Regimen Switch to Dolutegravir/Lamivudine Fixed Dose Combination From Current Antiretroviral Regimen in HIV-1 Infected and Virologically Suppressed Adults (SALSA)

• Sponsor: ViiV Healthcare (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04021290
• Collaborator: GlaxoSmithKline (Industry), PPD (Industry)
• Enrollment: 493
• Locations: 119
• Arms: 2
• Anticipated Duration (Months): 32.7
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The aim of this study is to determine if virologically suppressed Human Immunodeficiency Virus (HIV) Type 1 infected adults on a current antiretroviral regimen (CAR) (including 2 nucleoside reverse transcriptase inhibitors [NRTIs] plus a third agent) remain suppressed upon switching to dolutegravir/lamivudine (DTG/3TC) fixed dose combination (FDC). The main objective of the study is to demonstrate the non-inferior antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks in virologically suppressed adults living with HIV-1. The study will also evaluate information regarding the safety and health related quality of life. The study will include Screening Phase (up to 28 days), a Randomization Phase (up to Week 52) and a Continuation Phase (post Week 52). The Continuation Phase is not applicable for participants in Sweden and Denmark. Approximately 490 participants will be randomized in 1:1 ratio to receive DTG/3TC FDC once daily for up to 52 weeks or continue their CAR for 52 weeks. Participants in the DTG/3TC FDC arm who successfully complete up to 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in Continuation Phase.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: DTG/3TC FDC; Drug: CAR	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 493 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a randomized study with parallel group assignment where participants will be randomized into one of the two treatment groups. Participants randomized to DTG/3TC FDC will receive DTG/3TC FDC up to Week 52. Participants randomized to CAR will continue to take their current regimen up to Week 52. Randomization will be stratified by Baseline third agent class (protease inhibitor [PI], integrase inhibitor [INI], or non-nucleoside reverse transcriptase inhibitor [NNRTI]).This is a randomized study with parallel group assignment where participants will be randomized into one of the two treatment groups. Participants randomized to DTG/3TC FDC will receive DTG/3TC FDC up to Week 52. Participants randomized to CAR will continue to take their current regimen up to Week 52. Randomization will be stratified by Baseline third agent class (protease inhibitor [PI], integrase inhibitor [INI], or non-nucleoside reverse transcriptase inhibitor [NNRTI]).
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized, Multicenter, Open-label, Non-inferiority Study Evaluating the Efficacy, Safety and Tolerability of Switching to Dolutegravir/Lamivudine Fixed Dose Combination in HIV-1 Infected Adults Who Are Virologically Suppressed
• Actual Study Start Date: Nov 11, 2019
• Actual Primary Completion Date: Apr 23, 2021
• Anticipated Study Completion Date: Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants receiving DTG/3TC FDC Eligible participants will be randomized to receive 50 milligrams (mg)/300 mg DTG/3TC FDC therapy from Day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Drug: DTG/3TC FDC; DTG/3TC FDC will be available as white, oval, film-coated tablets at a unit dose strength of 50 mg/300 mg. Participants will take DTG/3TC once daily via oral route.
Active Comparator: Participants receiving CAR Eligible participants will continue to receive CAR from Day 1 up to 52 weeks.	Drug: CAR; Participants who are randomized to the CAR arm will continue to take the current treatment until Week 52. CAR will include 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) >=50 Copies/Milliliter (c/mL) as Per Food and Drug Administration (FDA) Snapshot Category at Week 48 [Week 48]

   Number of participants with plasma HIV 1 RNA >=50 c/mL were evaluated using FDA snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA >=50 c/mL were termed as subjects with virologic failure. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.

Secondary Outcome Measures

1. Number of Participants With Plasma HIV-1 RNA <50 c/mL Using the FDA Snapshot Algorithm at Week 48 [Week 48]

   Number of participants with plasma HIV 1 RNA <50 c/mL were evaluated using FDA snapshot algorithm at Week 48 to demonstrate the antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA <50 c/mL were termed as subjects with virologic success. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.

2. Number of Participants With Plasma HIV-1 RNA >=50 c/mL as Per FDA Snapshot Category at Week 24 [Week 24]

   Number of participants with plasma HIV 1 RNA >=50 c/mL were evaluated using FDA snapshot algorithm at Week 24 to demonstrate the antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 24 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA >=50 c/mL were termed as subjects with virologic failure. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.

3. Number of Participants With Plasma HIV-1 RNA <50 c/mL Using the FDA Snapshot Algorithm at Week 24 [Week 24]

   Number of participants with plasma HIV 1 RNA <50 c/mL were evaluated using FDA snapshot algorithm at Week 24 to demonstrate the antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 24 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA <50 c/mL were termed as subjects with virologic success. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.

4. Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count for Week 24 [Baseline (Day 1) and Week 24]

   CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Lymphocyte subsets were collected for assessment of this outcome measure by flow cytometry. Change from Baseline in CD4+ lymphocyte count was assessed at Week 24 to evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR. Plasma samples for lymphocyte subsets were collected.

5. Change From Baseline in CD4+ Cell Count for Week 48 [Baseline (Day 1) and Week 48]

   CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Lymphocyte subsets were collected for assessment of this outcome measure by flow cytometry. Change from Baseline in CD4+ lymphocyte count was assessed at Week 48 to evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR. Plasma samples for lymphocyte subsets were collected.

6. Change From Baseline in CD4+/ Cluster of Differentiation 8 (CD8+) Cell Counts Ratio for Week 24 [Baseline (Day 1) and Week 24]

   CD4+/CD8+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Lymphocyte subsets were collected for assessment of this outcome measure by flow cytometry. Change from Baseline in CD4+/CD8+ lymphocyte cell count ratio was assessed at Week 24 to evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR. Plasma samples for lymphocyte subsets were collected.

7. Change From Baseline in CD4+/CD8+ Cell Counts Ratio for Week 48 [Baseline (Day 1) and Week 48]

   CD4+/CD8+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Lymphocyte subsets were collected for assessment of this outcome measure by flow cytometry. Change from Baseline in CD4+/CD8+ lymphocyte cell count ratio was assessed at Week 48 to evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR. Plasma samples for lymphocyte subsets were collected.

8. Number of Participants With Disease Progression Through Week 24 [Up to Week 24]

   Participants with disease progression included incidences of HIV-associated conditions, Acquired Immuno Deficiency Syndrome (AIDS) and death. HIV-associated conditions were assessed according to the 2014 HIV infection by Centers for Disease Control and Prevention (CDC) classification system for HIV Infection in adults to evaluate the immune effects of DTG /3TC FDC once daily compared to continuation of CAR.

9. Number of Participants With Disease Progression Through Week 48 [Up to Week 48]

   Participants with disease progression included incidences of HIV-associated conditions, AIDS and death. HIV-associated conditions were assessed according to the 2014 HIV infection by CDC classification system for HIV Infection in adults to evaluate the immune effects of DTG /3TC FDC once daily compared to continuation of CAR.

10. Number of Participants With Adverse Events (AEs) and AEs Leading to Discontinuation [Up to Week 52]

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

11. Number of Participants With AEs by Severity Grades [Up to 52 weeks]

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs were evaluated by the investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms

12. Number of Participants With Hepatobiliary Abnormalities Through 52 Weeks [Up to Week 52]

    Blood samples were collected to evaluate hepatobiliary abnormalities. Number of participants with Bilirubin (BIL), Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT)/combination of these with levels more than the defined hepatobiliary abnormality criteria were presented. Hepatocellular injury is defined as ([ALT/ALT ULN]/[ALP/ALP ULN]) >= 5 and ALT >=3xULN.

13. Number of Participants With Any AEs and AEs by Severity Grades for Those Participants With Baseline Creatinine Clearance of 30-49 mL/Min/1.73m^2 [Up to 52 weeks]

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with any AE were presented and AEs were graded according to the DAIDS toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms.

14. Number of Participants With Any AEs and AEs by Severity Grades for Those Participants With Baseline Creatinine Clearance of >=50 mL/Min/1.73m^2 [Up to 52 weeks]

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with any AE were presented and AEs were graded according to the DAIDS toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms.

15. Number of Participants With Any AEs Leading to Discontinuation Based on Baseline Creatinine Clearance of 30-49 mL/Min/1.73m^2 [Up to 52 weeks]

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

16. Number of Participants With Any AEs Leading to Discontinuation Based on Baseline Creatinine Clearance of >=50 mL/Min/1.73m^2 [Up to 52 weeks]

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

17. Number of Participants With Hepatobiliary Abnormalities Through 52 Weeks Based on Baseline Creatinine Clearance of 30-49 mL/Min/1.73m^2 [Up to Week 52]

    Blood samples were collected to evaluate hepatobiliary abnormalities. Number of participants with Bilirubin (BIL), Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT)/combination of these with levels more than the defined hepatobiliary abnormality criteria were presented. Hepatocellular injury is defined as ([ALT/ALT ULN]/[ALP/ALP ULN]) >= 5 and ALT >=3xULN.

18. Number of Participants With Hepatobiliary Abnormalities Through 52 Weeks Based on Baseline Creatinine Clearance of >=50 mL/Min/1.73m^2 [Up to Week 52]

    Blood samples were collected to evaluate hepatobiliary abnormalities. Number of participants with Bilirubin (BIL), Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT)/combination of these with levels more than the defined hepatobiliary abnormality criteria were presented. Hepatocellular injury is defined as ([ALT/ALT ULN]/[ALP/ALP ULN]) >= 5 and ALT >=3xULN.

19. Change From Baseline in Fasting Lipids at Week 24 [Baseline (Day 1) and Week 24]

    Lipid parameters included total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides.

20. Change From Baseline in Fasting Lipids at Week 48 [Baseline (Day 1) and Week 48]

    Lipid parameters included total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides.

21. Number of Participants With Observed Genotypic and Phenotypic Resistance to Antiretrovirals (ARVs) for Participants Meeting Confirmed Virologic Withdrawal (CVW) Criteria [Up to week 48]

    Genotypic and phenotypic testing was conducted for participants who met the CVW criteria, i.e., one assessment with HIV-1 RNA ≥200 c/mL after Day 1 with an immediately prior HIV-1 RNA ≥50 c/mL at any point in the study.

