Investigational Site	Orlando	Florida	United States	32803
20	GSK Investigational Site	Orlando	Florida	United States	32806
21	GSK Investigational Site	West Palm Beach	Florida	United States	33401
22	GSK Investigational Site	Wilton Manors	Florida	United States	33305
23	GSK Investigational Site	Augusta	Georgia	United States	30912
24	GSK Investigational Site	Savannah	Georgia	United States	31401
25	GSK Investigational Site	Chicago	Illinois	United States	60612
26	GSK Investigational Site	Maywood	Illinois	United States	60153
27	GSK Investigational Site	Indianapolis	Indiana	United States	46202
28	GSK Investigational Site	Iowa City	Iowa	United States	52242
29	GSK Investigational Site	Springfield	Massachusetts	United States	01105
30	GSK Investigational Site	Detroit	Michigan	United States	48202
31	GSK Investigational Site	Lansing	Michigan	United States	48911
32	GSK Investigational Site	Minneapolis	Minnesota	United States	55404
33	GSK Investigational Site	Minneapolis	Minnesota	United States	55415
34	GSK Investigational Site	Kansas City	Missouri	United States	64106
35	GSK Investigational Site	Saint Louis	Missouri	United States	63108
36	GSK Investigational Site	Omaha	Nebraska	United States	68106
37	GSK Investigational Site	Hillsborough	New Jersey	United States	08844
38	GSK Investigational Site	Neptune	New Jersey	United States	07753
39	GSK Investigational Site	Newark	New Jersey	United States	07102
40	GSK Investigational Site	Newark	New Jersey	United States	07103
41	GSK Investigational Site	Bronx	New York	United States	10467
42	GSK Investigational Site	New York	New York	United States	10003
43	GSK Investigational Site	New York	New York	United States	10011
44	GSK Investigational Site	Valhalla	New York	United States	10595
45	GSK Investigational Site	Chapel Hill	North Carolina	United States	27514
46	GSK Investigational Site	Charlotte	North Carolina	United States	28207
47	GSK Investigational Site	Charlotte	North Carolina	United States	28209
48	GSK Investigational Site	Durham	North Carolina	United States	27710
49	GSK Investigational Site	Greenville	North Carolina	United States	27834
50	GSK Investigational Site	Akron	Ohio	United States	44304
51	GSK Investigational Site	Cincinnati	Ohio	United States	45267
52	GSK Investigational Site	Portland	Oregon	United States	97210
53	GSK Investigational Site	Allentown	Pennsylvania	United States	18102
54	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19104
55	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19140
56	GSK Investigational Site	Providence	Rhode Island	United States	02906
57	GSK Investigational Site	Dallas	Texas	United States	75204
58	GSK Investigational Site	Dallas	Texas	United States	75246
59	GSK Investigational Site	Fort Worth	Texas	United States	76104
60	GSK Investigational Site	Houston	Texas	United States	77004
61	GSK Investigational Site	Houston	Texas	United States	77098
62	GSK Investigational Site	Houston	Texas	United States	77401
63	GSK Investigational Site	Longview	Texas	United States	75605
64	GSK Investigational Site	San Antonio	Texas	United States	78229
65	GSK Investigational Site	Salt Lake City	Utah	United States	84132
66	GSK Investigational Site	Annandale	Virginia	United States	22003
67	GSK Investigational Site	Seattle	Washington	United States	98104
68	GSK Investigational Site	Spokane	Washington	United States	99204
69	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1264AAJ
70	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires	Argentina	C1405CKC
71	GSK Investigational Site	Ciudad de Buenos Aires	Buenos Aires	Argentina	C1202ABB
72	GSK Investigational Site	Rosario	Santa Fe	Argentina	2000
73	GSK Investigational Site	Buenos Aires		Argentina	1141
74	GSK Investigational Site	Ciudad Autonoma de Buenos Aires		Argentina	C1181ACH
75	GSK Investigational Site	Darlinghurst	New South Wales	Australia	2010
76	GSK Investigational Site	Melbourne	Victoria	Australia	3004
77	GSK Investigational Site	Antwerpen		Belgium	2000
78	GSK Investigational Site	Brussels		Belgium	1000
79	GSK Investigational Site	Charleroi		Belgium	6000
80	GSK Investigational Site	Liege		Belgium	4000
81	GSK Investigational Site	Belo Horizonte	Minas Gerais	Brazil	30130100
82	GSK Investigational Site	Curitiba	Paraná	Brazil	80240-280
83	GSK Investigational Site	Sao Paulo	São Paulo	Brazil	01246-090
84	GSK Investigational Site	Sao Paulo	São Paulo	Brazil	04040-002
85	GSK Investigational Site	Rio de Janeiro		Brazil	21040-360
86	GSK Investigational Site	Salvador		Brazil	40110-060
87	GSK Investigational Site	Santos		Brazil	11045-904
88	GSK Investigational Site	São Paulo		Brazil	04121-000
89	GSK Investigational Site	Vitoria		Brazil	29041-091
90	GSK Investigational Site	Vancouver	British Columbia	Canada	V6Z 2C7
91	GSK Investigational Site	Hamilton	Ontario	Canada	L8N3Z5
92	GSK Investigational Site	Toronto	Ontario	Canada	M4T 3A7
93	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2N2
94	GSK Investigational Site	Montreal	Quebec	Canada	H2L 5B1
95	GSK Investigational Site	Montreal	Quebec	Canada	H2W 1T8
96	GSK Investigational Site	Puente Alto - Santiago	Región Metro De Santiago	Chile	8207257
97	GSK Investigational Site	Santiago	Región Metro De Santiago	Chile	8320000
98	GSK Investigational Site	Santiago	Región Metro De Santiago	Chile	8330074
99	GSK Investigational Site	Santiago	Región Metro De Santiago	Chile	8900088
100	GSK Investigational Site	Santiago		Chile	8360159
101	GSK Investigational Site	Bordeaux		France	33000
102	GSK Investigational Site	Garches		France	92380
103	GSK Investigational Site	Le Kremlin Bicêtre cedex		France	94275
104	GSK Investigational Site	Le Kremlin-Bicêtre Cedex		France	94275
105	GSK Investigational Site	Marseille		France	13009
106	GSK Investigational Site	Nice		France	06202
107	GSK Investigational Site	Orléans		France	45100
108	GSK Investigational Site	Paris Cedex 10		France	75475
109	GSK Investigational Site	Paris Cedex 13		France	75651
110	GSK Investigational Site	Paris Cedex 20		France	75970
111	GSK Investigational Site	Paris		France	75018
112	GSK Investigational Site	Tourcoing cedex		France	59208
113	GSK Investigational Site	Athens		Greece	11527
114	GSK Investigational Site	Athens		Greece	161 21
115	GSK Investigational Site	Piraeus		Greece	18536
116	GSK Investigational Site	Rio, Patras		Greece	26504
117	GSK Investigational Site	Budapest		Hungary	1097
118	GSK Investigational Site	Modena	Emilia-Romagna	Italy	41100
119	GSK Investigational Site	Busto Arsizio (VA)	Lombardia	Italy	21052
120	GSK Investigational Site	Milano	Lombardia	Italy	20127
121	GSK Investigational Site	Monza	Lombardia	Italy	20900
122	GSK Investigational Site	Torino	Piemonte	Italy	10149
123	GSK Investigational Site	Cagliari	Sardegna	Italy	09121
124	GSK Investigational Site	Cuautitlán, Estado De México	Estado De México	Mexico	54800
125	GSK Investigational Site	León, Guanajuato	Guanajuato	Mexico	37320
126	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44280
127	GSK Investigational Site	Mexico City		Mexico	03720
128	GSK Investigational Site	Amsterdam		Netherlands	1105 AZ
129	GSK Investigational Site	Rotterdam		Netherlands	3079 DZ
130	GSK Investigational Site	Chorzow		Poland	41-500
131	GSK Investigational Site	Bucharest		Romania	021105
132	GSK Investigational Site	Bucharest		Romania	030303
133	GSK Investigational Site	Constanta		Romania	900709
134	GSK Investigational Site	Ekaterinburg		Russian Federation	620149
135	GSK Investigational Site	Kazan		Russian Federation	420097
136	GSK Investigational Site	Krasnodar		Russian Federation	350015
137	GSK Investigational Site	Moscow		Russian Federation	105275
138	GSK Investigational Site	Moscow		Russian Federation	129110
139	GSK Investigational Site	N.Novgorod		Russian Federation	603005
140	GSK Investigational Site	Perm		Russian Federation	614088
141	GSK Investigational Site	Ryazan		Russian Federation	390046
142	GSK Investigational Site	Saint-Petersburg		Russian Federation	190103
143	GSK Investigational Site	Saratov		Russian Federation	410009
144	GSK Investigational Site	Toliyatti		Russian Federation	445846
145	GSK Investigational Site	Volgograd		Russian Federation	400040
146	GSK Investigational Site	Bloemfontein		South Africa	9301
147	GSK Investigational Site	Dundee		South Africa	3000
148	GSK Investigational Site	Durban		South Africa	4001
149	GSK Investigational Site	(Móstoles) Madrid		Spain	28935
150	GSK Investigational Site	Alicante		Spain	03010
151	GSK Investigational Site	Badalona		Spain	08916
152	GSK Investigational Site	Barcelona		Spain	08025
153	GSK Investigational Site	Barcelona		Spain	08035
154	GSK Investigational Site	Barcelona		Spain	08036
155	GSK Investigational Site	Cartagena (Murcia)		Spain	30202
156	GSK Investigational Site	Elche (Alicante)		Spain	03202
157	GSK Investigational Site	Granada		Spain	18003
158	GSK Investigational Site	Granada		Spain	18014
159	GSK Investigational Site	Granollers (Barcelona)		Spain	08400
160	GSK Investigational Site	La Coruña		Spain	15006
161	GSK Investigational Site	Madrid		Spain	28006
162	GSK Investigational Site	Madrid		Spain	28029
163	GSK Investigational Site	Madrid		Spain	28040
164	GSK Investigational Site	Madrid		Spain	28046
165	GSK Investigational Site	Mataró		Spain	08304
166	GSK Investigational Site	Murcia		Spain	30003
167	GSK Investigational Site	Sabadell (Barcelona)		Spain	08208
168	GSK Investigational Site	San Sebastián		Spain	20014
169	GSK Investigational Site	Sevilla		Spain	41007
170	GSK Investigational Site	Sevilla		Spain	41013
171	GSK Investigational Site	Valencia		Spain	46010
172	GSK Investigational Site	Valencia		Spain	46015
173	GSK Investigational Site	Kaohsiung		Taiwan	813
174	GSK Investigational Site	Kaohsiung		Taiwan	824
175	GSK Investigational Site	Taichung		Taiwan	404
176	GSK Investigational Site	Taichung		Taiwan	406
177	GSK Investigational Site	Taipei		Taiwan	11217
178	GSK Investigational Site	Woolwich, London	London	United Kingdom	SE18 4QH
179	GSK Investigational Site	Crumpsall, Manchester		United Kingdom	M8 5RB
180	GSK Investigational Site	Liverpool		United Kingdom	L7 8XP
181	GSK Investigational Site	Tooting, London		United Kingdom	SW17 0QT

