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

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

Population: 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.

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

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

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

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

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

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

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

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

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

Population: 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).

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

Population: 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.

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

Population: 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).

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)

Population: mITT-E Population

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

Population: mITT-E Population

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

Population: mITT-E Population

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

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

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

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

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

Population: mITT-E Population

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

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

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

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