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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03446573




Registration number
NCT03446573
Ethics application status
Date submitted
5/01/2018
Date registered
27/02/2018
Date last updated
19/07/2023

Titles & IDs
Public title
Switch Study to Evaluate Dolutegravir Plus Lamivudine in Virologically Suppressed Human Immunodeficiency Virus Type 1 Positive Adults (TANGO)
Scientific title
A Phase III, Randomized, Multicenter, Parallel-group, Non-inferiority Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Dolutegravir Plus Lamivudine in HIV-1 Infected Adults Who Are Virologically Suppressed
Secondary ID [1] 0 0
2015-004401-17
Secondary ID [2] 0 0
204862
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DTG + 3TC
Treatment: Drugs - TAF based regimen (TBR)

Experimental: DTG + 3TC 50 mg/300 mg - Participants will receive a single tablet of a two-drug regimen of DTG 50 mg + 3TC 300 mg once daily from Day 1 through Week 200 (Early and Late Switch Phase).

Active comparator: TAF based regimen (TBR) - Participants will continue their TBR from Day 1 to Week 148 (Early Switch Phase), and eligible participants will switch to DTG + 3TC once daily from Week 148 to 200 (Late Switch Phase).


Treatment: Drugs: DTG + 3TC
DTG+3TC is supplied as white, oval, film-coated, fixed dose combination tablet. The tablets will be available in packed high density polyethylene (HDPE) bottles with induction seals and child-resistant closures.

Treatment: Drugs: TAF based regimen (TBR)
Participants will continue to receive their TBR.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Virologic Failure Endpoint as Per Food and Drug Administration (FDA) Snapshot Category at Week 48
Assessment method [1] 0 0
Percentage of participants with virologic failure (plasma HIV-1 RNA \>=50 c/mL) was evaluated using FDA snapshot algorithm at Week 48. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest. Intent-to-treat exposed (ITT-E) Population comprises of all randomized participants who received at least one dose of study treatment either DTG + 3TC or TBR. Participants were assessed according to the treatment to which the participant was randomized. Any participant receiving a treatment randomization number was considered to be randomized.
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL as Per Snapshot Algorithm at Week 48
Assessment method [1] 0 0
Percentage of participants with plasma HIV-1 RNA \<50 c/mL (virologic success) was evaluated using FDA snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG +3TC once daily compared to continuation of TBR over 48 weeks. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest.
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Percentage of Participants With Virologic Failure Endpoint as Per FDA Snapshot Category at Week 24
Assessment method [2] 0 0
Percentage of participants with plasma HIV-1 RNA \>=50 c/mL was evaluated using FDA snapshot algorithm at Week 24. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest.
Timepoint [2] 0 0
Week 24
Secondary outcome [3] 0 0
Percentage of Participants With Virologic Failure Endpoint as Per FDA Snapshot Category at Weeks 96, 144
Assessment method [3] 0 0
Percentage of participants with plasma HIV-1 RNA \>=50 c/mL was evaluated using FDA snapshot algorithm at Weeks 96 and 144.
Timepoint [3] 0 0
Weeks 96 and 144
Secondary outcome [4] 0 0
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL as Per Snapshot Algorithm at Week 24
Assessment method [4] 0 0
Percentage of participants with plasma HIV-1 RNA \<50 c/mL was evaluated using FDA snapshot algorithm at Week 24. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. Percentage values are rounded off.
Timepoint [4] 0 0
Week 24
Secondary outcome [5] 0 0
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL as Per Snapshot Algorithm at Weeks 96 and 144
Assessment method [5] 0 0
Percentage of participants with plasma HIV-1 RNA \<50 c/mL was evaluated using FDA snapshot algorithm at Weeks 96 and 144.
Timepoint [5] 0 0
Weeks 96 and 144
Secondary outcome [6] 0 0
Change From Baseline in CD4+ Cell Count at Weeks 24 and 48
Assessment method [6] 0 0
CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. 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. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable.
Timepoint [6] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [7] 0 0
Change From Baseline in CD4+ Cell Count at Weeks 96 and 144
Assessment method [7] 0 0
CD4+ cells are a type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+and evaluated by flow cytometry. 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. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable
Timepoint [7] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [8] 0 0
Change From Baseline in CD4+/CD8+ Cell Count Ratio at Weeks 24 and 48
Assessment method [8] 0 0
Blood samples were collected at specified time points to assess CD4+/CD8+ cell count ratio. It was assessed by flow cyclometry to evaluate the immunologic activity of switching to DTG+3TC once daily compared to continuation of TBR over 48 Weeks. Baseline (Day 1) values were the actual CD4+ cell count ratio values at pre-dose Day 1. Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable .
Timepoint [8] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [9] 0 0
Change From Baseline in CD4+/CD8+ Cell Count Ratio at Weeks 96 and 144
Assessment method [9] 0 0
Blood samples were collected at specified time points to assess CD4+/CD8+ cell count ratio and were evaluated by flow cyclometry to evaluate the immunologic activity of switching to DTG+3TC once daily compared to continuation of TBR over Weeks 96 and 144. Baseline (Day 1) values are the actual CD4+ cell count ratio values at pre-dose Day 1. Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable
Timepoint [9] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [10] 0 0
Number of Participants With Disease Progression at Weeks 24 and 48
Assessment method [10] 0 0
HIV-associated conditions were recorded during the study and were assessed according to the 2014 CDC Classification System for HIV Infection in Adults. CDC classification for HIV were: Stage 1: No AIDS defining condition and CD4+ T-lymphocyte count: \>=500 cells/mcL; Stage 2: No AIDS infection and CD4+ lymphocyte count: 200-499 cell/mcL and Stage 3:Documented AIDS defining condition or CD4+ T-lymphocye count \<200 cells/mcL. Disease progression summarize participants who had HIV infection stage 3 associated conditions or death. Indicators of clinical disease progression were defined as: CDC Category Stage 1 at enrollment to Stage 3 event; CDC Category Stage 2 at enrollment to Stage 3 event; CDC Category Stage 3 at enrollment to New Stage 3 Event; CDC Category Stage 1, 2 or 3 at enrollment to Death.
Timepoint [10] 0 0
At Weeks 24 and 48
Secondary outcome [11] 0 0
Number of Participants With Disease Progression at Weeks 96 and 144
Assessment method [11] 0 0
HIV-associated conditions were recorded during the study and assessed according to the 2014 CDC Classification System for HIV Infection in Adults. CDC classification for HIV is: Stage 1: No AIDS defining condition and CD4+ T-lymphocyte count: \>=500 cells/mcL; Stage 2: No AIDS infection and CD4+ lymphocyte count: 200-499 cell/mcL and Stage 3: Documented AIDS-defining condition or CD4+ T-lymphocye count \<200 cells/mcL. Indicators of clinical disease progression is defined as: CDC Category Stage 1 at enrollment to Stage 3 event; CDC Category Stage 2 at enrollment to Stage 3 event; CDC Category Stage 3 at enrollment to New Stage 3 Event; CDC Category Stage 1, 2 or 3 at enrollment to Death.
Timepoint [11] 0 0
At Weeks 96 and 144
Secondary outcome [12] 0 0
Number of Participants With Any Serious Adverse Events (SAEs) and Common (>=2%) Non-serious Adverse Events (Non-SAEs): Up to Week 48
Assessment method [12] 0 0
An AE is any untoward medical occurrence temporally associated with the use of a study treatment, whether or not considered related to study treatment. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other important medical event as per medical or scientific judgment . Safety Population included all participants who received at least one dose of study treatment either DTG + 3TC or TBR. This population was based on the treatment the participant actually received. Number of participants with any SAE and common (\>=2%) non-SAEs are presented.
Timepoint [12] 0 0
Up to Week 48
Secondary outcome [13] 0 0
Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen With Any SAEs and Common (>=2%) Non-SAEs: Up to Week 48
Assessment method [13] 0 0
An AE is any untoward medical occurrence temporally associated with the use of a study treatment, whether or not considered related to study treatment. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other important medical event as per medical or scientific judgment . Number of TDF-based regimen participants with any SAE and common (\>=2%) non-SAEs are presented.
Timepoint [13] 0 0
Up to Week 48
Secondary outcome [14] 0 0
Number of Participants With Any SAEs and Common (>=2%) Non-SAEs: Up to Week 148
Assessment method [14] 0 0
An AE is any untoward medical occurrence temporally associated with the use of a study treatment, whether or not considered related to study treatment. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other important medical event as per medical or scientific judgment
Timepoint [14] 0 0
Up to Week 148
Secondary outcome [15] 0 0
Number of Participants With AEs by Their Severity Grades: Up to Week 48
Assessment method [15] 0 0
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. Adverse events 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. Number of participants with adverse events by maximum grade have been presented.
Timepoint [15] 0 0
Up to Week 48
Secondary outcome [16] 0 0
Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen With AEs by Their Severity Grades: Up to Week 48
Assessment method [16] 0 0
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. Adverse events were evaluated by the investigator and 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. Number of TDF-based regimen participants with adverse events by maximum grade have been presented.
Timepoint [16] 0 0
Up to Week 48
Secondary outcome [17] 0 0
Number of Participants With AEs by Their Severity Grades: Up to Week 144
Assessment method [17] 0 0
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. Adverse events 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. Number of participants with adverse events by maximum grade have been presented.
Timepoint [17] 0 0
Up to Week 144
Secondary outcome [18] 0 0
Number of Participants Who Discontinued the Treatment Due to AEs: Up to Week 48
Assessment method [18] 0 0
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Number of participants who discontinued the treatment due to adverse events have been presented.
Timepoint [18] 0 0
Up to Week 48
Secondary outcome [19] 0 0
Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen Who Discontinued the Treatment Due to AEs: Up to Week 48
Assessment method [19] 0 0
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Number of participants who discontinued the treatment due to adverse events have been presented.