22. Change From Baseline in Health Status by HIV Treatment Satisfaction Questionnaire (TSQ) at Week 24 [Baseline (Day 1) and Week 24]

    The HIV Treatment Satisfaction Questionnaire (HIVTSQ) is a 10-item self-reported scale that consists of a total score ranging from 0 to 60. Higher scores indicate a greater level of patient-reported satisfaction with their current therapy.

23. Change From Baseline in Health Status by HIV TSQ at Week 48 [Baseline (Day 1) and Week 48]

    The HIVTSQ is a 10-item self-reported scale that consists of a total score ranging from 0 to 60. Higher scores indicate a greater level of patient-reported satisfaction with their current therapy.

24. Change From Baseline in Health Status by Symptom Distress Module (SDM) at Week 24 [Baseline (Day 1) and Week 24]

    SDM is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Each item is rated from 0 to 4 where 0 (complete absence of symptom) and 4 (very bothersome symptom). Overall score calculated as the sum of the scores for each of the 20 items of the questionnaire and ranged from 0 (best health) and 80 (worst health).

25. Change From Baseline in Health Status by SDM at Week 48 [Baseline (Day 1) and Week 48]

    SDM is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Each item is rated from 0 to 4 where 0 (complete absence of symptom) and 4 (very bothersome symptom). Overall score calculated as the sum of the scores for each of the 20 items of the questionnaire and ranged from 0 (best health) and 80 (worst health).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Eligible participants must be able to understand and comply with protocol requirements, instructions, and restrictions; participant must be likely to complete the study as planned; participants should be considered appropriate candidates for participation in an investigative clinical trial with oral medication (example given [e.g.] no active problematic substance abuse, acute major organ disease, or potential long-term work assignments out of the country).

• Participant should be aged 18 years or older (or older, if required by local regulatory agencies), at the time of signing the informed consent.

• Participants living with HIV.

• Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening.

• Plasma HIV-1 RNA <50 c/mL at Screening.

• Participant must be on uninterrupted current regimen (either the initial or second Combination antiretroviral therapy [cART] regimen) for at least 3 months prior to Screening.

1. Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability and/or safety concerns or access to medications, or convenience/simplification and must not have been done for suspected or established treatment failure. The following switches, if they are the only switches, would not be considered a change in regimen. a) A switch from a PI boosted with ritonavir (RTV) to the same PI boosted with cobicistat is allowed (and vice versa). b) A switch from 3TC to emtricitabine (FTC) (and vice versa). c) A switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) (and vice versa).

1. Acceptable stable cART regimens prior to Screening include 2 NRTIs plus a) INI (either the initial or second cART regimen) b) NNRTI (either the initial or second cART regimen) c) Boosted PI (or atazanavir [ATV] unboosted) (either the initial or second PI-based cART regimen).

• A male or female participant.

• A female participant is eligible to participate if she is not pregnant [as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at screen and a negative urine hCG test at randomization (a local serum hCG test at randomization is allowed if it can be done, and results obtained, within 24 hours prior to randomization)], not breastfeeding, and at least one of the following conditions applies; not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period from 28 days prior to the first dose of study medication and for at least 2 weeks after the last dose of study medication. All participants in the study should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner; The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

• Participant must be capable of giving signed informed consent.

• Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.

Exclusion Criteria:

• Women who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study.

• Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease except cutaneous Kaposi's sarcoma not requiring systemic therapy. Historical or current CD4 cell counts less than 200 cells per cubic millimeter (mm^3) are not exclusionary.

• Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.

• Participants with unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• Participants with the evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antigen antibody (anti-HBs) and HBV deoxyribonucleic acid (DNA) as follows: Participants positive for HBsAg are excluded; Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded. Participant's positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded. Anti-HBc must be either total anti-HBc or anti-HBc immunoglobulin G (IgG), and not anti-HBc Immunoglobulin M (IgM). Participants with a documented history of chronic HBV and current undetectable HBV DNA while on a TAF/TDF regimen are excluded.

• Participants with anticipated need for any hepatitis C virus (HCV) therapy during the randomized phase of the study, or anticipated need for HCV therapy with a potential for adverse drug-drug interactions with DTG or 3TC.

• Participants with untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment). Participants who are at least 7 days post completed treatment are eligible.

• Participants with history or presence of allergy intolerance to the study interventions or their components or drugs of their class.

• Participants with ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia.

• Participants who in the investigator's judgment, poses a significant suicidality risk.

• Participants with any pre-existing physical or mental condition which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.

• Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study interventions or render the participant unable to take oral medication.

• Use of any regimen consisting of single or dual ART (peri-partum treatment with single dose nevirapine is allowed).

• Participants with current use of stavudine, didanosine, or nelfinavir.

• Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.

• Participants receiving treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.

• Participants receiving treatment with any of the following agents within 28 days of Screening like radiation therapy; cytotoxic chemotherapeutic agents; any systemic immune suppressant.

• Participants with exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigational product (IP).

• Any evidence of major NRTI mutation or presence of any DTG resistance-associated mutation in any available prior resistance genotype assay test result, if known.

• Participants with any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities. A single repeat test is allowed during the Screening period to verify a result.

• Participants with alanine aminotransferase (ALT) >= 5 times the upper limit of normal (ULN) or ALT >= 3 times ULN and bilirubin >= 1.5 times ULN (with >35 percent direct bilirubin).

• Participants with creatinine clearance of <30 mL/min/1.73m^{2 via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. Participants with creatinine clearance between 30 to 49 mL/min/1.73 m}2 are eligible after the medical monitor has provided approval after reviewing participant's current ART regimen.

• Participants with any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant'sparticipation in the study of an investigational compound.

• Participants within the 12 month window prior to Screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL.

• Participants within the 12 month window prior to Screening and after confirmed suppression to <50 c/mL, 2 or more consecutive plasma HIV-1 RNA measurements >=50 c/mL. A single plasma HIV-1 RNA measurement >50 c/mL but less than 200 c/mL, with confirmation of return to <50 c/mL is allowed.

• Any history of switch to another regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV-1 RNA >=400 c/mL).

• Participants with any drug holiday during the 6 months prior to Screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns.

• Participants who are currently participating in or anticipate to be selected for any other interventional study after randomization.

• Participants enrolled in France (or in other countries as required by local regulations or Ethics Committee/Institutional Review Board [IRB]) who participated in any study using an investigational drug or vaccine during the previous 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 participate simultaneously in another clinical study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Los Angeles	California	United States	90033
2	GSK Investigational Site	Newport Beach	California	United States	92663
3	GSK Investigational Site	San Francisco	California	United States	94110
4	GSK Investigational Site	New Haven	Connecticut	United States	06510
5	GSK Investigational Site	Washington	District of Columbia	United States	20007
6	GSK Investigational Site	Washington	District of Columbia	United States	20017
7	GSK Investigational Site	Pensacola	Florida	United States	32503
8	GSK Investigational Site	West Palm Beach	Florida	United States	33407
9	GSK Investigational Site	Atlanta	Georgia	United States	30309
10	GSK Investigational Site	Savannah	Georgia	United States	31401
11	GSK Investigational Site	Kansas City	Kansas	United States	66160
12	GSK Investigational Site	Saint Louis	Missouri	United States	63108
13	GSK Investigational Site	Hillsborough	New Jersey	United States	08844
14	GSK Investigational Site	Tulsa	Oklahoma	United States	74127
15	GSK Investigational Site	Morgantown	West Virginia	United States	26506
16	GSK Investigational Site	Milwaukee	Wisconsin	United States	53226
17	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1425AWK
18	GSK Investigational Site	Ciudad de Buenos Aires	Buenos Aires	Argentina	C1202ABB
19	GSK Investigational Site	Rosario	Santa Fe	Argentina	S2000PBJ
20	GSK Investigational Site	Buenos Aires		Argentina	1405
21	GSK Investigational Site	Antwerpen		Belgium	2000
22	GSK Investigational Site	Bruxelles		Belgium	1000
23	GSK Investigational Site	Gent		Belgium	9000
24	GSK Investigational Site	Salvador	Bahia	Brazil	40110-060
25	GSK Investigational Site	Curitiba	Paraná	Brazil	80060-900
26	GSK Investigational Site	Campinas	São Paulo	Brazil	13015-080
27	GSK Investigational Site	Manaus		Brazil	69040-000
28	GSK Investigational Site	Rio de Janeiro		Brazil	21040-360
29	GSK Investigational Site	São Paulo		Brazil	01246-090
30	GSK Investigational Site	São Paulo		Brazil	04039-032
31	GSK Investigational Site	Vancouver	British Columbia	Canada	V6Z 2T1
32	GSK Investigational Site	Winnipeg	Manitoba	Canada	R3A 1R9
33	GSK Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
34	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2N2
35	GSK Investigational Site	Montreal	Quebec	Canada	H2L 4E9
36	GSK Investigational Site	Montreal	Quebec	Canada	H4A 3J1
37	GSK Investigational Site	Regina	Saskatchewan	Canada	S4P 0W5
38	GSK Investigational Site	Guangzhou	Guangdong	China	510060
39	GSK Investigational Site	Beijing		China	100015
40	GSK Investigational Site	Beijing		China	100069
41	GSK Investigational Site	Chongqing		China	400000
42	GSK Investigational Site	Shanghai		China	201508
43	GSK Investigational Site	Aarhus		Denmark	8200
44	GSK Investigational Site	Hvidovre		Denmark	2650
45	GSK Investigational Site	Koebenhavn		Denmark	DK-2100
46	GSK Investigational Site	Odense C		Denmark	5000
47	GSK Investigational Site	Bobigny		France	93000
48	GSK Investigational Site	Bordeaux		France	33075
49	GSK Investigational Site	Nice		France	6202
50	GSK Investigational Site	Orléans Cedex 2		France	45067
51	GSK Investigational Site	Paris		France	75010
52	GSK Investigational Site	Paris		France	75012
53	GSK Investigational Site	Toulouse Cedex 9		France	31059
54	GSK Investigational Site	Tourcoing		France	59208
55	GSK Investigational Site	Muenchen	Bayern	Germany	80335
56	GSK Investigational Site	München	Bayern	Germany	81675
57	GSK Investigational Site	Frankfurt	Hessen	Germany	60596
58	GSK Investigational Site	Bonn	Nordrhein-Westfalen	Germany	53105
59	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45122
60	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50668
61	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50674
62	GSK Investigational Site	Hamburg		Germany	20146
63	GSK Investigational Site	Hamburg		Germany	20246
64	GSK Investigational Site	München		Germany	80336
65	GSK Investigational Site	Modena	Emilia-Romagna	Italy	41100
66	GSK Investigational Site	Roma	Lazio	Italy	00149
67	GSK Investigational Site	Roma	Lazio	Italy	00168
68	GSK Investigational Site	Milano	Lombardia	Italy	20127
69	GSK Investigational Site	Milano	Lombardia	Italy	20142
70	GSK Investigational Site	Milano	Lombardia	Italy	20157
71	GSK Investigational Site	Pavia	Lombardia	Italy	27100
72	GSK Investigational Site	Bergamo		Italy	24128
73	GSK Investigational Site	Brescia		Italy	25123
74	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44160
75	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44280
76	GSK Investigational Site	Zapopan	Jalisco	Mexico	45170
77	GSK Investigational Site	Distrito Federal		Mexico	06470
78	GSK Investigational Site	Ekaterinburg		Russian Federation	620149
79	GSK Investigational Site	St. Petersburg		Russian Federation	196645
80	GSK Investigational Site	Tolyatti		Russian Federation	445846
81	GSK Investigational Site	Bloemfontein		South Africa	9301
82	GSK Investigational Site	Cape Town		South Africa	7505
83	GSK Investigational Site	Observatory, Cape Town		South Africa	7925
84	GSK Investigational Site	Badalona, Barcelona		Spain	8916
85	GSK Investigational Site	Cadiz		Spain	11009
86	GSK Investigational Site	Granada		Spain	18016
87	GSK Investigational Site	La Coruña		Spain	15006
88	GSK Investigational Site	Madrid		Spain	28006
89	GSK Investigational Site	Madrid		Spain	28007
90	GSK Investigational Site	Madrid		Spain	28034
91	GSK Investigational Site	Madrid		Spain	28041
92	GSK Investigational Site	Madrid		Spain	28046
93	GSK Investigational Site	Murcia		Spain	30120
94	GSK Investigational Site	Palma de Mallorca		Spain	07198
95	GSK Investigational Site	San Sebastian de los Reyes		Spain	28702
96	GSK Investigational Site	Santa Cruz de Tenerife		Spain	38010
97	GSK Investigational Site	Sevilla		Spain	41013
98	GSK Investigational Site	Valencia		Spain	46014
99	GSK Investigational Site	Göteborg		Sweden	SE-416 85
100	GSK Investigational Site	Malmö		Sweden	SE-205 02
101	GSK Investigational Site	Stockholm		Sweden	SE-118 83
102	GSK Investigational Site	Stockholm		Sweden	SE-14186
103	GSK Investigational Site	Kaohsiumg		Taiwan	81362
104	GSK Investigational Site	Kaohsiung		Taiwan	807
105	GSK Investigational Site	New Taipei		Taiwan	220
106	GSK Investigational Site	Taichung		Taiwan	404
107	GSK Investigational Site	Taipei		Taiwan	10016
108	GSK Investigational Site	Taoyuan		Taiwan	330
109	GSK Investigational Site	Leeds	Yorkshire	United Kingdom	LS9 7TF
110	GSK Investigational Site	Birmingham		United Kingdom	B9 5SS
111	GSK Investigational Site	Brighton		United Kingdom	BN2 1ES
112	GSK Investigational Site	Bristol		United Kingdom	BS10 5NB
113	GSK Investigational Site	Liverpool		United Kingdom	L7 8XP
114	GSK Investigational Site	London		United Kingdom	SW10 9TH
115	GSK Investigational Site	London		United Kingdom	WC1E 6LB
116	GSK Investigational Site	Manchester		United Kingdom	M13 0FH
117	GSK Investigational Site	Manchester		United Kingdom	M8 5RB
118	GSK Investigational Site	Newcastle upon Tyne		United Kingdom	NE7 7DN
119	GSK Investigational Site	Sheffield		United Kingdom	S10 2JF