Sponsors and Collaborators

• ViiV Healthcare
• Shionogi
• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, ViiV Healthcare

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF, Richmond G, Buendia CB, Fourie J, Ramgopal M, Hagins D, Felizarta F, Madruga J, Reuter T, Newman T, Small CB, Lombaard J, Grinsztejn B, Dorey D, Underwood M, Griffith S, Min S; extended SAILING Study Team. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013 Aug 24;382(9893):700-8. doi: 10.1016/S0140-6736(13)61221-0. Epub 2013 Jul 3. Erratum in: Lancet. 2014 Jan 4;383(9911):30.

• Responsible Party: ViiV Healthcare
• ClinicalTrials.gov Identifier: NCT01231516
• Other Study ID Numbers: 111762; 2009-018001-51
• First Posted: Nov 1, 2010
• Last Update Posted: Mar 15, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by ViiV Healthcare: ART-experienced; Integrase inhibitor; Raltegravir; GSK1349572; Integrase inhibitor naive
• Additional relevant MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Raltegravir Potassium; Dolutegravir

Study Results

Participant Flow

Recruitment Details	This study was conducted to demonstrate non-inferior antiviral activity of dolutegravir (DTG) 50 milligram (mg) once daily versus raltegravir (RAL) 400 mg twice daily in participants with human immunodeficiency viruses (HIV)-1. Long-term antiviral activity, tolerability & safety were also evaluated
Pre-assignment Detail	1441 participants screened; 724 participants randomized, of which 5 participants did not receive study treatment. 719 participants received at least 1 dose of study medication creating the intent to treat exposed (ITT-E) Population.