Timepoint [19] 0 0
Up to Week 48
Secondary outcome [20] 0 0
Number of Participants Who Discontinued the Treatment Due to AEs: Up to Week 144
Assessment method [20] 0 0
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.
Timepoint [20] 0 0
Up to Week 144
Secondary outcome [21] 0 0
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities: Up to Week 48
Assessment method [21] 0 0
Blood samples were collected up to Week 48 for the analysis of hematology parameters-platelet count, neutrophils, hemoglobin and leukocytes. Any abnormality in hematology parameters were evaluated according to the DAIDS toxicity scale from Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent hematology toxicities in any of the hematology parameters have been presented.
Timepoint [21] 0 0
Up to Week 48
Secondary outcome [22] 0 0
Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen With Maximum Post-Baseline Emergent Hematology Toxicities: Up to Week 36
Assessment method [22] 0 0
Blood samples were collected up to the Week 36 visit for the analysis of hematology parameters-platelet count, neutrophils, hemoglobin and leukocytes. Any abnormality in hematology parameters were evaluated according to the DAIDS toxicity scale from Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms. Only those TDF-based regimen participants with maximum post-Baseline emergent hematology toxicities in any of the hematology parameters have been presented.
Timepoint [22] 0 0
Up to Week 36
Secondary outcome [23] 0 0
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities: Up to Week 144
Assessment method [23] 0 0
Blood samples were collected up to Week 144 for the analysis of hematology parameters-platelet count, neutrophils, hemoglobin and leukocytes. Any abnormality in hematology parameters are were evaluated according to the DAIDS toxicity scale from Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms.
Timepoint [23] 0 0
Up to Week 144
Secondary outcome [24] 0 0
Number of Participants With Maximum Post-Baseline Emergent Clinical Chemistry Toxicities: Up to Week 48
Assessment method [24] 0 0
Blood samples were collected up to Week 48 for the analysis of clinical chemistry parameters: alanine aminotransferase (ALT), albumin, alkaline phosphate (ALP), aspartate aminotransferase (AST), bilirubin, carbon dioxide (CO2), cholesterol, creatinine kinase (CK), creatinine, direct bilirubin, glomerular filtration rate (GFR) from creatinine adjusted for body surface area (BSA), GFR from cystatin C adjusted using chronic kidney disease-epidemiology collaboration (CKD-EPI), hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol, phosphate and triglycerides. Any abnormality in clinical chemistry parameters were evaluated according to the DAIDS toxicity scale From Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms.
Timepoint [24] 0 0
Up to Week 48
Secondary outcome [25] 0 0
Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen With Maximum Post-Baseline Emergent Clinical Chemistry Toxicities: Up to Week 36
Assessment method [25] 0 0
samples were collected up to the Week 36 visit for the analysis of clinical chemistry parameters: alanine aminotransferase (ALT), albumin, alkaline phosphate (ALP), aspartate aminotransferase (AST), bilirubin, carbon dioxide (CO2), cholesterol, creatinine kinase (CK), creatinine, direct bilirubin, glomerular filtration rate (GFR) from creatinine adjusted using chronic kidney disease-epidemiology collaboration (CKD-EPI), GFR from cystatin C adjusted using CKD-EPI, hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol, phosphate and triglycerides. Any abnormality in clinical chemistry parameters were evaluated according to the DAIDS toxicity scale From Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms.
Timepoint [25] 0 0
Up to Week 36
Secondary outcome [26] 0 0
Number of Participants With Maximum Post-Baseline Emergent Clinical Chemistry Toxicities: Up to Week 144
Assessment method [26] 0 0
Blood samples were collected up to Week 144 for the analysis of clinical chemistry parameters: ALT, albumin, ALP, AST, bilirubin, CO2, cholesterol, CK, creatinine, direct bilirubin, GFR from creatinine adjusted for BSA, GFR from cystatin C adjusted using CKD-EPI, hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, LDL cholesterol, phosphate triglycerides and lactate dehydrogenase. Any abnormality in clinical chemistry parameters were evaluated according to the DAIDS toxicity scale From Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms.