Sponsors and Collaborators

• ViiV Healthcare
• GlaxoSmithKline
• PPD

Investigators

• Study Director: GSK Clinical Trials, ViiV Healthcare

Study Documents (Full-Text)

• Study Protocol - May 5, 2020
• Statistical Analysis Plan - Nov 5, 2020

More Information

Publications

• Llibre JM, Brites C, Cheng CY, Osiyemi O, Galera C, Hocqueloux L, Maggiolo F, Degen O, Taylor S, Blair E, Man C, Wynne B, Oyee J, Underwood M, Curtis L, Bontempo G, van Wyk J. Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With HIV-1: Week 48 Results From the Phase 3, Non-inferiority SALSA Randomized Trial. Clin Infect Dis. 2022 Mar 2. pii: ciac130. doi: 10.1093/cid/ciac130. [Epub ahead of print]

• Responsible Party: ViiV Healthcare
• ClinicalTrials.gov Identifier: NCT04021290
• Other Study ID Numbers: 208090
• First Posted: Jul 16, 2019
• Last Update Posted: Jul 1, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by ViiV Healthcare: Current antiretroviral regimen (CAR); HIV-1; Long-term antiviral activity; Dolutegravir/lamivudine; Fixed dose combination
• Additional relevant MeSH terms: HIV Infections

Study Results

Participant Flow

Recruitment Details	The results presented are based on the primary analysis. Participants in the DTG/3TC FDC arm will enter the continuation phase (following week 52) for which data collection is still ongoing and additional results will be provided after study completion. However, participants in the CAR arm have completed the study and no additional results will be available.
Pre-assignment Detail	A total of 493 adult participants were enrolled in this study.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 milligrams (mg)/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 nucleoside reverse transcriptase inhibitors (NTRIs) plus either an integrase inhibitor (INI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or boosted protease inhibitor (PI) or atazanavir unboosted.
Period Title: Overall Study
STARTED	246	247
COMPLETED	143	229
NOT COMPLETED	103	18

Baseline Characteristics

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR	Total
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.	Total of all reporting groups
Overall Participants	246	247	493
Age (YEARS) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [YEARS]	45.5 (11.04)	45.8 (11.99)	45.7 (11.51)
Sex: Female, Male (Count of Participants)
Female	108 43.9%	84 34%	192 38.9%
Male	138 56.1%	163 66%	301 61.1%
Race/Ethnicity, Customized (Count of Participants)
African American/African Heritage	45 18.3%	48 19.4%	93 18.9%
American Indian OR Alaska Native	18 7.3%	14 5.7%	32 6.5%
Asian - East Asian Heritage	27 11%	36 14.6%	63 12.8%
Asian - South East Asian Heritage	4 1.6%	3 1.2%	7 1.4%
White - Arabic/North African Heritage	7 2.8%	4 1.6%	11 2.2%
White - White/Caucasian/European Heritage	142 57.7%	140 56.7%	282 57.2%
Multiple	3 1.2%	2 0.8%	5 1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) >=50 Copies/Milliliter (c/mL) as Per Food and Drug Administration (FDA) Snapshot Category at Week 48
Description	Number of participants with plasma HIV 1 RNA >=50 c/mL were evaluated using FDA snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA >=50 c/mL were termed as subjects with virologic failure. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Intent To Treat-Exposed (ITT-E) population included all randomized participants who received at least one dose of study medication either DTG/3TC or CAR.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	246	247
Count of Participants [Participants]	1 0.4%	3 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants Who Received DTG/3TC FDC, Participants Who Received CAR
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was be concluded if the upper bound of the two-sided 95% confidence interval (CI) for the CMH adjusted difference in the proportion of patients with plasma HIV-1 RNA ≥ 50 c/mL between each treatment group (DTG/3TC - CAR) is less than 5%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Percent (ADP)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -2.4 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	ADP was based on Cochran-Mantel Haenszel stratified analysis adjusting for Baseline stratification factor:Baseline third agent (protease inhibitor [PI], non-nucleoside reverse transcriptase inhibitor [NNRTI], and integrase inhibitor [INI]).

2. Secondary Outcome

Title	Number of Participants With Plasma HIV-1 RNA <50 c/mL Using the FDA Snapshot Algorithm at Week 48
Description	Number of participants with plasma HIV 1 RNA <50 c/mL were evaluated using FDA snapshot algorithm at Week 48 to demonstrate the antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA <50 c/mL were termed as subjects with virologic success. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Intent To Treat-Exposed

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	246	247
Count of Participants [Participants]	232 94.3%	229 92.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants Who Received DTG/3TC FDC, Participants Who Received CAR
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority will be concluded if the lower bound of a 2-sided 95% confidence interval for the difference in success rates between the two treatment arms (DTG/3TC-CAR) is greater than -12%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Percent
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -2.8 to 5.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	ADP was based on Cochran-Mantel Haenszel stratified analysis adjusting for Baseline stratification factor:Baseline third agent (PI, NNRTI, and INI).

3. Secondary Outcome

Title	Number of Participants With Plasma HIV-1 RNA >=50 c/mL as Per FDA Snapshot Category at Week 24
Description	Number of participants with plasma HIV 1 RNA >=50 c/mL were evaluated using FDA snapshot algorithm at Week 24 to demonstrate the antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 24 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA >=50 c/mL were termed as subjects with virologic failure. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Intent To Treat-Exposed

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	246	247
Count of Participants [Participants]	0 0%	1 0.4%

4. Secondary Outcome

Title	Number of Participants With Plasma HIV-1 RNA <50 c/mL Using the FDA Snapshot Algorithm at Week 24
Description	Number of participants with plasma HIV 1 RNA <50 c/mL were evaluated using FDA snapshot algorithm at Week 24 to demonstrate the antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 24 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA <50 c/mL were termed as subjects with virologic success. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Intent To Treat-Exposed

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	246	247
Count of Participants [Participants]	234 95.1%	237 96%

5. Secondary Outcome

Title	Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count for Week 24
Description	CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Lymphocyte subsets were collected for assessment of this outcome measure by flow cytometry. Change from Baseline in CD4+ lymphocyte count was assessed at Week 24 to evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR. Plasma samples for lymphocyte subsets were collected.
Time Frame	Baseline (Day 1) and Week 24

Outcome Measure Data

Analysis Population Description

Intent To Treat-Exposed. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	232	235
Median (Inter-Quartile Range) [cells/cubic millimeter (cells/mm^3)]	30.5	10

6. Secondary Outcome

Title	Change From Baseline in CD4+ Cell Count for Week 48
Description	CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Lymphocyte subsets were collected for assessment of this outcome measure by flow cytometry. Change from Baseline in CD4+ lymphocyte count was assessed at Week 48 to evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR. Plasma samples for lymphocyte subsets were collected.
Time Frame	Baseline (Day 1) and Week 48