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Period Title: Double-blind Phase (Up to Week [Wk] 48)
STARTED	360	364
ITT-E Population	357	362
Modified (m)ITT-E Population	354	361
COMPLETED	299	283
NOT COMPLETED	61	81
Period Title: Double-blind Phase (Up to Week [Wk] 48)
STARTED	295	126
COMPLETED	227	109
NOT COMPLETED	68	17

Baseline Characteristics

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID	Total
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.	Total of all reporting groups
Overall Participants	354	361	715
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	42.6 (10.45)	42.5 (9.81)	42.5 (10.13)
Sex: Female, Male (Count of Participants)
Female	107 30.2%	123 34.1%	230 32.2%
Male	247 69.8%	238 65.9%	485 67.8%
Race/Ethnicity, Customized (Count of Participants)
African American/African Heritage	143 40.4%	160 44.3%	303 42.4%
American Indian or Alaska Native	10 2.8%	17 4.7%	27 3.8%
Asian-Central/South Asian Heritage	2 0.6%	2 0.6%	4 0.6%
Asian-East Asian Heritage	6 1.7%	4 1.1%	10 1.4%
Asian-South East Asian Heritage	1 0.3%	0 0%	1 0.1%
Native Hawaiian or Other Pacific Islander	1 0.3%	0 0%	1 0.1%
White-Arabic/North African Heritage	3 0.8%	3 0.8%	6 0.8%
White-White/Caucasian/European Heritage	175 49.4%	172 47.6%	347 48.5%
Mixed Race	12 3.4%	2 0.6%	14 2%
Unknown	1 0.3%	1 0.3%	2 0.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48
Description	The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 c/mL at Week 48 was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the randomized phase of the study.
Time Frame	At Week 48

Outcome Measure Data

Analysis Population Description

Modified Intent-To-Treat Exposed (mITT-E) Population: All randomized participants who received at least one dose of investigational product (IP) excluding four participants at one site, which was closed due to Good Clinical Practice (GCP) non-compliance issues in another ViiV sponsored trial.

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	354	361
Number [Percentage of participants]	71 20.1%	64 17.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG 50 mg OD, RAL 400 mg BID
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Non-inferiority of DTG 50 mg and RAL at Week 48 can be concluded if the lower bound of a two-sided 95% confidence interval (CI) for the difference in percentages (DTG - RAL) is greater than -12%. If non-inferiority were established, superiority would be tested at the nominal 5% level based on a pre-specified testing procedure.
Statistical Test of Hypothesis	p-Value	0.030
	Comments	P-value is for test of superiority.
	Method	Cochran-Mantel-Haenszel
	Comments	Adjusted difference in proportion which is based on the difference in percentage, adjusted for Baseline (BL) stratification factors.
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	7.4
	Confidence Interval	(2-Sided) 95%; 0.7 to 14.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was adjusted for BL stratification factors: HIV-1 RNA (<=50000 versus [vs]>50000 c/mL), darunavir-ritonavir use without primary protease inhibitor mutations (yes vs no), and phenotypic susceptibility score (2 vs <2) to background regimen.

2. Secondary Outcome

Title	Number of Participants (Par.) With Detectable Virus That Has Genotypic or Phenotypic Evidence of Treatment-emergent Integrase Inhibitor (INI) Resistance at Time of Protocol Defined Virology Failure (PDVF)
Description	For par. meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure and Baseline 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 logarithm to base 10 (log10) copies/mL by Week 16, 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.
Time Frame	Baseline (Day 1) until PDVF (Up to Week 48)

Outcome Measure Data

Analysis Population Description

mITT-E Population

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	354	361
Count of Participants [Participants]	4 1.1%	17 4.7%

3. Secondary Outcome

Title	Number of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24
Description	The number of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 c/mL at Week 24 was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA at Week 24 as nonresponders, as well as participants who switched their concomitant ART prior to Week 24 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA measurement through Week 24 (within window) while the participant was on-treatment. The result below corresponds to the Week 24 interim analysis.
Time Frame	At Week 24

Outcome Measure Data

Analysis Population Description

mITT-E Population

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	354	361
Count of Participants [Participants]	281 79.4%	252 69.8%

4. Secondary Outcome

Title	Number of Participants With Plasma HIV-1 RNA <400 c/mL at Week 24 and Week 48
Description	The number of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <400 c/mL at the visit of interest was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA at the visit of interest as nonresponders, as well as participants who switched their concomitant ART prior to the visit of interest as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA measurment (within window) for the timepoint of interest while the participant was on-treatment.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT-E Population

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	354	361
Week 24	307 86.7%	287 79.5%
Week 48	278 78.5%	257 71.2%

5. Secondary Outcome

Title	Absolute Values of Cluster of Differentiation 4+ (CD4+) Cell Counts at Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 96 and 144
Description	Blood samples were collected at specified time points to assess CD4+ using flow cytometry. Median and interquartile range are presented. Baseline was the latest pre-dose assessment value (Day 1).
Time Frame	Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 96 and 144

Outcome Measure Data

Analysis Population Description

mITT-E Population. Only those participants with data available at the specified time points were analyzed (represented by "n=X" in the category titles).

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	354	361
Baseline (Day 1), n=354, 361	204.5	193.0
Week 4, n=341, 351	266.0	253.0
Week 8, n=338, 346	280.0	268.0
Week 12, n=335, 345	296.0	289.0
Week 16, n=327, 338	299.0	293.0
Week 24, n=326, 326	334.5	326.5
Week 32, n=309, 309	332.0	338.0
Week 40, n=299, 292	376.0	349.0
Week 48, n=298, 286	387.0	378.5
Week 96, n=260, 22	436.5	484.5
Week 144, n=192, 18	500.0	535.0

6. Secondary Outcome

Title	Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12,16, 24, 32, 40, 48, 96 and 144
Description	Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline was the latest pre-dose assessment value (Day 1). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Median and interquartile range is presented.
Time Frame	Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 96 and 144

Outcome Measure Data

Analysis Population Description

mITT-E Population Only those participants with data available at the specified data points were assessed (represented by "n=X" in the category titles).