Timepoint [26] 0 0
Up to Week 144
Secondary outcome [27] 0 0
Change From Baseline in Renal Biomarkers- Urine Albumin/Creatinine (UA/C) Ratio and Urine Protein/Creatinine (UP/C) Ratio at Weeks 24 and 48
Assessment method [27] 0 0
Urine samples were collected at Baseline, Week 24 and Week 48. Baseline is defined as Day 1. Change from Baseline in UA/C was calculated as UA/C ratio at post-Baseline visit minus UA/C ratio calculated at Baseline. Estimated geometric mean adjusted ratio (each visit over Baseline) and 95% CI have been presented. Change from Baseline in UP/C and UA/C was calculated as UP/C and UA/C ratio at post-Baseline visit minus UP/C and UA/C ratio calculated at Baseline, respectively. Estimated geometric mean adjusted ratio (each visit over Baseline) and 95% CI have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [27] 0 0
Baseline (Day 1) and at weeks 24 and 48
Secondary outcome [28] 0 0
Change From Baseline in Renal Biomarkers- UA/C Ratio and UP/C Ratio at Weeks 24 and 48 in Participants Randomized to TBR Receiving TDF-based Regimen
Assessment method [28] 0 0
Urine samples were collected at Baseline, Week 24 and Week 48 to assess renal biomarkers - urine albumin/creatinine ratio and urine protein/creatinine ratio. Baseline was defined as the latest pre-dose assessment value with a non-missing value. (Day 1). Change from Baseline in UA/C was calculated as UA/C ratio at post-Baseline visit minus UA/C ratio calculated at Baseline. Change from Baseline in UP/C was calculated as UP/C ratio at post-Baseline visit minus UP/C ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [28] 0 0
Baseline (Day 1) and at weeks 24 and 48
Secondary outcome [29] 0 0
Change From Baseline in Renal Biomarkers- UA/C Ratio and UP/C Ratio at Weeks 96 and 144
Assessment method [29] 0 0
Urine samples were collected at Baseline, Weeks 96 and 144. Baseline is defined as Day 1. Change from Baseline in UA/C is defined as UA/C ratio at post-Baseline visit minus UA/C ratio at Baseline. Change from Baseline in UP/C and UA/C is defined as UP/C and UA/C ratio at post-Baseline visit minus UP/C and UA/C ratio at Baseline, respectively. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen.
Timepoint [29] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [30] 0 0
Change From Baseline in Renal Biomarkers- Urine Beta-2 Microglobulin/Urine Creatinine Ratio at Weeks 24 and 48
Assessment method [30] 0 0
Urine biomarker samples were collected at Baseline, Weeks 24 and 48 to assess urine beta-2 microglobulin/urine creatinine. Geometric mean ratio (visit divided by Baseline) and 95% CI of geometric mean ratio has been presented. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine beta-2-microglobulin/urine creatinine was calculated as urine beta-2-microglobulin/urine creatinine ratio at post-Baseline visit minus urine beta-2-microglobulin/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [30] 0 0
Baseline (Day 1) and at weeks 24 and 48
Secondary outcome [31] 0 0
Change From Baseline in Renal Biomarkers- Urine Beta-2 Microglobulin/Urine Creatinine Ratio at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen
Assessment method [31] 0 0
Urine biomarker samples were collected to assess urine beta-2 microglobulin/urine creatinine. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine beta-2-microglobulin/urine creatinine was calculated as urine beta-2-microglobulin/urine creatinine ratio at post-Baseline visit minus urine beta-2-microglobulin/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [31] 0 0
Baseline (Day 1) and at weeks 24 and 48
Secondary outcome [32] 0 0
Change From Baseline in Renal Biomarkers- Urine Beta-2 Microglobulin/Urine Creatinine Ratio at Weeks 96 and 144
Assessment method [32] 0 0
Urine biomarker samples were collected at Baseline, Weeks 96 and 144 to assess urine beta-2 microglobulin/urine creatinine. Baseline (Day 1) value is the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine beta-2-microglobulin/urine creatinine is defined as urine beta-2-microglobulin/urine creatinine ratio at post-Baseline visit minus urine beta-2-microglobulin/urine creatinine ratio at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen.
Timepoint [32] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [33] 0 0
Change From Baseline in Renal Biomarkers- Urine Phosphate at Weeks 24 and 48
Assessment method [33] 0 0
Urine biomarker samples were collected at Baseline and at Weeks 24 and 48 to assess urine phosphate. Geometric mean ratio (visit divided by Baseline) and 95% CI of geometric mean ratio has been presented. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine phosphate was calculated as urine phosphate at post-Baseline visit minus urine phosphate calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [33] 0 0
Baseline (Day 1) and at weeks 24 and 48
Secondary outcome [34] 0 0
Change From Baseline in Renal Biomarkers- Urine Phosphate at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen
Assessment method [34] 0 0
Urine biomarker samples were collected to assess urine phosphate. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine phosphate was calculated as urine phosphate at post-Baseline visit minus urine phosphate calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [34] 0 0
Baseline (Day 1) and at weeks 24 and 48
Secondary outcome [35] 0 0
Change From Baseline in Renal Biomarkers- Urine Phosphate at Weeks 96 and 144
Assessment method [35] 0 0
Urine biomarker samples were collected at Baseline, Weeks 96 and 144 to assess urine phosphate. Baseline (Day 1) value is the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine phosphate is defined as urine phosphate at post-Baseline visit minus urine phosphate at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen
Timepoint [35] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [36] 0 0
Change From Baseline in Renal Biomarkers- Urine Retinol Binding Protein 4/Urine Creatinine at Weeks 24 and 48
Assessment method [36] 0 0
Urine biomarker samples were collected at Baseline, Weeks 24 and 48 to assess urine retinol binding protein 4/urine creatinine. Geometric mean ratio (visit divided by Baseline) and 95% CI of geometric mean ratio has been presented. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in Urine retinol binding protein 4/urine creatinine ratio was calculated as Urine retinol binding protein 4/urine creatinine ratio at post-Baseline visit minus Urine retinol binding protein 4/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [36] 0 0
Baseline (Day 1) and at weeks 24 and 48
Secondary outcome [37] 0 0
Change From Baseline in Renal Biomarkers- Urine Retinol Binding Protein 4/Urine Creatinine at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen
Assessment method [37] 0 0
Urine biomarker samples were collected to assess urine retinol binding protein 4/urine creatinine. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine retinol binding protein 4/urine creatinine was calculated as urine retinol binding protein 4/urine creatinine ratio at post-Baseline visit minus urine retinol binding protein 4/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [37] 0 0
Baseline (Day 1) and at weeks 24 and 48
Secondary outcome [38] 0 0
Change From Baseline in Renal Biomarkers- Urine Retinol Binding Protein 4/Urine Creatinine at Weeks 96 and 144
Assessment method [38] 0 0
Urine biomarker samples were collected at Baseline, Weeks 96 and 144 to assess urine retinol binding protein 4/urine creatinine. Baseline (Day 1) value is the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in Urine retinol binding protein 4/urine creatinine ratio is defined as Urine retinol binding protein 4/urine creatinine ratio at post-Baseline visit minus Urine retinol binding protein 4/urine creatinine ratio at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen
Timepoint [38] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [39] 0 0
Change From Baseline in Fasting Lipids at Weeks 24 and 48
Assessment method [39] 0 0
Blood samples were collected at Baseline (Day 1), Week 24 and Week 48 to assess fasting lipids which included plasma cholesterol, plasma LDL cholesterol, plasma high density lipoprotein (HDL) cholesterol and plasma triglycerides. Baseline value was the value from 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. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [39] 0 0
Baseline (Day 1) and at weeks 24 and 48
Secondary outcome [40] 0 0
Change From Baseline in Fasting Lipids at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen
Assessment method [40] 0 0
Blood samples were collected at Baseline (Day 1), weeks 24 and 48 visit (participant withdrew from the study at Week 36) to assess fasting lipids which included plasma cholesterol, plasma LDL cholesterol, plasma HDL cholesterol and plasma triglycerides. Baseline value was the value from 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. Change from Baseline values for fasting lipids in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [40] 0 0
Baseline (Day 1) and at weeks 24 and 48
Secondary outcome [41] 0 0
Change From Baseline in Fasting Lipids at Weeks 96 and 144
Assessment method [41] 0 0
Blood samples were collected at Baseline (Day 1), Weeks 96 and 144 to assess fasting lipids which includes plasma cholesterol, plasma LDL cholesterol, plasma HDL cholesterol and plasma triglycerides. Baseline value is the value from 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. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen.
Timepoint [41] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [42] 0 0
Number of Participants With Genotypic Resistance: Up to Week 48
Assessment method [42] 0 0
Plasma samples were collected for drug resistance testing. Number of participants, who met confirmed virologic withdrawal (CVW) criteria (one plasma HIV-1 RNA \>=200 c/mL after Day 1 with immediate prior HIV RNA \>=50 c/mL), with genotypic resistance to INSTI, nucleoside reverse transcriptase inhibitor (NRTI), NNRTI and PI was summarized.
Timepoint [42] 0 0
Up to Week 48
Secondary outcome [43] 0 0
Number of Participants With Genotypic Resistance: Up to Week 144
Assessment method [43] 0 0
Plasma samples were collected for drug resistance testing. Number of participants, who meet CVW criteria (one plasma HIV-1 RNA \>=200 c/mL after Day 1 with immediate prior HIV RNA \>=50 c/mL), with genotypic resistance to INSTI, NRTI, NNRTI and PI are summarized.
Timepoint [43] 0 0
Up to Week 144
Secondary outcome [44] 0 0
Number of Participants With Phenotypic Resistance: Up to Week 48
Assessment method [44] 0 0
Number of participants, who meet CVW criteria (one plasma HIV-1 RNA \>=200 c/mL after Day 1 with immediate prior HIV RNA \>=50 c/mL), with phenotypic resistance to INSTI, NNRTI,NRTI and PI were summarized. Assessment of antiviral activity of ART using phenotypic test results was interpreted through a proprietary algorithm (from Monogram Biosciences), which provided the overall susceptibility of the drug. Partially sensitive and resistant calls were considered resistant in this analysis. The phenotypic resistance was calculated using binary scoring system, where 0 was considered as sensitive and 1 as resistance. Phenotypic Resistance data for the following INSTI, NNRTI, NRTI and PI drugs in participants Meeting CVW Criteria has been presented.
