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.

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.

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.

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. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

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).

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.

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.

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

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.

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 in 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.

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 28; and Weeks 12, 24, and 48.

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 in the category titles).

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.

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 in the category titles).

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).

ITT-E Population

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).

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

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).

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).

Safety Population

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.

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.

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

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.

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.

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.

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. 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.

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.

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

Safety Population

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.

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

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.

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.

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.

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.

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.

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 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.

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)

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.

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.

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.

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.

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.

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.

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.

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