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	354	361
Week 4, n=341, 351	53.0	45.0
Week 8, n=338, 346	60.5	59.0
Week 12, n=335, 345	74.0	75.0
Week 16, n=327, 338	76.0	79.5
Week 24, n=326, 326	99.0	93.0
Week 32, n=309, 309	107.0	116.0
Week 40, n=299, 292	125.0	117.5
Week 48, n=298, 286	144.0	137.0
Week 96, n=260, 22	198.5	270
Week 144, n= 192, 18	243.0	302.5

7. Secondary Outcome

Title	Number of Participants With Post-Baseline HIV-associated Conditions, Excluding Recurrences, and Disease Progressions
Description	Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of following conditions (CON), without any CON listed in Categories B and C: Asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: Symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C:Clinical CON listed in acquired immunodeficiency syndrome (AIDS) surveillance case definition. Indicators of CDP defined as:CDC CAT A at Baseline (BS) to CDC CAT C event (EV); CDC CAT B at BS to CDC CAT C EV; CDC CAT C at BS to new CDC CAT C EV; or CDC CAT A, B, or C at BS to death.
Time Frame	Up to Week 480

Outcome Measure Data

Analysis Population Description

mITT-E Population

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	354	361
Any CAT	32 9%	25 6.9%
CAT B	16 4.5%	14 3.9%
CAT C	12 3.4%	8 2.2%
Death	6 1.7%	4 1.1%
Progression from CAT A to CAT C	2 0.6%	1 0.3%
Progression from CAT B to CAT C	0 0%	1 0.3%
Progression from CAT C to New CAT C	9 2.5%	5 1.4%
Progression from CAT A, B, or C to Death	6 1.7%	4 1.1%

8. Secondary Outcome

Title	Number of Participants With Post-Baseline Emergent Grade 1 to 4 Clinical Chemistry and Hematology Toxicities
Description	All Grade 1 to 4 post-Baseline-emergent chemistry toxicities included alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), asparate aminotransferase (AST), carbon dioxide (CO2) content/bicarbonate, cholesterol, creatine kinase (CK), creatinine, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol calculation, lipase, total bilirubin, and triglycerides. All Grade 1 to 4 post-Baseline-emergent hematology toxities included hemoglobin, platelet count, total neutrophils, and white blood cell count. The Division of AIDS (DAIDS) defined toxicity grades as follows: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening; Grade 5, death. Higher the grade, more severe the symptoms.
Time Frame	From Baseline (Day 1) until Week 48, including participants with post-treatment events occurring after Week 48 for participants not entering the post-Week 48 Open-Label phase of the study

Outcome Measure Data

Analysis Population Description

Safety Population comprised of all participants who received at least one dose of IP (i.e., DTG or RAL)

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	357	362
ALT	47 13.3%	46 12.7%
Albumin	4 1.1%	3 0.8%
ALP	27 7.6%	42 11.6%
AST	49 13.8%	52 14.4%
CO2 content/bicarbonate	97 27.4%	109 30.2%
Cholesterol	99 28%	103 28.5%
CK	28 7.9%	29 8%
Creatinine	18 5.1%	13 3.6%
Hyperglycaemia	71 20.1%	80 22.2%
Hyperkalemia	7 2%	6 1.7%
Hypernatremia	5 1.4%	7 1.9%
Hypoglycaemia	21 5.9%	14 3.9%
Hypokalemia	37 10.5%	41 11.4%
Hyponatremia	76 21.5%	79 21.9%
LDL cholesterol calculation	68 19.2%	82 22.7%
Lipase	63 17.8%	68 18.8%
Total bilirubin	56 15.8%	53 14.7%
Triglycerides	14 4%	24 6.6%
Hemoglobin	19 5.4%	27 7.5%
Platelet count	36 10.2%	32 8.9%
Total neutrophils	49 13.8%	49 13.6%
White Blood Cell count	19 5.4%	29 8%

9. Secondary Outcome

Title	Number of Participants With Post-Baseline Emergent Grade 1 to 4 Clinical Chemistry and Hematology Toxicities
Description	Blood samples were collected for the analysis of clinical chemistry and hematology parameters: Alanine aminotransferase (ALT), albumin, alkaline phosphate (ALP), aspartate aminotransferase (AST), carbon dioxide (CO2) content/bicarbonate, cholesterol, creatine kinase (CK), creatinine, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hypoonatremia, LDL cholesterol, lipase, total bilirubin, triglycerides, hemoglibin, neutrophils, platelets, white blood cells. Any abnormality in clinical chemistry and hematology parameters were evaluated according to the DAIDS toxicity scale From Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening).Higher the grade, more severe the symptoms.
Time Frame	From Week 48 to Week 480

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants who completed Week 48 and continued into open-label phase were included in this analysis.