Timepoint [44] 0 0
Up to Week 48
Secondary outcome [45] 0 0
Number of Participants With Phenotypic Resistance: Up to Week 144
Assessment method [45] 0 0
Number of participants, who meet CVW criteria (one plasma HIV-1 RNA \>=200 c/mL after Day 1 with immediate prior HIV RNA \>=50 c/mL), with phenotypic resistance to INSTI,NNRT,NRTI and PI were summarized. Assessment of antiviral activity of anti-retroviral therapy (ART) using phenotypic test results was interpreted through a proprietary algorithm (from Monogram Biosciences), which provided the overall susceptibility of the drug. Partially sensitive and resistant calls were considered resistant in this analysis. The phenotypic resistance was calculated using binary scoring system, where 0 was considered as sensitive and 1 as resistance. Phenotypic Resistance data for the following INSTI, NNRTI, NRTI and PI drugs in participants Meeting CVW Criteria has been presented.
Timepoint [45] 0 0
Up to Week 144
Secondary outcome [46] 0 0
Change From Baseline in Bone Biomarkers-serum Bone-specific ALP (Bone-ALP), Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Type 1 Collagen C-telopeptides (CTX-1) at Weeks 24 and 48
Assessment method [46] 0 0
Serum samples were collected for analysis of bone biomarkers. Baseline was latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and its corresponding standard error has been presented. Adjusted mean was the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for treatment, visit, Baseline third agent class, CD4+ cell count (continuous), age (continuous), sex, race, body mass index (BMI) (continuous), smoking status, vitamin D use, Baseline biomarker (continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor.One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [46] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [47] 0 0
Change From Baseline in Bone Biomarkers-serum Bone-specific ALP (Bone-ALP), Osteocalcin, Serum P1NP and Serum CTX-1 in Participants Randomized to TBR Arm Receiving TDF-based Regimen at Weeks 24 and 48
Assessment method [47] 0 0
Serum samples were collected for analysis of bone biomarkers. Baseline was latest pre-dose assessment with a non-missing value (Day 1) . Change from Baseline is post-dose visit value minus Baseline value. Change from Baseline in bone biomarkers-serum bone-specific ALP (Bone-ALP), osteocalcin, serum P1NP and serum CTX-1 in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [47] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [48] 0 0
Change From Baseline in Bone Biomarkers-serum Bone-ALP, Osteocalcin, Serum P1NP and Serum Type 1 CTX-1 at Weeks 96 and 144
Assessment method [48] 0 0
Serum samples were collected for analysis of bone biomarkers. Baseline is latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen"
Timepoint [48] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [49] 0 0
Change From Baseline in Bone Biomarker: Serum 25-hydroxyvitamin D at Weeks 24 and 48
Assessment method [49] 0 0
Serum samples were collected for analysis of 25-hydroxyvitamin D. Baseline value was latest pre-dose assessment (Day 1) with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Adjusted mean and its corresponding standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for treatment, visit, Baseline third agent class, CD4+ cell count (continuous), age (continuous), sex, race, BMI (continuous), smoking status, vitamin D use, Baseline biomarker (continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor.One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [49] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [50] 0 0
Change From Baseline in Bone Biomarker: Serum 25-hydroxyvitamin D at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen
Assessment method [50] 0 0
Serum samples were collected for the analysis of 25-hydroxyvitamin D. Baseline value was the value from latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline values for serum 25-hydroxyvitamin D in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [50] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [51] 0 0
Change From Baseline in Bone Biomarker: Serum 25-hydroxyvitamin D at Weeks 96 and 144
Assessment method [51] 0 0
Serum samples were collected for analysis of 25-hydroxyvitamin D. Baseline value is latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen"
Timepoint [51] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [52] 0 0
Change From Baseline in Renal Biomarker- Serum Cystatin C at Weeks 24 and 48
Assessment method [52] 0 0
Serum samples were collected to assess renal biomarker. Baseline was latest pre-dose assessment value with non-missing value (Day 1). Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and its corresponding standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for following:treatment, visit, Baseline third agent class, CD4+ cell count(continuous), age(continuous), sex, race, BMI(continuous), presence of diabetes mellitus, presence of hypertension, Baseline biomarker(continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen"
Timepoint [52] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [53] 0 0
Change From Baseline in Renal Biomarker- Serum Cystatin C at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen
Assessment method [53] 0 0
Serum samples were collected at Baseline, Week 24 and Week 48 to assess renal inflammation biomarker - cystatin C. Baseline was defined as the latest pre-dose assessment value with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline values for serum cystatin -C biomarker in TDF based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [53] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [54] 0 0
Change From Baseline in Renal Biomarker- Serum Cystatin C at Weeks 96 and 144
Assessment method [54] 0 0
Serum samples were collected to assess renal biomarker. Baseline is latest pre-dose assessment value with non-missing value (Day 1). Change from Baseline is post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen"
Timepoint [54] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [55] 0 0
Change From Baseline in Renal Biomarker- Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24 and 48
Assessment method [55] 0 0
Serum samples assessed:serum GFR from cystatin C and from creatinine adjusted using CKD-EPI Baseline(Day 1) was value from latest pre-dose assessment with non-missing value. Change from Baseline is post-dose visit value minus Baseline value.Adjusted mean and standard error is presented.Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from repeated measures model adjusting for treatment, visit, Baseline third agent class,CD4+ cell count(continuous),age(continuous), sex, race, BMI(continuous),presence of diabetes mellitus, presence of hypertension, Baseline biomarker(continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen"