Outcome Measure Data

Analysis Population Description

Intent To Treat-Exposed. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	232	227
Median (Inter-Quartile Range) [cells/mm^3]	30	2

7. Secondary Outcome

Title	Change From Baseline in CD4+/ Cluster of Differentiation 8 (CD8+) Cell Counts Ratio for Week 24
Description	CD4+/CD8+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Lymphocyte subsets were collected for assessment of this outcome measure by flow cytometry. Change from Baseline in CD4+/CD8+ lymphocyte cell count ratio was assessed at Week 24 to evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR. Plasma samples for lymphocyte subsets were collected.
Time Frame	Baseline (Day 1) and Week 24

Outcome Measure Data

Analysis Population Description

Intent To Treat-Exposed. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	232	235
Median (Inter-Quartile Range) [Ratio]	-0.02	0.01

8. Secondary Outcome

Title	Change From Baseline in CD4+/CD8+ Cell Counts Ratio for Week 48
Description	CD4+/CD8+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Lymphocyte subsets were collected for assessment of this outcome measure by flow cytometry. Change from Baseline in CD4+/CD8+ lymphocyte cell count ratio was assessed at Week 48 to evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR. Plasma samples for lymphocyte subsets were collected.
Time Frame	Baseline (Day 1) and Week 48

Outcome Measure Data

Analysis Population Description

Intent To Treat-Exposed. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	232	227
Median (Inter-Quartile Range) [Ratio]	0.04	0.05

9. Secondary Outcome

Title	Number of Participants With Disease Progression Through Week 24
Description	Participants with disease progression included incidences of HIV-associated conditions, Acquired Immuno Deficiency Syndrome (AIDS) and death. HIV-associated conditions were assessed according to the 2014 HIV infection by Centers for Disease Control and Prevention (CDC) classification system for HIV Infection in adults to evaluate the immune effects of DTG /3TC FDC once daily compared to continuation of CAR.
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

Intent To Treat-Exposed

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	246	247
Count of Participants [Participants]	0 0%	0 0%

10. Secondary Outcome

Title	Number of Participants With Disease Progression Through Week 48
Description	Participants with disease progression included incidences of HIV-associated conditions, AIDS and death. HIV-associated conditions were assessed according to the 2014 HIV infection by CDC classification system for HIV Infection in adults to evaluate the immune effects of DTG /3TC FDC once daily compared to continuation of CAR.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Intent To Treat-Exposed

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	246	247
Count of Participants [Participants]	1 0.4%	0 0%

11. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and AEs Leading to Discontinuation
Description	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least 1 dose of study intervention either DTG/3TC or CAR.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	246	247
AEs	180 73.2%	172 69.6%
AEs leading to discontinuation	5 2%	3 1.2%

12. Secondary Outcome

Title	Number of Participants With AEs by Severity Grades
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs were evaluated by the investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	246	247
Grade 1	92 37.4%	67 27.1%
Grade 2	77 31.3%	86 34.8%
Grade 3	10 4.1%	17 6.9%
Grade 4	0 0%	2 0.8%
Grade 5	1 0.4%	0 0%

13. Secondary Outcome

Title	Number of Participants With Hepatobiliary Abnormalities Through 52 Weeks
Description	Blood samples were collected to evaluate hepatobiliary abnormalities. Number of participants with Bilirubin (BIL), Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT)/combination of these with levels more than the defined hepatobiliary abnormality criteria were presented. Hepatocellular injury is defined as ([ALT/ALT ULN]/[ALP/ALP ULN]) >= 5 and ALT >=3xULN.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	246	247
ALT >=3xUpper Limit of Normal (ULN) & BIL >=2xULN	0 0%	0 0%
ALT >=3xULN & ALP <2xULN & BIL >=2xULN	0 0%	0 0%
ALT >=3xULN & BIL >=1.5xULN	0 0%	0 0%
AST >=3xULN & BIL >=2xULN	0 0%	0 0%
AST >=3xULN & ALP <2xULN & BIL >=2xULN	0 0%	0 0%
AST >=3xULN & BIL >=1.5xULN	0 0%	0 0%
ALT+AST >=20xULN	0 0%	0 0%
ALT+AST >=10xULN	0 0%	0 0%
ALT+AST >=5xULN	0 0%	0 0%
ALT+AST >=3xULN	3 1.2%	2 0.8%
ALT >=20xULN	0 0%	0 0%
ALT >=10xULN	0 0%	0 0%
ALT >=5xULN	1 0.4%	1 0.4%
ALT >=3xULN	6 2.4%	5 2%
AST >=20xULN	0 0%	0 0%
AST >=10xULN	0 0%	0 0%
AST >=5xULN	1 0.4%	0 0%
AST >=3xULN	5 2%	2 0.8%
BIL >=2xULN	0 0%	5 2%
BIL >=1.5xULN	0 0%	7 2.8%
ALP >=1.5xULN	4 1.6%	8 3.2%
ALT >=3xULN - <5xULN	5 2%	4 1.6%
ALT >=5xULN - <10xULN	1 0.4%	1 0.4%
ALT >=10xULN - <20xULN	0 0%	0 0%
Hepatocellular injury	5 2%	1 0.4%
Hepatocellular injury and BIL >=2xULN	0 0%	0 0%

14. Secondary Outcome

Title	Number of Participants With Any AEs and AEs by Severity Grades for Those Participants With Baseline Creatinine Clearance of 30-49 mL/Min/1.73m^2
Description	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with any AE were presented and AEs were graded according to the DAIDS toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	1	4
Any Event	1 0.4%	3 1.2%
Grade 1	1 0.4%	1 0.4%
Grade 2	0 0%	2 0.8%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%
Grade 5	0 0%	0 0%

15. Secondary Outcome

Title	Number of Participants With Any AEs and AEs by Severity Grades for Those Participants With Baseline Creatinine Clearance of >=50 mL/Min/1.73m^2
Description	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with any AE were presented and AEs were graded according to the DAIDS toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	245	243
Any Event	179 72.8%	169 68.4%
Grade 1	91 37%	66 26.7%
Grade 2	77 31.3%	84 34%
Grade 3	10 4.1%	17 6.9%
Grade 4	0 0%	2 0.8%
Grade 5	1 0.4%	0 0%

16. Secondary Outcome

Title	Number of Participants With Any AEs Leading to Discontinuation Based on Baseline Creatinine Clearance of 30-49 mL/Min/1.73m^2
Description	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	1	4
Count of Participants [Participants]	0 0%	1 0.4%

17. Secondary Outcome

Title	Number of Participants With Any AEs Leading to Discontinuation Based on Baseline Creatinine Clearance of >=50 mL/Min/1.73m^2
Description	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	245	243
Count of Participants [Participants]	5 2%	2 0.8%

18. Secondary Outcome

Title	Number of Participants With Hepatobiliary Abnormalities Through 52 Weeks Based on Baseline Creatinine Clearance of 30-49 mL/Min/1.73m^2
Description	Blood samples were collected to evaluate hepatobiliary abnormalities. Number of participants with Bilirubin (BIL), Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT)/combination of these with levels more than the defined hepatobiliary abnormality criteria were presented. Hepatocellular injury is defined as ([ALT/ALT ULN]/[ALP/ALP ULN]) >= 5 and ALT >=3xULN.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	1	4
ALT >=3xUpper Limit of Normal (ULN) & BIL >=2xULN	0 0%	0 0%
ALT >=3xULN & ALP <2xULN & BIL >=2xULN	0 0%	0 0%
ALT >=3xULN & BIL >=1.5xULN	0 0%	0 0%
AST >=3xULN & BIL >=2xULN	0 0%	0 0%
AST >=3xULN & ALP <2xULN & BIL >=2xULN	0 0%	0 0%
AST >=3xULN & BIL >=1.5xULN	0 0%	0 0%
ALT+AST >=20xULN	0 0%	0 0%
ALT+AST >=10xULN	0 0%	0 0%
ALT+AST >=5xULN	0 0%	0 0%
ALT+AST >=3xULN	0 0%	0 0%
ALT >=20xULN	0 0%	0 0%
ALT >=10xULN	0 0%	0 0%
ALT >=5xULN	0 0%	0 0%
ALT >=3xULN	0 0%	0 0%
AST >=20xULN	0 0%	0 0%
AST >=10xULN	0 0%	0 0%
AST >=5xULN	0 0%	0 0%
AST >=3xULN	0 0%	0 0%
BIL >=2xULN	0 0%	1 0.4%
BIL >=1.5xULN	0 0%	1 0.4%
ALP >=1.5xULN	0 0%	0 0%
ALT >=3xULN - <5xULN	0 0%	0 0%
ALT >=5xULN - <10xULN	0 0%	0 0%
ALT >=10xULN - <20xULN	0 0%	0 0%
Hepatocellular injury	0 0%	0 0%
Hepatocellular injury and BIL >=2xULN	0 0%	0 0%

19. Secondary Outcome

Title	Number of Participants With Hepatobiliary Abnormalities Through 52 Weeks Based on Baseline Creatinine Clearance of >=50 mL/Min/1.73m^2
Description	Blood samples were collected to evaluate hepatobiliary abnormalities. Number of participants with Bilirubin (BIL), Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT)/combination of these with levels more than the defined hepatobiliary abnormality criteria were presented. Hepatocellular injury is defined as ([ALT/ALT ULN]/[ALP/ALP ULN]) >= 5 and ALT >=3xULN.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	245	243
ALT >=3xUpper Limit of Normal (ULN) & BIL >=2xULN	0 0%	0 0%
ALT >=3xULN & ALP <2xULN & BIL >=2xULN	0 0%	0 0%
ALT >=3xULN & BIL >=1.5xULN	0 0%	0 0%
AST >=3xULN & BIL >=2xULN	0 0%	0 0%
AST >=3xULN & ALP <2xULN & BIL >=2xULN	0 0%	0 0%
AST >=3xULN & BIL >=1.5xULN	0 0%	0 0%
ALT+AST >=20xULN	0 0%	0 0%
ALT+AST >=10xULN	0 0%	0 0%
ALT+AST >=5xULN	0 0%	0 0%
ALT+AST >=3xULN	3 1.2%	2 0.8%
ALT >=20xULN	0 0%	0 0%
ALT >=10xULN	0 0%	0 0%
ALT >=5xULN	1 0.4%	1 0.4%
ALT >=3xULN	6 2.4%	5 2%
AST >=20xULN	0 0%	0 0%
AST >=10xULN	0 0%	0 0%
AST >=5xULN	1 0.4%	0 0%
AST >=3xULN	5 2%	2 0.8%
BIL >=2xULN	0 0%	4 1.6%
BIL >=1.5xULN	0 0%	6 2.4%
ALP >=1.5xULN	4 1.6%	8 3.2%
ALT >=3xULN - <5xULN	5 2%	4 1.6%
ALT >=5xULN - <10xULN	1 0.4%	1 0.4%
ALT >=10xULN - <20xULN	0 0%	0 0%
Hepatocellular injury	5 2%	1 0.4%
Hepatocellular injury and BIL >=2xULN	0 0%	0 0%