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	295	126
ALT, Grades 1 to 4	36 10.2%	9 2.5%
ALT, Grades 2 to 4	11 3.1%	3 0.8%
ALT, Grades 3 to 4	4 1.1%	0 0%
Albumin, Grades 1 to 4	3 0.8%	0 0%
Albumin, Grades 2 to 4	3 0.8%	0 0%
Albumin, Grades 3 to 4	0 0%	0 0%
ALP, Grades 1 to 4	20 5.6%	1 0.3%
ALP, Grades 2 to 4	4 1.1%	1 0.3%
ALP, Grades 3 to 4	1 0.3%	1 0.3%
AST, Grades 1 to 4	36 10.2%	8 2.2%
AST, Grades 2 to 4	14 4%	0 0%
AST, Grades 3 to 4	1 0.3%	0 0%
CO2 content/bicarbonate, Grades 1 to 4	100 28.2%	21 5.8%
CO2 content/bicarbonate, Grades 2 to 4	12 3.4%	3 0.8%
CO2 content/bicarbonate, Grades 3 to 4	0 0%	0 0%
Cholesterol, Grades 1 to 4	138 39%	26 7.2%
Cholesterol, Grades 2 to 4	66 18.6%	16 4.4%
Cholesterol, Grades 3 to 4	11 3.1%	3 0.8%
CK, Grades 1 to 4	35 9.9%	4 1.1%
CK, Grades 2 to 4	11 3.1%	1 0.3%
CK, Grades 3 to 4	2 0.6%	1 0.3%
Creatinine, Grades 1 to 4	20 5.6%	2 0.6%
Creatinine, Grades 2 to 4	8 2.3%	2 0.6%
Creatinine, Grades 3 to 4	2 0.6%	1 0.3%
Hyperglycemia, Grades 1 to 4	94 26.6%	10 2.8%
Hyperglycemia, Grades 2 to 4	40 11.3%	6 1.7%
Hyperglycemia, Grades 3 to 4	7 2%	1 0.3%
Hyperkalemia, Grades 1 to 4	9 2.5%	1 0.3%
Hyperkalemia, Grades 2 to 4	4 1.1%	1 0.3%
Hyperkalemia, Grades 3 to 4	2 0.6%	0 0%
Hypernatremia, Grades 1 to 4	7 2%	1 0.3%
Hypernatremia, Grades 2 to 4	1 0.3%	0 0%
Hypernatremia, Grades 3 to 4	0 0%	0 0%
Hypoglycemia, Grades 1 to 4	22 6.2%	4 1.1%
Hypoglycemia, Grades 2 to 4	2 0.6%	1 0.3%
Hypoglycemia, Grades 3 to 4	0 0%	0 0%
Hypokalemia, Grades 1 to 4	29 8.2%	13 3.6%
Hypokalemia, Grades 2 to 4	1 0.3%	1 0.3%
Hypokalemia, Grades 3 to 4	0 0%	0 0%
Hyponatremia, Grades 1 to 4	55 15.5%	15 4.2%
Hyponatremia, Grades 2 to 4	2 0.6%	0 0%
Hyponatremia, Grades 3 to 4	0 0%	0 0%
LDL cholesterol, Grades 1 to 4	107 30.2%	22 6.1%
LDL cholesterol, Grades 2 to 4	46 13%	10 2.8%
LDL cholesterol, Grades 3 to 4	15 4.2%	3 0.8%
Lipase, Grades 1 to 4	67 18.9%	7 1.9%
Lipase, Grades 2 to 4	35 9.9%	3 0.8%
Lipase, Grades 3 to 4	12 3.4%	0 0%
Total bilirubin, Grades 1 to 4	52 14.7%	11 3%
Total bilirubin, Grades 2 to 4	42 11.9%	10 2.8%
Total bilirubin, Grades 3 to 4	18 5.1%	6 1.7%
Triglycerides, Grades 1 to 4	23 6.5%	2 0.6%
Triglycerides, Grades 2 to 4	23 6.5%	2 0.6%
Triglycerides, Grades 3 to 4	11 3.1%	1 0.3%
Hemoglobin, Grades 1 to 4	11 3.1%	6 1.7%
Hemoglobin, Grades 2 to 4	6 1.7%	0 0%
Hemoglobin, Grades 3 to 4	2 0.6%	0 0%
Neutrophils, Grades 1 to 4	37 10.5%	9 2.5%
Neutrophils, Grades 2 to 4	14 4%	4 1.1%
Neutrophils, Grades 3 to 4	7 2%	2 0.6%
Platelets, Grades 1 to 4	22 6.2%	7 1.9%
Platelets, Grades 2 to 4	11 3.1%	1 0.3%
Platelets, Grades 3 to 4	4 1.1%	0 0%
White Blood Cells, Grades 1 to 4	17 4.8%	3 0.8%
White Blood Cells, Grades 2 to 4	7 2%	1 0.3%
White Blood Cells, Grades 3 to 4	0 0%	0 0%

10. Secondary Outcome

Title	DTG PK Parameters Including Maximum Plasma Drug Concentration (Cmax), Minimal Plasma Drug Concentration (Cmin), and Average Plasma Pre-dose Concentration (C0_avg)
Description	Cmax, Cmin and C0_avg were assessed by population pharmacokinetic (PK) modeling using sparse PK samples which were collected as follows: one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 4, one pre-dose sample at Week 24, and one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 48. Cmax, Cmin and C0_avg were estimated and reported here.
Time Frame	Pre-dose and at 1 to 3 hours or 4 to 12 hours post-dose at Week 4; Pre-dose at Week 24; Pre-dose and 1 to 3 hours or 4 to 12 hours post-dose at Week 48

Outcome Measure Data

Analysis Population Description

PK Concentration Population comprised of all participants who received DTG, underwent sparse PK sampling during the study, and provided evaluable DTG plasma concentration data. Only those participants with data available at the specified data points were assessed (represented by "n=X" in the category titles).

Arm/Group Title	DTG 50 mg OD
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.
Measure Participants	342
C0_avg, n=342	0.926 (131)
Cmax, n=340	3.21 (26.7)
Cmin, n=340	0.849 (76.5)

11. Secondary Outcome

Title	DTG PK Parameter Including Pre-dose Concentration (C0)
Description	C0 was assessed by population PK modeling using sparse PK samples which were collected as follows: one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 4, one pre-dose sample at Week 24, and one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 48. DTG predose concentration (C0) at Week 4, Week 24, and Week 48 was estimated and reported here.
Time Frame	Pre-dose at Weeks 4, 24 and 48

Outcome Measure Data

Analysis Population Description

PK Concentration Population comprised of all participants who received DTG, underwent sparse PK sampling during the study, and provided evaluable DTG plasma concentration data. Only those participants with data available at the specified data points were assessed (represented by "n=X" in the category titles).

Arm/Group Title	DTG 50 mg OD
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.
Measure Participants	342
Week 4, n=329	0.786 (143)
Week 24, n=298	0.940 (132)
Week 48, n=276	0.932 (152)

12. Secondary Outcome

Title	DTG PK Parameters Including Area Under the Plasma Concentration-time Curve From Time Zero to Time Tau Over a Dosing Interval at Steady State (AUC[0-tau])
Description	AUC is defined as the area under the DTG concentration-time curve as a measure of drug exposure over time. AUC(0-tau) is defined as the area under the plasma concentration-time curve from time zero to time tau over a dosing interval at steady state, where tau is the length of the dosing interval of DTG. AUC was assessed by population pharmacokinetic (PK) modeling using sparse PK samples which were collected as follows: one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 4, one pre-dose sample at Week 24, and one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 48.
Time Frame	Pre-dose and at 1 to 3 hours or 4 to 12 hours post-dose at Week 4; Pre-dose at Week 24; Pre-dose and 1 to 3 hours or 4 to 12 hours post-dose at Week 48

Outcome Measure Data

Analysis Population Description

PK Concentration Population: all participants who received DTG, underwent sparse PK sampling during the study, and provided evaluable DTG plasma concentration data. Only those participants available at the indicated time points were assessed.