Timepoint [55] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [56] 0 0
Change From Baseline in Renal Biomarker- Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen
Assessment method [56] 0 0
Serum samples were collected at Baseline, Week 24 and Week 48 to assess renal inflammation biomarkers - serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI. Baseline was defined as the latest pre-dose assessment value with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline in serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [56] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [57] 0 0
Change From Baseline in Renal Biomarker- Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum GFR From Creatinine Adjusted Using CKD-EPI at Weeks 96 and 144
Assessment method [57] 0 0
Serum samples were collected to assess serum GFR from cystatin C and from creatinine adjusted for BSA. Baseline is defined as the latest pre-dose assessment value with a non-missing value (Day 1). Change from Baseline is post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen"
Timepoint [57] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [58] 0 0
Change From Baseline in Renal Biomarker- Serum Creatinine at Weeks 24 and 48
Assessment method [58] 0 0
Serum samples assessed: renal inflammation biomarker serum creatinine.Baseline(Day 1)was value from latest pre-dose assessment with non-missing value. Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and its corresponding standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from repeated measures model adjusting for treatment, visit, Baseline third agent class, CD4+ cell count(continuous), age(continuous), sex, race, BMI(continuous), presence of diabetes mellitus, presence of hypertension, Baseline biomarker(continuous), treatment by visit interaction, Baseline value by visit interaction, with visit as repeated factor. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen"
Timepoint [58] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [59] 0 0
Change From Baseline in Renal Biomarker- Serum Creatinine at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen
Assessment method [59] 0 0
Serum samples were collected at Baseline, Week 24 and Week 48 to assess renal inflammation biomarker - serum creatinine. Baseline was defined as the latest pre-dose assessment value with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline in serum creatinine in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
Timepoint [59] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [60] 0 0
Change From Baseline in Renal Biomarker- Serum Creatinine at Weeks 96 and 144
Assessment method [60] 0 0
Serum samples were collected to assess renal inflammation biomarker - serum creatinine. Baseline is defined as the latest pre-dose assessment value with a non-missing value (Day 1). Change from Baseline is post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen"
Timepoint [60] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [61] 0 0
Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Utility Score at Week 24 and 48
Assessment method [61] 0 0
EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. The health state is defined by combining the levels of answers from each of the 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health.
Timepoint [61] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [62] 0 0
Change From Baseline in EQ-5D-5L Utility Score at Weeks 96 and 144
Assessment method [62] 0 0
EQ-5D-5L questionnaire provides profile of participant function and global health state rating. Five-item measure has 1question assessing each of 5dimensions:mobility,self-care,usual activities,pain/discomfort,anxiety/depression and 5 levels for each dimension including 1=no problems,2=slight problems,3=moderate problems,4=severe problems,5=extreme problems. Health state is defined by combining levels of answers from each of 5 questions. Each health state is referred to in terms of a 5 digit code.Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state.EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health.Baseline is latest pre-dose assessment value with a non-missing value (Day 1).Change from Baseline is post-dose visit value minus Baseline value.
Timepoint [62] 0 0
Baseline (Day 1) and at Weeks 96 and 144
Secondary outcome [63] 0 0
Change From Baseline in EQ-5D-5L Thermometer Scores at Week 24 and 48
Assessment method [63] 0 0
EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset. Baseline was the latest pre-dose assessment value with a non-missing value (Day 1) and change from Baseline is defined as post-dose value minus Baseline value.
Timepoint [63] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [64] 0 0
Change From Baseline in EQ-5D-5L Thermometer Scores at Weeks 96 and 144
Assessment method [64] 0 0
EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Baseline is defined as the latest pre-dose assessment value with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value.
Timepoint [64] 0 0
Baseline (Day 1) and at Weeks 96 and 144

Eligibility
Key inclusion criteria
* Participant must be able to understand and comply with protocol requirements, instructions, and restrictions;
* Participant must be likely to complete the study as planned;
* Participant must be considered an appropriate candidate for participation in an investigative clinical trial with medication (example no active substance abuse, acute major organ disease, or planned long-term work assignments out of the country).
* Aged 18 years or older (or older where required by local regulatory agencies), at the time of signing the informed consent.
* HIV-1 infected men or women.
* 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.
* Must be on uninterrupted ART for at least 6 months prior to screening. Only the following regimens are allowed:

* Participant on a TAF-based regimen for at least 6 months as the initial regimen, or
* Participants who switched from a tenofovir disoproxil fumarate (TDF) first-regimen TAF, without any changes to the other drugs in their regimen, and have been on the TAF-based regimen for at least 3 months immediately prior to Screening i.e., the only switch made is from TDF to TAF. This switch must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must NOT have been done for suspected or established treatment failure. A switch from a PI boosted with ritonavir to the same PI boosted with cobicistat is allowed (and vice versa).