20. Secondary Outcome

Title	Change From Baseline in Fasting Lipids at Week 24
Description	Lipid parameters included total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides.
Time Frame	Baseline (Day 1) and Week 24

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specified time points has been analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	191	168
Serum or Plasma Triglycerides (mg/dL)	-4.944 (56.4947)	-3.571 (61.9494)
Serum or Plasma HDL Cholesterol, Direct (mg/dL)	-0.326 (9.1737)	0.585 (8.3277)
Serum or Plasma Cholesterol (mg/dL)	-3.096 (31.6634)	0.058 (25.8019)
Serum or Plasma LDL Cholesterol (Calculated or Direct), (mg/dL)	-1.64 (25.5153)	-0.06 (19.802)

21. Secondary Outcome

Title	Change From Baseline in Fasting Lipids at Week 48
Description	Lipid parameters included total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides.
Time Frame	Baseline (Day 1) and Week 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specified time points has been analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	186	159
Serum or Plasma Triglycerides (mg/dL)	-3.112 (66.9065)	-4.002 (71.0132)
Serum or Plasma HDL Cholesterol, Direct (mg/dL)	-0.809 (10.5651)	0.688 (8.5584)
Serum or Plasma Cholesterol (mg/dL)	0.131 (30.271)	2.668 (27.0351)
Serum or Plasma LDL Cholesterol (Calculated or Direct), (mg/dL)	1.753 (22.8585)	2.734 (20.0256)

22. Secondary Outcome

Title	Number of Participants With Observed Genotypic and Phenotypic Resistance to Antiretrovirals (ARVs) for Participants Meeting Confirmed Virologic Withdrawal (CVW) Criteria
Description	Genotypic and phenotypic testing was conducted for participants who met the CVW criteria, i.e., one assessment with HIV-1 RNA ≥200 c/mL after Day 1 with an immediately prior HIV-1 RNA ≥50 c/mL at any point in the study.
Time Frame	Up to week 48

Outcome Measure Data

Analysis Population Description

Confirmed Virologic Withdrawal (CVW) population. No participants met the CVW criteria over 48 weeks; therefore, the genotypic and phenotypic resistance virologic analyses were not assessed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	0	0

23. Secondary Outcome

Title	Change From Baseline in Health Status by HIV Treatment Satisfaction Questionnaire (TSQ) at Week 24
Description	The HIV Treatment Satisfaction Questionnaire (HIVTSQ) is a 10-item self-reported scale that consists of a total score ranging from 0 to 60. Higher scores indicate a greater level of patient-reported satisfaction with their current therapy.
Time Frame	Baseline (Day 1) and Week 24

Outcome Measure Data

Analysis Population Description

ITT-E. Only those participants with data available at specified time points has been analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	236	240
Mean (Standard Deviation) [Scores on a scale]	2.9 (5.85)	1 (5.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants Who Received DTG/3TC FDC, Participants Who Received CAR
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; 0.7 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Age (continuous), Sex, Race, Baseline Value (continuous), Treatment by Visit interaction, Baseline Value by Visit interaction, with Visit as the repeated factor.

24. Secondary Outcome

Title	Change From Baseline in Health Status by HIV TSQ at Week 48
Description	The HIVTSQ is a 10-item self-reported scale that consists of a total score ranging from 0 to 60. Higher scores indicate a greater level of patient-reported satisfaction with their current therapy.
Time Frame	Baseline (Day 1) and Week 48

Outcome Measure Data

Analysis Population Description

ITT-E. Only those participants with data available at specified time points has been analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	229	229
Mean (Standard Deviation) [Scores on a scale]	2.9 (6)	1 (5.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants Who Received DTG/3TC FDC, Participants Who Received CAR
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; 0.7 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Age (continuous), Sex, Race, Baseline Value (continuous), Treatment by Visit interaction, Baseline Value by Visit interaction, with Visit as the repeated factor.

25. Secondary Outcome

Title	Change From Baseline in Health Status by Symptom Distress Module (SDM) at Week 24
Description	SDM is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Each item is rated from 0 to 4 where 0 (complete absence of symptom) and 4 (very bothersome symptom). Overall score calculated as the sum of the scores for each of the 20 items of the questionnaire and ranged from 0 (best health) and 80 (worst health).
Time Frame	Baseline (Day 1) and Week 24

Outcome Measure Data

Analysis Population Description

ITT-E. Only those participants with data available at specified time points has been analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	235	239
Mean (Standard Deviation) [Scores on a scale]	-2.6 (8.69)	-0.7 (8.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants Who Received DTG/3TC FDC, Participants Who Received CAR
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.021
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.9 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Age (continuous), Sex, Race, Baseline Value (continuous), Treatment by Visit interaction, Baseline Value by Visit interaction, with Visit as the repeated factor.

26. Secondary Outcome

Title	Change From Baseline in Health Status by SDM at Week 48
Description	SDM is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Each item is rated from 0 to 4 where 0 (complete absence of symptom) and 4 (very bothersome symptom). Overall score calculated as the sum of the scores for each of the 20 items of the questionnaire and ranged from 0 (best health) and 80 (worst health).
Time Frame	Baseline (Day 1) and Week 48

Outcome Measure Data

Analysis Population Description

ITT-E. Only those participants with data available at specified time points has been analyzed.

Arm/Group Title	Participants Who Received DTG/3TC FDC	Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.	Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
Measure Participants	228	226
Mean (Standard Deviation) [Scores on a scale]	-2.4 (7.64)	-1.5 (7.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants Who Received DTG/3TC FDC, Participants Who Received CAR
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.398
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.8 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Age (continuous), Sex, Race, Baseline Value (continuous), Treatment by Visit interaction, Baseline Value by Visit interaction, with Visit as the repeated factor.