Arm/Group Title	DTG 50 mg OD
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.
Measure Participants	340
Geometric Mean (Geometric Coefficient of Variation) [Micrograms*hour/milliliter (µg*hr/mL)]	44.7 (40.5)

13. Secondary Outcome

Title	Change From Baseline in European Quality of Life-5 Dimensions-3 Levels (EQ-5D-3L) Utility Score
Description	The EQ-5D-3L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 3 levels for each dimension including 1=no problems, 2=some problems, 3=extreme problems. The health state is defined by combining the levels of answers from each of the 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-3L utility score ranges from -0.594 to 1. Higher scores indicate better health. Baseline was the latest pre-dose assessment value (Day 1) and change from Baseline=post-dose value minus Baseline value.
Time Frame	Baseline (Day 1) and at Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

mITT-E Population. Only those participants with data available at the specified data points were assessed (represented by "n=X" in the category titles).

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	354	361
Week 24, n=350, 356	0.010 (0.202)	0.019 (0.204)
Week 48, n=350, 356	0.028 (0.179)	0.013 (0.222)

14. Secondary Outcome

Title	Change From Baseline in European Quality of Life-5 Dimensions-3 Levels (EQ-5D-3L) Thermometer Scores
Description	The EQ-5D-3L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 3 levels for each dimension including 1=no problems, 2=some problems, 3=extreme problems. EQ-5D-3L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Participants were asked to rate their current health status using the visual analogue scale 'Thermometer'. Score ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). Higher scores indicate better heath. Baseline was the latest pre-dose assessment value (Day 1) and change from Baseline=post-dose value minus Baseline value.
Time Frame	Baseline (Day 1) and at Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

mITT-E Population. Only those participants with data available at the specified data points were assessed (represented by "n=X" in the category titles).

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	354	361
Week 24, n=350, 355	6.800 (21.413)	4.645 (18.279)
Week 48, n=350, 355	8.894 (20.356)	5.597 (18.821)

15. Other Pre-specified Outcome

Title	Absolute Values of Cluster of Differentiation 8+ (CD8+) Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Description	The absolute value data for CD8+ cell count was planned to be evaluated. The results for this outcome measure will never be posted.
Time Frame	At Weeks 4, 8, 12, 16, 24, 32, 40, and 48

Outcome Measure Data

Analysis Population Description

mITT-E Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted.

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	0	0

16. Other Pre-specified Outcome

Title	Change From Baseline in CD8+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Description	Change from Baseline data for CD8+ cell count was planned to be evaluated. The results for this outcome measure will never be posted.
Time Frame	Baseline (Day 1); Weeks 4, 8, 12, 16, 24, 32, 40, and 48

Outcome Measure Data

Analysis Population Description

mITT-E Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted.

Arm/Group Title	DTG 50 mg OD	RAL 400 mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GlaxoSmithKline (GSK) continued to supply RAL in the Open-Label Phase until commercially available.
Measure Participants	0	0

Adverse Events

Time Frame	Serious adverse events (SAEs), non-serious AEs and all-cause mortality were collected from the start of study medication to the end of the study (up to Week 480)
Adverse Event Reporting Description	SAEs, non-serious AEs and all-cause mortality were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Arm/Group Title	DTG~50mg QD		RAL~400mg BID
Arm/Group Description	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.		Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GSK continued to supply RAL in the Open-Label Phase until it was commercially available.
All Cause Mortality
	DTG~50mg QD		RAL~400mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/357 (1.7%)		4/362 (1.1%)
Serious Adverse Events
	DTG~50mg QD		RAL~400mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/357 (20.4%)		46/362 (12.7%)
Blood and lymphatic system disorders
Anaemia	1/357 (0.3%)	1	2/362 (0.6%)	2
Coagulation factor deficiency	0/357 (0%)	0	1/362 (0.3%)	1
Disseminated intravascular coagulation	1/357 (0.3%)	1	0/362 (0%)	0
Methaemoglobinaemia	1/357 (0.3%)	1	0/362 (0%)	0
Cardiac disorders
Angina pectoris	2/357 (0.6%)	2	0/362 (0%)	0
Cardiomyopathy	0/357 (0%)	0	1/362 (0.3%)	1
Coronary artery disease	0/357 (0%)	0	1/362 (0.3%)	1
Acute myocardial infarction	1/357 (0.3%)	1	0/362 (0%)	0
Cardiac arrest	1/357 (0.3%)	1	0/362 (0%)	0
Cardiac failure	1/357 (0.3%)	1	0/362 (0%)	0
Myocardial infarction	1/357 (0.3%)	1	0/362 (0%)	0
Eye disorders
Iridocyclitis	0/357 (0%)	0	1/362 (0.3%)	1
Iritis	1/357 (0.3%)	1	0/362 (0%)	0
Gastrointestinal disorders
Pancreatitis	1/357 (0.3%)	1	1/362 (0.3%)	1
Abdominal pain	1/357 (0.3%)	1	0/362 (0%)	0
Anal ulcer	0/357 (0%)	0	1/362 (0.3%)	1
Intestinal obstruction	0/357 (0%)	0	1/362 (0.3%)	1
Oral mucosal blistering	0/357 (0%)	0	1/362 (0.3%)	1
Enterovesical fistula	1/357 (0.3%)	1	0/362 (0%)	0
Pancreatitis relapsing	1/357 (0.3%)	1	0/362 (0%)	0
Rectal haemorrhage	1/357 (0.3%)	1	0/362 (0%)	0
Small intestinal obstruction	0/357 (0%)	0	1/362 (0.3%)	1
Haemorrhoidal haemorrhage	1/357 (0.3%)	1	0/362 (0%)	0
Inguinal hernia	1/357 (0.3%)	1	0/362 (0%)	0
Obstructive pancreatitis	0/357 (0%)	0	1/362 (0.3%)	1
General disorders
Chest pain	1/357 (0.3%)	1	0/362 (0%)	0
Oedema peripheral	1/357 (0.3%)	1	0/362 (0%)	0
Sudden death	1/357 (0.3%)	1	0/362 (0%)	0
Non-cardiac chest pain	1/357 (0.3%)	1	1/362 (0.3%)	1
Pyrexia	1/357 (0.3%)	1	0/362 (0%)	0
Hepatobiliary disorders
Hepatitis	1/357 (0.3%)	1	1/362 (0.3%)	1
Hepatotoxicity	1/357 (0.3%)	1	1/362 (0.3%)	1
Acute hepatic failure	0/357 (0%)	0	1/362 (0.3%)	1
Liver disorder	1/357 (0.3%)	1	0/362 (0%)	0
Immune system disorders
Immune reconstitution inflammatory syndrome	1/357 (0.3%)	1	0/362 (0%)	0
Sarcoidosis	0/357 (0%)	0	1/362 (0.3%)	1
Drug hypersensitivity	1/357 (0.3%)	1	0/362 (0%)	0
Infections and infestations
Pneumonia	7/357 (2%)	8	7/362 (1.9%)	7
Gastroenteritis	0/357 (0%)	0	1/362 (0.3%)	1
Anal abscess	0/357 (0%)	0	1/362 (0.3%)	1
Bronchitis	1/357 (0.3%)	1	0/362 (0%)	0
Cellulitis	1/357 (0.3%)	1	1/362 (0.3%)	1
Cytomegalovirus oesophagitis	0/357 (0%)	0	1/362 (0.3%)	1
Disseminated tuberculosis	0/357 (0%)	0	1/362 (0.3%)	1
Extrapulmonary tuberculosis	0/357 (0%)	0	1/362 (0.3%)	1
Gangrene	0/357 (0%)	0	1/362 (0.3%)	1
Gas gangrene	0/357 (0%)	0	1/362 (0.3%)	1
Gastroenteritis viral	1/357 (0.3%)	1	0/362 (0%)	0
Genital herpes simplex	0/357 (0%)	0	1/362 (0.3%)	1
Histoplasmosis disseminated	1/357 (0.3%)	1	0/362 (0%)	0
Infection	0/357 (0%)	0	1/362 (0.3%)	1
Infective myositis	0/357 (0%)	0	1/362 (0.3%)	1
Intervertebral discitis	0/357 (0%)	0	1/362 (0.3%)	1
Joint abscess	1/357 (0.3%)	1	0/362 (0%)	0
Pneumonia legionella	1/357 (0.3%)	1	0/362 (0%)	0
Lower respiratory tract infection	2/357 (0.6%)	2	0/362 (0%)	0
Orchitis	0/357 (0%)	0	1/362 (0.3%)	1
Parvovirus infection	1/357 (0.3%)	1	0/362 (0%)	0
Pneumonia staphylococcal	0/357 (0%)	0	1/362 (0.3%)	1
Pneumonia viral	1/357 (0.3%)	1	0/362 (0%)	0
Progressive multifocal leukoencephalopathy	0/357 (0%)	0	1/362 (0.3%)	1
Subcutaneous abscess	0/357 (0%)	0	1/362 (0.3%)	1
Cerebral toxoplasmosis	1/357 (0.3%)	1	0/362 (0%)	0
Tuberculosis liver	1/357 (0.3%)	1	0/362 (0%)	0
Wound infection	0/357 (0%)	0	1/362 (0.3%)	1
Wound infection staphylococcal	0/357 (0%)	0	1/362 (0.3%)	1
Gastroenteritis norovirus	1/357 (0.3%)	1	0/362 (0%)	0
Influenza	1/357 (0.3%)	1	0/362 (0%)	0
Hepatitis A	1/357 (0.3%)	1	0/362 (0%)	0
Varicella zoster virus infection	1/357 (0.3%)	1	0/362 (0%)	0
Renal abscess	1/357 (0.3%)	1	0/362 (0%)	0
Pulmonary tuberculosis	0/357 (0%)	0	1/362 (0.3%)	1
Localised infection	1/357 (0.3%)	1	0/362 (0%)	0
Postoperative wound infection	0/357 (0%)	0	2/362 (0.6%)	2
Injury, poisoning and procedural complications
Alcohol poisoning	1/357 (0.3%)	1	0/362 (0%)	0
Fibula fracture	1/357 (0.3%)	1	0/362 (0%)	0
Overdose	1/357 (0.3%)	1	0/362 (0%)	0
Upper limb fracture	1/357 (0.3%)	1	0/362 (0%)	0
Ankle fracture	1/357 (0.3%)	2	0/362 (0%)	0
Back injury	1/357 (0.3%)	1	0/362 (0%)	0
Clavicle fracture	1/357 (0.3%)	1	0/362 (0%)	0
Fall	1/357 (0.3%)	1	0/362 (0%)	0
Open fracture	1/357 (0.3%)	1	0/362 (0%)	0
Uterine perforation	1/357 (0.3%)	1	0/362 (0%)	0
Investigations
Blood alkaline phosphatase increased	0/357 (0%)	0	1/362 (0.3%)	1