Adverse Events

Time Frame	All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected from Day 1 to week 52
Adverse Event Reporting Description	Safety Population included all randomized participants who received at least 1 dose of study intervention. The results presented are based on the primary analysis. Participants in the DTG/3TC FDC arm will enter the continuation phase (following week 52) for which data collection is still ongoing and additional results will be provided after study completion. However, participants in the CAR arm have completed the study and no additional results will be available.
Arm/Group Title	Participants Who Received DTG/3TC FDC		Participants Who Received CAR
Arm/Group Description	Eligible participants were randomized to receive 50 mg/300 mg DTG/3TC FDC therapy from day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.		Eligible participants received CAR from day 1 up to 52 weeks. CAR included 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.
All Cause Mortality
	Participants Who Received DTG/3TC FDC		Participants Who Received CAR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/246 (0.4%)		0/247 (0%)
Serious Adverse Events
	Participants Who Received DTG/3TC FDC		Participants Who Received CAR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/246 (2.8%)		16/247 (6.5%)
Cardiac disorders
Acute myocardial infarction	0/246 (0%)	0	1/247 (0.4%)	1
Eye disorders
Cataract	1/246 (0.4%)	1	0/247 (0%)	0
General disorders
Death	1/246 (0.4%)	1	0/247 (0%)	0
Infections and infestations
COVID-19	1/246 (0.4%)	1	3/247 (1.2%)	3
Pneumonia bacterial	0/246 (0%)	0	2/247 (0.8%)	2
Anal abscess	1/246 (0.4%)	1	0/247 (0%)	0
Cellulitis	0/246 (0%)	0	1/247 (0.4%)	1
Gastroenteritis	0/246 (0%)	0	1/247 (0.4%)	1
Tracheitis	1/246 (0.4%)	1	0/247 (0%)	0
Injury, poisoning and procedural complications
Hip fracture	0/246 (0%)	0	1/247 (0.4%)	1
Post procedural complication	0/246 (0%)	0	1/247 (0.4%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/246 (0%)	0	1/247 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal stromal tumour	1/246 (0.4%)	1	0/247 (0%)	0
Pituitary tumour benign	0/246 (0%)	0	1/247 (0.4%)	1
Squamous cell carcinoma of the cervix	0/246 (0%)	0	1/247 (0.4%)	1
Nervous system disorders
Depressed level of consciousness	0/246 (0%)	0	1/247 (0.4%)	1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/246 (0.4%)	1	0/247 (0%)	0
Renal and urinary disorders
Renal impairment	0/246 (0%)	0	1/247 (0.4%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/246 (0%)	0	1/247 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/246 (0%)	0	1/247 (0.4%)	1
Vascular disorders
Deep vein thrombosis	0/246 (0%)	0	1/247 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Participants Who Received DTG/3TC FDC		Participants Who Received CAR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	179/246 (72.8%)		169/247 (68.4%)
Blood and lymphatic system disorders
Anaemia	2/246 (0.8%)	2	5/247 (2%)	6
Lymphadenopathy	2/246 (0.8%)	2	0/247 (0%)	0
Neutropenia	1/246 (0.4%)	1	0/247 (0%)	0
Cardiac disorders
Left ventricular hypertrophy	1/246 (0.4%)	1	0/247 (0%)	0
Myocardial ischaemia	1/246 (0.4%)	1	0/247 (0%)	0
Congenital, familial and genetic disorders
Dysplastic naevus syndrome	1/246 (0.4%)	1	0/247 (0%)	0
Ear and labyrinth disorders
Vertigo	3/246 (1.2%)	3	0/247 (0%)	0
Ear pain	2/246 (0.8%)	2	0/247 (0%)	0
Cerumen impaction	0/246 (0%)	0	1/247 (0.4%)	1
Ear discomfort	1/246 (0.4%)	1	0/247 (0%)	0
Ear pruritus	0/246 (0%)	0	1/247 (0.4%)	1
Hypoacusis	1/246 (0.4%)	1	0/247 (0%)	0
Meniere's disease	1/246 (0.4%)	1	0/247 (0%)	0
Tinnitus	1/246 (0.4%)	1	0/247 (0%)	0
Endocrine disorders
Acromegaly	0/246 (0%)	0	1/247 (0.4%)	1
Diabetes insipidus	0/246 (0%)	0	1/247 (0.4%)	1
Hypopituitarism	0/246 (0%)	0	1/247 (0.4%)	1
Secondary adrenocortical insufficiency	0/246 (0%)	0	1/247 (0.4%)	1
Secondary hypothyroidism	0/246 (0%)	0	1/247 (0.4%)	1
Thyroid disorder	1/246 (0.4%)	1	0/247 (0%)	0
Eye disorders
Cataract	2/246 (0.8%)	2	0/247 (0%)	0
Conjunctival haemorrhage	1/246 (0.4%)	1	1/247 (0.4%)	1
Conjunctivitis allergic	1/246 (0.4%)	1	0/247 (0%)	0
Dry eye	0/246 (0%)	0	1/247 (0.4%)	1
Glaucoma	1/246 (0.4%)	1	0/247 (0%)	0
Ocular hypertension	1/246 (0.4%)	1	0/247 (0%)	0
Vision blurred	0/246 (0%)	0	1/247 (0.4%)	2
Visual acuity reduced	1/246 (0.4%)	1	0/247 (0%)	0
Gastrointestinal disorders
Diarrhoea	7/246 (2.8%)	7	8/247 (3.2%)	9
Gastrooesophageal reflux disease	4/246 (1.6%)	4	7/247 (2.8%)	7
Nausea	6/246 (2.4%)	7	4/247 (1.6%)	6
Abdominal distension	4/246 (1.6%)	4	5/247 (2%)	7
Constipation	1/246 (0.4%)	1	6/247 (2.4%)	6
Abdominal pain	4/246 (1.6%)	5	1/247 (0.4%)	1
Abdominal pain upper	3/246 (1.2%)	3	2/247 (0.8%)	3
Dyspepsia	4/246 (1.6%)	4	1/247 (0.4%)	1
Flatulence	3/246 (1.2%)	3	2/247 (0.8%)	2
Toothache	3/246 (1.2%)	3	2/247 (0.8%)	2
Vomiting	3/246 (1.2%)	3	2/247 (0.8%)	2
Abdominal pain lower	2/246 (0.8%)	2	2/247 (0.8%)	2
Gastritis	1/246 (0.4%)	1	3/247 (1.2%)	3
Dental caries	3/246 (1.2%)	3	0/247 (0%)	0
Umbilical hernia	1/246 (0.4%)	1	2/247 (0.8%)	2
Haemorrhoids	1/246 (0.4%)	1	1/247 (0.4%)	1
Abdominal discomfort	0/246 (0%)	0	1/247 (0.4%)	1
Anal fissure	0/246 (0%)	0	1/247 (0.4%)	1
Anogenital dysplasia	0/246 (0%)	0	1/247 (0.4%)	1
Colitis	1/246 (0.4%)	1	0/247 (0%)	0
Colitis ulcerative	0/246 (0%)	0	1/247 (0.4%)	1
Diverticulum intestinal	1/246 (0.4%)	1	0/247 (0%)	0
Duodenitis	0/246 (0%)	0	1/247 (0.4%)	1
Dysphagia	0/246 (0%)	0	1/247 (0.4%)	1
Food poisoning	0/246 (0%)	0	1/247 (0.4%)	1
Frequent bowel movements	0/246 (0%)	0	1/247 (0.4%)	1
Gastric cyst	0/246 (0%)	0	1/247 (0.4%)	1
Gastric dilatation	1/246 (0.4%)	1	0/247 (0%)	0
Gastrointestinal disorder	1/246 (0.4%)	2	0/247 (0%)	0
Gingival pain	0/246 (0%)	0	1/247 (0.4%)	1
Gingival swelling	1/246 (0.4%)	1	0/247 (0%)	0
Hiatus hernia	0/246 (0%)	0	1/247 (0.4%)	1
Inguinal hernia	0/246 (0%)	0	1/247 (0.4%)	1
Irritable bowel syndrome	1/246 (0.4%)	1	0/247 (0%)	0
Lip swelling	1/246 (0.4%)	1	0/247 (0%)	0
General disorders
Pyrexia	6/246 (2.4%)	8	7/247 (2.8%)	7
Fatigue	5/246 (2%)	5	6/247 (2.4%)	6
Chest pain	1/246 (0.4%)	1	3/247 (1.2%)	3
Asthenia	2/246 (0.8%)	2	1/247 (0.4%)	1
Chest discomfort	2/246 (0.8%)	2	1/247 (0.4%)	1
Influenza like illness	2/246 (0.8%)	2	1/247 (0.4%)	1
Feeling abnormal	1/246 (0.4%)	1	1/247 (0.4%)	1
Pain	1/246 (0.4%)	1	1/247 (0.4%)	1
Chills	1/246 (0.4%)	1	0/247 (0%)	0
Cyst	1/246 (0.4%)	1	0/247 (0%)	0
Ill-defined disorder	0/246 (0%)	0	1/247 (0.4%)	1
Malaise	0/246 (0%)	0	1/247 (0.4%)	1
Oedema peripheral	1/246 (0.4%)	2	0/247 (0%)	0
Peripheral swelling	0/246 (0%)	0	1/247 (0.4%)	3
Hepatobiliary disorders
Hepatic steatosis	1/246 (0.4%)	1	1/247 (0.4%)	1
Hyperbilirubinaemia	0/246 (0%)	0	1/247 (0.4%)	1
Immune system disorders
Food allergy	0/246 (0%)	0	1/247 (0.4%)	1
Hypersensitivity	0/246 (0%)	0	1/247 (0.4%)	1
Seasonal allergy	0/246 (0%)	0	1/247 (0.4%)	1
Infections and infestations
Upper respiratory tract infection	11/246 (4.5%)	11	15/247 (6.1%)	16
COVID-19	14/246 (5.7%)	14	8/247 (3.2%)	8
Nasopharyngitis	11/246 (4.5%)	12	9/247 (3.6%)	10
Syphilis	9/246 (3.7%)	10	5/247 (2%)	5
Gastroenteritis	3/246 (1.2%)	3	5/247 (2%)	5
Urinary tract infection	3/246 (1.2%)	4	5/247 (2%)	5
Conjunctivitis	2/246 (0.8%)	2	3/247 (1.2%)	3
Sinusitis	1/246 (0.4%)	1	4/247 (1.6%)	4