Blood creatine phosphokinase increased	1/357 (0.3%)	1	0/362 (0%)	0
Lipase increased	0/357 (0%)	0	1/362 (0.3%)	1
Metabolism and nutrition disorders
Dehydration	1/357 (0.3%)	1	2/362 (0.6%)	2
Hyperglycaemia	0/357 (0%)	0	1/362 (0.3%)	1
Hyperkalaemia	1/357 (0.3%)	1	0/362 (0%)	0
Lactic acidosis	0/357 (0%)	0	1/362 (0.3%)	1
Type 2 diabetes mellitus	1/357 (0.3%)	1	0/362 (0%)	0
Hyponatraemia	0/357 (0%)	0	1/362 (0.3%)	1
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	2/357 (0.6%)	2	0/362 (0%)	0
Arthritis	0/357 (0%)	0	1/362 (0.3%)	1
Intervertebral disc protrusion	0/357 (0%)	0	1/362 (0.3%)	1
Myositis	1/357 (0.3%)	1	0/362 (0%)	0
Lumbar spinal stenosis	0/357 (0%)	0	1/362 (0.3%)	1
Muscular weakness	1/357 (0.3%)	1	0/362 (0%)	0
Musculoskeletal chest pain	1/357 (0.3%)	1	0/362 (0%)	0
Osteonecrosis	1/357 (0.3%)	1	0/362 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric	1/357 (0.3%)	1	0/362 (0%)	0
Cervix carcinoma	1/357 (0.3%)	1	1/362 (0.3%)	1
Immunoblastic lymphoma	0/357 (0%)	0	1/362 (0.3%)	1
Metastatic neoplasm	1/357 (0.3%)	1	0/362 (0%)	0
Vulval neoplasm	0/357 (0%)	0	1/362 (0.3%)	1
Anogenital warts	3/357 (0.8%)	3	0/362 (0%)	0
Anal neoplasm	1/357 (0.3%)	1	0/362 (0%)	0
Diffuse large B-cell lymphoma	1/357 (0.3%)	1	0/362 (0%)	0
Gastrointestinal adenocarcinoma	0/357 (0%)	0	1/362 (0.3%)	1
Hodgkin's disease	1/357 (0.3%)	1	0/362 (0%)	0
Metastases to lymph nodes	1/357 (0.3%)	1	0/362 (0%)	0
Squamous cell carcinoma	1/357 (0.3%)	1	0/362 (0%)	0
Nervous system disorders
Cerebrovascular accident	0/357 (0%)	0	1/362 (0.3%)	1
Cerebrovascular disorder	1/357 (0.3%)	1	0/362 (0%)	0
Headache	0/357 (0%)	0	1/362 (0.3%)	1
Transient ischaemic attack	2/357 (0.6%)	2	0/362 (0%)	0
Lacunar stroke	0/357 (0%)	0	1/362 (0.3%)	1
Lumbar radiculopathy	0/357 (0%)	0	1/362 (0.3%)	1
Radiculopathy	0/357 (0%)	0	1/362 (0.3%)	1
Seizure	1/357 (0.3%)	1	0/362 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/357 (0.3%)	1	0/362 (0%)	0
Psychiatric disorders
Suicidal ideation	4/357 (1.1%)	4	1/362 (0.3%)	1
Alcohol withdrawal syndrome	2/357 (0.6%)	2	0/362 (0%)	0
Depression	2/357 (0.6%)	4	0/362 (0%)	0
Mental status changes	0/357 (0%)	0	1/362 (0.3%)	1
Suicide attempt	2/357 (0.6%)	3	0/362 (0%)	0
Alcohol abuse	1/357 (0.3%)	1	0/362 (0%)	0
Anxiety	0/357 (0%)	0	1/362 (0.3%)	1
Depression suicidal	0/357 (0%)	0	1/362 (0.3%)	1
Substance abuse	0/357 (0%)	0	1/362 (0.3%)	1
Hallucination	1/357 (0.3%)	1	1/362 (0.3%)	1
Renal and urinary disorders
Renal failure	1/357 (0.3%)	1	0/362 (0%)	0
Nephrolithiasis	1/357 (0.3%)	1	0/362 (0%)	0
Acute kidney injury	3/357 (0.8%)	3	1/362 (0.3%)	1
Renal impairment	1/357 (0.3%)	1	0/362 (0%)	0
Reproductive system and breast disorders
Cervical dysplasia	0/357 (0%)	0	1/362 (0.3%)	1
Uterine haemorrhage	0/357 (0%)	0	1/362 (0.3%)	1
Menorrhagia	1/357 (0.3%)	1	0/362 (0%)	0
Respiratory, thoracic and mediastinal disorders
Alveolar proteinosis	0/357 (0%)	0	1/362 (0.3%)	1
Dyspnoea	0/357 (0%)	0	1/362 (0.3%)	1
Epistaxis	0/357 (0%)	0	1/362 (0.3%)	1
Respiratory distress	1/357 (0.3%)	1	0/362 (0%)	0
Sinus disorder	0/357 (0%)	0	1/362 (0.3%)	1
Asthma	1/357 (0.3%)	1	1/362 (0.3%)	1
Pulmonary embolism	1/357 (0.3%)	1	1/362 (0.3%)	2
Nasal valve collapse	1/357 (0.3%)	1	0/362 (0%)	0
Skin and subcutaneous tissue disorders
Rash pruritic	0/357 (0%)	0	1/362 (0.3%)	1
Pruritus	1/357 (0.3%)	1	0/362 (0%)	0
Vascular disorders
Aortic arteriosclerosis	0/357 (0%)	0	1/362 (0.3%)	1
Arteriosclerosis	0/357 (0%)	0	1/362 (0.3%)	1
Hypertension	1/357 (0.3%)	1	1/362 (0.3%)	1
Malignant hypertension	0/357 (0%)	0	1/362 (0.3%)	1
Peripheral artery occlusion	0/357 (0%)	0	1/362 (0.3%)	1
Deep vein thrombosis	1/357 (0.3%)	1	0/362 (0%)	0
Other (Not Including Serious) Adverse Events
	DTG~50mg QD		RAL~400mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	250/357 (70%)		206/362 (56.9%)
Gastrointestinal disorders
Diarrhoea	92/357 (25.8%)	134	64/362 (17.7%)	86
Nausea	35/357 (9.8%)	41	31/362 (8.6%)	38
Vomiting	27/357 (7.6%)	32	20/362 (5.5%)	30
Abdominal pain	21/357 (5.9%)	24	8/362 (2.2%)	8
Abdominal pain upper	23/357 (6.4%)	25	5/362 (1.4%)	5
General disorders
Fatigue	19/357 (5.3%)	21	26/362 (7.2%)	29
Infections and infestations
Upper respiratory tract infection	72/357 (20.2%)	168	37/362 (10.2%)	82
Influenza	42/357 (11.8%)	69	34/362 (9.4%)	50
Nasopharyngitis	43/357 (12%)	67	22/362 (6.1%)	23
Urinary tract infection	35/357 (9.8%)	43	20/362 (5.5%)	24
Sinusitis	31/357 (8.7%)	41	17/362 (4.7%)	20
Bronchitis	27/357 (7.6%)	45	15/362 (4.1%)	18
Gastroenteritis	21/357 (5.9%)	22	7/362 (1.9%)	9
Musculoskeletal and connective tissue disorders
Arthralgia	34/357 (9.5%)	38	27/362 (7.5%)	29
Back pain	30/357 (8.4%)	37	16/362 (4.4%)	17
Pain in extremity	23/357 (6.4%)	25	20/362 (5.5%)	24
Nervous system disorders
Headache	43/357 (12%)	57	36/362 (9.9%)	41
Dizziness	20/357 (5.6%)	21	13/362 (3.6%)	13
Psychiatric disorders
Depression	18/357 (5%)	19	7/362 (1.9%)	7
Respiratory, thoracic and mediastinal disorders
Cough	46/357 (12.9%)	61	26/362 (7.2%)	31
Skin and subcutaneous tissue disorders
Rash	30/357 (8.4%)	34	21/362 (5.8%)	21
Vascular disorders
Hypertension	39/357 (10.9%)	43	15/362 (4.1%)	16

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

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.