Bronchitis	2/246 (0.8%)	2	2/247 (0.8%)	2
Chlamydial infection	2/246 (0.8%)	2	2/247 (0.8%)	3
Influenza	1/246 (0.4%)	1	3/247 (1.2%)	3
Onychomycosis	2/246 (0.8%)	2	2/247 (0.8%)	2
Otitis externa	1/246 (0.4%)	1	3/247 (1.2%)	3
Pharyngitis	2/246 (0.8%)	2	2/247 (0.8%)	2
Proctitis gonococcal	1/246 (0.4%)	1	3/247 (1.2%)	3
Herpes zoster	2/246 (0.8%)	2	1/247 (0.4%)	2
Oropharyngeal gonococcal infection	2/246 (0.8%)	2	1/247 (0.4%)	1
Respiratory tract infection	2/246 (0.8%)	2	1/247 (0.4%)	1
Rhinitis	2/246 (0.8%)	2	1/247 (0.4%)	1
Suspected COVID-19	1/246 (0.4%)	1	2/247 (0.8%)	2
Cellulitis	0/246 (0%)	0	2/247 (0.8%)	2
Cystitis	2/246 (0.8%)	2	0/247 (0%)	0
Ear infection	1/246 (0.4%)	1	1/247 (0.4%)	1
Fungal skin infection	1/246 (0.4%)	1	1/247 (0.4%)	2
Furuncle	1/246 (0.4%)	1	1/247 (0.4%)	1
Gastrointestinal infection	2/246 (0.8%)	2	0/247 (0%)	0
Gonococcal infection	1/246 (0.4%)	2	1/247 (0.4%)	1
Gonorrhoea	1/246 (0.4%)	1	1/247 (0.4%)	1
Herpes simplex	1/246 (0.4%)	2	1/247 (0.4%)	1
Lower respiratory tract infection	1/246 (0.4%)	1	1/247 (0.4%)	1
Oral herpes	2/246 (0.8%)	3	0/247 (0%)	0
Periodontitis	2/246 (0.8%)	2	0/247 (0%)	0
Pharyngotonsillitis	2/246 (0.8%)	2	0/247 (0%)	0
Primary syphilis	0/246 (0%)	0	2/247 (0.8%)	2
Subcutaneous abscess	1/246 (0.4%)	1	1/247 (0.4%)	1
Tonsillitis	0/246 (0%)	0	2/247 (0.8%)	2
Viral infection	1/246 (0.4%)	1	1/247 (0.4%)	1
Acarodermatitis	1/246 (0.4%)	1	0/247 (0%)	0
Anal chlamydia infection	0/246 (0%)	0	1/247 (0.4%)	1
Anorectal human papilloma virus infection	0/246 (0%)	0	1/247 (0.4%)	1
Bacterial vaginosis	1/246 (0.4%)	1	0/247 (0%)	0
Body tinea	1/246 (0.4%)	1	0/247 (0%)	0
Bronchitis viral	1/246 (0.4%)	1	0/247 (0%)	0
Candida infection	1/246 (0.4%)	1	0/247 (0%)	0
Chronic sinusitis	0/246 (0%)	0	1/247 (0.4%)	1
Conjunctivitis bacterial	1/246 (0.4%)	1	0/247 (0%)	0
Eyelid infection	1/246 (0.4%)	1	0/247 (0%)	0
Folliculitis	1/246 (0.4%)	1	0/247 (0%)	0
Fungal infection	0/246 (0%)	0	1/247 (0.4%)	1
Gastroenteritis viral	0/246 (0%)	0	1/247 (0.4%)	2
Genital herpes	1/246 (0.4%)	2	0/247 (0%)	0
Genital herpes simplex	1/246 (0.4%)	2	0/247 (0%)	0
Genitourinary chlamydia infection	1/246 (0.4%)	1	0/247 (0%)	0
Laryngitis	1/246 (0.4%)	1	0/247 (0%)	0
Localised infection	0/246 (0%)	0	1/247 (0.4%)	1
Otitis media acute	0/246 (0%)	0	1/247 (0.4%)	1
Paronychia	0/246 (0%)	0	1/247 (0.4%)	1
Pharyngeal chlamydia infection	1/246 (0.4%)	1	0/247 (0%)	0
Pneumonia bacterial	0/246 (0%)	0	1/247 (0.4%)	1
Pneumonia viral	0/246 (0%)	0	1/247 (0.4%)	1
Secondary syphilis	1/246 (0.4%)	1	0/247 (0%)	0
Sinusitis bacterial	1/246 (0.4%)	1	0/247 (0%)	0
Skin infection	1/246 (0.4%)	1	0/247 (0%)	0
Tinea capitis	1/246 (0.4%)	1	0/247 (0%)	0
Tinea infection	0/246 (0%)	0	1/247 (0.4%)	2
Tinea pedis	1/246 (0.4%)	1	0/247 (0%)	0
Tooth infection	1/246 (0.4%)	2	0/247 (0%)	0
Tracheitis	1/246 (0.4%)	1	0/247 (0%)	0
Urethritis	0/246 (0%)	0	1/247 (0.4%)	1
Urethritis gonococcal	0/246 (0%)	0	1/247 (0.4%)	1
Vulvovaginal candidiasis	1/246 (0.4%)	1	0/247 (0%)	0
Injury, poisoning and procedural complications
Meniscus injury	2/246 (0.8%)	2	1/247 (0.4%)	1
Ankle fracture	0/246 (0%)	0	2/247 (0.8%)	2
Muscle strain	1/246 (0.4%)	1	1/247 (0.4%)	1
Vaccination complication	1/246 (0.4%)	1	1/247 (0.4%)	1
Back injury	0/246 (0%)	0	1/247 (0.4%)	1
Contusion	0/246 (0%)	0	1/247 (0.4%)	1
Dental restoration failure	0/246 (0%)	0	1/247 (0.4%)	1
Face injury	1/246 (0.4%)	1	0/247 (0%)	0
Fall	0/246 (0%)	0	1/247 (0.4%)	1
Foot fracture	0/246 (0%)	0	1/247 (0.4%)	1
Hand fracture	0/246 (0%)	0	1/247 (0.4%)	1
Head injury	0/246 (0%)	0	1/247 (0.4%)	1
Joint dislocation	0/246 (0%)	0	1/247 (0.4%)	1
Joint injury	0/246 (0%)	0	1/247 (0.4%)	1
Ligament sprain	1/246 (0.4%)	1	0/247 (0%)	0
Limb injury	1/246 (0.4%)	1	0/247 (0%)	0
Neck injury	1/246 (0.4%)	1	0/247 (0%)	0
Pelvic organ injury	0/246 (0%)	0	1/247 (0.4%)	1
Penis injury	1/246 (0.4%)	1	0/247 (0%)	0
Post procedural complication	0/246 (0%)	0	1/247 (0.4%)	1
Post-traumatic pain	0/246 (0%)	0	1/247 (0.4%)	1
Road traffic accident	0/246 (0%)	0	1/247 (0.4%)	1
Skin abrasion	0/246 (0%)	0	1/247 (0.4%)	1
Skin injury	0/246 (0%)	0	1/247 (0.4%)	1
Spinal compression fracture	1/246 (0.4%)	1	0/247 (0%)	0
Upper limb fracture	0/246 (0%)	0	1/247 (0.4%)	1
Investigations
Weight increased	20/246 (8.1%)	20	5/247 (2%)	5
Blood creatinine increased	3/246 (1.2%)	3	3/247 (1.2%)	3
Low density lipoprotein increased	2/246 (0.8%)	2	4/247 (1.6%)	4
Blood cholesterol increased	2/246 (0.8%)	2	3/247 (1.2%)	3
Aspartate aminotransferase increased	0/246 (0%)	0	2/247 (0.8%)	2
Blood alkaline phosphatase increased	0/246 (0%)	0	2/247 (0.8%)	2
Blood creatine phosphokinase increased	2/246 (0.8%)	2	0/247 (0%)	0
Blood glucose increased	2/246 (0.8%)	2	0/247 (0%)	0
Blood pressure increased	1/246 (0.4%)	1	1/247 (0.4%)	2
Blood triglycerides increased	1/246 (0.4%)	1	1/247 (0.4%)	1
Creatinine renal clearance increased	0/246 (0%)	0	2/247 (0.8%)	2
Glomerular filtration rate decreased	2/246 (0.8%)	2	0/247 (0%)	0
Platelet count decreased	1/246 (0.4%)	1	1/247 (0.4%)	1
Transaminases increased	0/246 (0%)	0	2/247 (0.8%)	2
Urine protein/creatinine ratio increased	0/246 (0%)	0	2/247 (0.8%)	2
Weight decreased	1/246 (0.4%)	1	1/247 (0.4%)	1
Alanine aminotransferase increased	0/246 (0%)	0	1/247 (0.4%)	1
Blood cholesterol decreased	0/246 (0%)	0	1/247 (0.4%)	1
Blood creatine increased	0/246 (0%)	0	1/247 (0.4%)	1
Blood glucose abnormal	1/246 (0.4%)	1	0/247 (0%)	0
Blood insulin increased	0/246 (0%)	0	1/247 (0.4%)	1
Blood prolactin increased	0/246 (0%)	0	1/247 (0.4%)	1
Blood urine present	0/246 (0%)	0	1/247 (0.4%)	1
Creatinine renal clearance decreased	1/246 (0.4%)	1	0/247 (0%)	0
Crystal urine present	0/246 (0%)	0	1/247 (0.4%)	1
Glucose urine present	0/246 (0%)	0	1/247 (0.4%)	1
Hepatic enzyme increased	0/246 (0%)	0	1/247 (0.4%)	1
Protein urine present	0/246 (0%)	0	1/247 (0.4%)	1
Pulse absent	0/246 (0%)	0	1/247 (0.4%)	1
SARS-CoV-2 test positive	1/246 (0.4%)	1	0/247 (0%)	0
Urine albumin/creatinine ratio increased	0/246 (0%)	0	1/247 (0.4%)	1
Metabolism and nutrition disorders
Hypercholesterolaemia	3/246 (1.2%)	3	3/247 (1.2%)	3
Hypertriglyceridaemia	1/246 (0.4%)	1	5/247 (2%)	5
Hyperglycaemia	2/246 (0.8%)	2	3/247 (1.2%)	3
Hyperlipidaemia	4/246 (1.6%)	4	1/247 (0.4%)	1
Dyslipidaemia	0/246 (0%)	0	4/247 (1.6%)	4
Decreased appetite	3/246 (1.2%)	3	0/247 (0%)	0
Glucose tolerance impaired	1/246 (0.4%)	1	2/247 (0.8%)	2
Insulin resistance	0/246 (0%)	0	3/247 (1.2%)	3
Vitamin D deficiency	1/246 (0.4%)	1	2/247 (0.8%)	2
Abnormal loss of weight	0/246 (0%)	0	2/247 (0.8%)	2
Diabetes mellitus	1/246 (0.4%)	1	1/247 (0.4%)	1
Hypokalaemia	0/246 (0%)	0	2/247 (0.8%)	2
Increased appetite	2/246 (0.8%)	2	0/247 (0%)	0
Metabolic syndrome	2/246 (0.8%)	2	0/247 (0%)	0
Type 2 diabetes mellitus	2/246 (0.8%)	2	0/247 (0%)	0
Dehydration	0/246 (0%)	0	1/247 (0.4%)	1
Hyperuricaemia	0/246 (0%)	0	1/247 (0.4%)	1
Hypoglycaemia	0/246 (0%)	0	1/247 (0.4%)	1
Obesity	1/246 (0.4%)	1	0/247 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	14/246 (5.7%)	15	7/247 (2.8%)	7
Arthralgia	5/246 (2%)	5	10/247 (4%)	11
Neck pain	4/246 (1.6%)	4	4/247 (1.6%)	6
Pain in extremity	5/246 (2%)	5	3/247 (1.2%)	3
Myalgia	5/246 (2%)	5	1/247 (0.4%)	1
Muscle spasms	2/246 (0.8%)	3	2/247 (0.8%)	2
Musculoskeletal chest pain	1/246 (0.4%)	1	1/247 (0.4%)	1
Rotator cuff syndrome	1/246 (0.4%)	1	1/247 (0.4%)	1
Spinal osteoarthritis	1/246 (0.4%)	1	1/247 (0.4%)	2
Bone formation increased	0/246 (0%)	0	1/247 (0.4%)	1
Cervical spinal stenosis	0/246 (0%)	0	1/247 (0.4%)	1
Chondropathy	1/246 (0.4%)	1	0/247 (0%)	0
Finger deformity	1/246 (0.4%)	1	0/247 (0%)	0
Intervertebral disc protrusion	0/246 (0%)	0	1/247 (0.4%)	1
Jaw cyst	0/246 (0%)	0	1/247 (0.4%)	1
Joint effusion	0/246 (0%)	0	1/247 (0.4%)	1
Muscle fatigue	1/246 (0.4%)	1	0/247 (0%)	0
Muscle tightness	1/246 (0.4%)	2	0/247 (0%)	0
Muscular weakness	0/246 (0%)	0	1/247 (0.4%)	1
Musculoskeletal discomfort	1/246 (0.4%)	1	0/247 (0%)	0
Musculoskeletal pain	0/246 (0%)	0	1/247 (0.4%)	1
Musculoskeletal stiffness	1/246 (0.4%)	1	0/247 (0%)	0
Osteoarthritis	1/246 (0.4%)	1	0/247 (0%)	0
Patellofemoral pain syndrome	0/246 (0%)	0	1/247 (0.4%)	1
Rhabdomyolysis	0/246 (0%)	0	1/247 (0.4%)	1
Tendon pain	1/246 (0.4%)	1	0/247 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm	2/246 (0.8%)	2	0/247 (0%)	0
Basal cell carcinoma	0/246 (0%)	0	1/247 (0.4%)	1
Colon adenoma	1/246 (0.4%)	1	0/247 (0%)	0
Dysplastic naevus	1/246 (0.4%)	1	0/247 (0%)	0
Fibroadenoma of breast	1/246 (0.4%)	1	0/247 (0%)	0
Hepatic neoplasm	0/246 (0%)	0	1/247 (0.4%)	1
Lipoma	1/246 (0.4%)	1	0/247 (0%)	0
Malignant melanoma	0/246 (0%)	0	1/247 (0.4%)	2
Melanocytic naevus	0/246 (0%)	0	1/247 (0.4%)	1
Seborrhoeic keratosis	0/246 (0%)	0	1/247 (0.4%)	1
Squamous cell carcinoma of skin	0/246 (0%)	0	1/247 (0.4%)	1
Uterine leiomyoma	1/246 (0.4%)	2	0/247 (0%)	0
Nervous system disorders
Headache	16/246 (6.5%)	18	17/247 (6.9%)	20
Dizziness	13/246 (5.3%)	15	6/247 (2.4%)	7
Hypoaesthesia	1/246 (0.4%)	2	2/247 (0.8%)	2
Paraesthesia	1/246 (0.4%)	1	2/247 (0.8%)	2
Sciatica	0/246 (0%)	0	3/247 (1.2%)	3
Memory impairment	2/246 (0.8%)	2	0/247 (0%)	0
Presyncope	1/246 (0.4%)	1	1/247 (0.4%)	1
Sensory loss	0/246 (0%)	0	2/247 (0.8%)	2
Syncope	0/246 (0%)	0	2/247 (0.8%)	2
Ageusia	0/246 (0%)	0	1/247 (0.4%)	1
Anosmia	0/246 (0%)	0	1/247 (0.4%)	1
Burning sensation	1/246 (0.4%)	1	0/247 (0%)	0
Carpal tunnel syndrome	1/246 (0.4%)	1	0/247 (0%)	0
Cervical radiculopathy	0/246 (0%)	0	1/247 (0.4%)	1
Cervicobrachial syndrome	0/246 (0%)	0	1/247 (0.4%)	1
Dysgeusia	0/246 (0%)	0	1/247 (0.4%)	1
Hemianopia heteronymous	0/246 (0%)	0	1/247 (0.4%)	1
Hemiparesis	0/246 (0%)	0	1/247 (0.4%)	1
Migraine	1/246 (0.4%)	1	0/247 (0%)	0
Nerve compression	1/246 (0.4%)	1	0/247 (0%)	0
Neuralgia	1/246 (0.4%)	1	0/247 (0%)	0
Tremor	0/246 (0%)	0	1/247 (0.4%)	1
Psychiatric disorders
Insomnia	14/246 (5.7%)	15	4/247 (1.6%)	4
Anxiety	5/246 (2%)	5	6/247 (2.4%)	6
Sleep disorder	3/246 (1.2%)	3	3/247 (1.2%)	3
Depression	2/246 (0.8%)	2	2/247 (0.8%)	2
Abnormal dreams	1/246 (0.4%)	1	1/247 (0.4%)	1
Loss of libido	2/246 (0.8%)	2	0/247 (0%)	0
Suicidal ideation	0/246 (0%)	0	2/247 (0.8%)	2
Adjustment disorder	0/246 (0%)	0	1/247 (0.4%)	1
Adjustment disorder with depressed mood	1/246 (0.4%)	1	0/247 (0%)	0
Affective disorder	1/246 (0.4%)	1	0/247 (0%)	0
Alcohol abuse	1/246 (0.4%)	1	0/247 (0%)	0
Anxiety disorder	1/246 (0.4%)	1	0/247 (0%)	0
Bipolar disorder	1/246 (0.4%)	1	0/247 (0%)	0
Depressed mood	1/246 (0.4%)	1	0/247 (0%)	0
Initial insomnia	1/246 (0.4%)	1	0/247 (0%)	0
Mixed anxiety and depressive disorder	1/246 (0.4%)	1	0/247 (0%)	0
Nightmare	1/246 (0.4%)	2	0/247 (0%)	0
Stress	0/246 (0%)	0	1/247 (0.4%)	1
Renal and urinary disorders
Renal impairment	4/246 (1.6%)	4	3/247 (1.2%)	3
Haematuria	1/246 (0.4%)	1	2/247 (0.8%)	2
Proteinuria	1/246 (0.4%)	1	1/247 (0.4%)	1
Acute kidney injury	0/246 (0%)	0	1/247 (0.4%)	1
Dysuria	0/246 (0%)	0	1/247 (0.4%)	1
Glycosuria	0/246 (0%)	0	1/247 (0.4%)	1
Nephrolithiasis	1/246 (0.4%)	1	0/247 (0%)	0
Renal colic	1/246 (0.4%)	1	0/247 (0%)	0
Urinary incontinence	1/246 (0.4%)	1	0/247 (0%)	0
Urine odour abnormal	1/246 (0.4%)	1	0/247 (0%)	0
Reproductive system and breast disorders
Erectile dysfunction	3/246 (1.2%)	3	1/247 (0.4%)	1
Vaginal haemorrhage	2/246 (0.8%)	2	0/247 (0%)	0
Amenorrhoea	0/246 (0%)	0	1/247 (0.4%)	1
Atrophic vulvovaginitis	0/246 (0%)	0	1/247 (0.4%)	1
Benign prostatic hyperplasia	0/246 (0%)	0	1/247 (0.4%)	1
Dysmenorrhoea	1/246 (0.4%)	1	0/247 (0%)	0
Menstruation delayed	1/246 (0.4%)	1	0/247 (0%)	0
Pelvic pain	0/246 (0%)	0	1/247 (0.4%)	1
Prostatitis	0/246 (0%)	0	1/247 (0.4%)	1
Pruritus genital	1/246 (0.4%)	1	0/247 (0%)	0
Uterine polyp	1/246 (0.4%)	1	0/247 (0%)	0
Vaginal discharge	1/246 (0.4%)	1	0/247 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	3/246 (1.2%)	3	4/247 (1.6%)	4
Oropharyngeal pain	4/246 (1.6%)	4	2/247 (0.8%)	2
Rhinitis allergic	3/246 (1.2%)	4	1/247 (0.4%)	1
Respiratory disorder	2/246 (0.8%)	2	1/247 (0.4%)	1
Dyspnoea	0/246 (0%)	0	2/247 (0.8%)	2
Productive cough	1/246 (0.4%)	1	1/247 (0.4%)	1
Asthma	1/246 (0.4%)	1	0/247 (0%)	0
Chronic obstructive pulmonary disease	0/246 (0%)	0	1/247 (0.4%)	1
Dry throat	1/246 (0.4%)	1	0/247 (0%)	0
Emphysema	0/246 (0%)	0	1/247 (0.4%)	1
Epistaxis	1/246 (0.4%)	1	0/247 (0%)	0
Hiccups	1/246 (0.4%)	1	0/247 (0%)	0
Nasal congestion	1/246 (0.4%)	1	0/247 (0%)	0
Nasal discomfort	0/246 (0%)	0	1/247 (0.4%)	1
Nasal dryness	0/246 (0%)	0	1/247 (0.4%)	1
Nasal obstruction	0/246 (0%)	0	1/247 (0.4%)	1
Nasal septum deviation	0/246 (0%)	0	1/247 (0.4%)	1
Pharyngeal disorder	0/246 (0%)	0	1/247 (0.4%)	1
Rhinorrhoea	0/246 (0%)	0	1/247 (0.4%)	1
Upper-airway cough syndrome	0/246 (0%)	0	1/247 (0.4%)	1
Skin and subcutaneous tissue disorders
Rash	6/246 (2.4%)	7	1/247 (0.4%)	1
Acne	3/246 (1.2%)	3	2/247 (0.8%)	2
Dermatitis	4/246 (1.6%)	5	1/247 (0.4%)	1
Eczema	1/246 (0.4%)	1	2/247 (0.8%)	3
Alopecia	2/246 (0.8%)	2	0/247 (0%)	0
Dermal cyst	1/246 (0.4%)	1	1/247 (0.4%)	1
Dermatitis allergic	2/246 (0.8%)	2	0/247 (0%)	0
Dry skin	0/246 (0%)	0	2/247 (0.8%)	2
Pruritus	1/246 (0.4%)	1	1/247 (0.4%)	1
Rash papular	1/246 (0.4%)	1	1/247 (0.4%)	1
Skin lesion	0/246 (0%)	0	2/247 (0.8%)	2
Actinic keratosis	0/246 (0%)	0	1/247 (0.4%)	1
Dermatitis atopic	0/246 (0%)	0	1/247 (0.4%)	1
Dermatitis bullous	1/246 (0.4%)	1	0/247 (0%)	0
Dermatitis contact	0/246 (0%)	0	1/247 (0.4%)	1
Dyshidrotic eczema	1/246 (0.4%)	1	0/247 (0%)	0
Erythema	0/246 (0%)	0	1/247 (0.4%)	1
Hyperhidrosis	1/246 (0.4%)	1	0/247 (0%)	0
Lichen planus	1/246 (0.4%)	1	0/247 (0%)	0
Miliaria	0/246 (0%)	0	1/247 (0.4%)	1
Night sweats	0/246 (0%)	0	1/247 (0.4%)	1
Photosensitivity reaction	1/246 (0.4%)	2	0/247 (0%)	0
Pseudofolliculitis	0/246 (0%)	0	1/247 (0.4%)	1
Psoriasis	0/246 (0%)	0	1/247 (0.4%)	1
Rash erythematous	1/246 (0.4%)	1	0/247 (0%)	0
Rash maculo-papular	1/246 (0.4%)	1	0/247 (0%)	0
Rosacea	1/246 (0.4%)	1	0/247 (0%)	0
Skin odour abnormal	1/246 (0.4%)	1	0/247 (0%)	0
Skin plaque	0/246 (0%)	0	1/247 (0.4%)	1
Skin ulcer	0/246 (0%)	0	1/247 (0.4%)	1
Solar dermatitis	0/246 (0%)	0	1/247 (0.4%)	1
Solar lentigo	0/246 (0%)	0	1/247 (0.4%)	1
Social circumstances
Stress at work	0/246 (0%)	0	1/247 (0.4%)	1
Vascular disorders
Hypertension	6/246 (2.4%)	7	7/247 (2.8%)	7
Hot flush	2/246 (0.8%)	2	0/247 (0%)	0
Essential hypertension	0/246 (0%)	0	1/247 (0.4%)	1
Peripheral coldness	0/246 (0%)	0	1/247 (0.4%)	1
Peripheral venous disease	0/246 (0%)	0	1/247 (0.4%)	1
Vasodilatation	1/246 (0.4%)	1	0/247 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

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.