* 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 lactating, and at least one of the following conditions applies:

a. Non-reproductive potential defined as:
* Pre-menopausal females with one of the following:

* Documented tubal ligation
* Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion
* Hysterectomy
* Documented bilateral oophorectomy
* Post-menopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause [refer to laboratory reference ranges for confirmatory levels]). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

b. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and for at least 2 weeks after the last dose of study medication.
* The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception. All participants participating 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.
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and the protocol. Eligible participants or their legal guardians must sign a written informed consent form before any protocol-specified assessments are conducted.

Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Women who are 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/millimeter (mm)^3 are NOT exclusionary.
* Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
* Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* 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.
* Anticipated need for any hepatitis C virus (HCV) therapy during the first 48 weeks of the study, or anticipated need for HCV therapy based on interferon or for any drugs that have a potential for adverse drug-drug interactions with study treatment throughout the entire study period.
* 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.
* History or presence of allergy or intolerance to the study drugs or their components or drugs of their class.
* 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.
* Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
* Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any systemic immune suppressant.
* 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).
* Use of any regimen consisting of single or dual ART.
* Any evidence of major nucleoside reverse transcriptase inhibitor (NRTI) mutation or presence of any major INSTI resistance-associated mutation in any available prior resistance genotype assay test result, if known, must be provided to ViiV after screening and before randomization for review by ViiV Virology.
* Any verified Grade 4 laboratory abnormality.
* Alanine aminotransferase (ALT) >=5 times (*) the upper limit of normal (ULN) or ALT >=3 * ULN and bilirubin >=1.5 * ULN (with >35 percent [%] direct bilirubin).
* Creatinine clearance of <50 milliliter (mL)/minute/1.73 meter^2 via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method.
* Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL.
* Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, 2 or more plasma HIV-1 RNA measurements >=50 c/mL.
* Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current ART regimen, any plasma HIV-1 RNA measurement >=50 c/mL.
* 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.
* 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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/01/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/05/2022
Sample size
Target
Accrual to date
Final
743
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst, Sydney
Recruitment hospital [2] 0 0
GSK Investigational Site - Darlinghurst
Recruitment hospital [3] 0 0
GSK Investigational Site - Surry Hills
Recruitment hospital [4] 0 0
GSK Investigational Site - Sydney
Recruitment hospital [5] 0 0
GSK Investigational Site - Fortitude Valley
Recruitment hospital [6] 0 0
GSK Investigational Site - Carlton
Recruitment hospital [7] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [8] 0 0
GSK Investigational Site - North Fitzroy
Recruitment hospital [9] 0 0
GSK Investigational Site - Prahran
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst, Sydney
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2010 - Surry Hills
Recruitment postcode(s) [4] 0 0
2010 - Sydney
Recruitment postcode(s) [5] 0 0
4006 - Fortitude Valley
Recruitment postcode(s) [6] 0 0
3053 - Carlton
Recruitment postcode(s) [7] 0 0
3168 - Clayton
Recruitment postcode(s) [8] 0 0
3078 - North Fitzroy
Recruitment postcode(s) [9] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Nevada
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
Belgium
State/province [20] 0 0
Antwerpen
Country [21] 0 0
Belgium
State/province [21] 0 0
Brussels
Country [22] 0 0
Belgium
State/province [22] 0 0
Brussel
Country [23] 0 0
Belgium
State/province [23] 0 0
Gent
Country [24] 0 0
Canada
State/province [24] 0 0
Manitoba
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
Canada
State/province [26] 0 0
Quebec
Country [27] 0 0
France
State/province [27] 0 0
Bordeaux
Country [28] 0 0
France
State/province [28] 0 0
Marseille
Country [29] 0 0
France
State/province [29] 0 0
Nice
Country [30] 0 0
France
State/province [30] 0 0
Paris Cedex 13
Country [31] 0 0
France
State/province [31] 0 0
Paris
Country [32] 0 0
France
State/province [32] 0 0
Tourcoing cedex
Country [33] 0 0
Germany
State/province [33] 0 0
Bayern
Country [34] 0 0
Germany
State/province [34] 0 0
Hessen
Country [35] 0 0
Germany
State/province [35] 0 0
Niedersachsen
Country [36] 0 0
Germany
State/province [36] 0 0
Nordrhein-Westfalen
Country [37] 0 0
Germany
State/province [37] 0 0
Berlin
Country [38] 0 0
Germany
State/province [38] 0 0
Hamburg
Country [39] 0 0
Germany
State/province [39] 0 0
München
Country [40] 0 0
Japan
State/province [40] 0 0
Aichi
Country [41] 0 0
Japan
State/province [41] 0 0
Chiba
Country [42] 0 0
Japan
State/province [42] 0 0
Tokyo
Country [43] 0 0
Netherlands
State/province [43] 0 0
Rotterdam
Country [44] 0 0
Spain
State/province [44] 0 0
Galicia
Country [45] 0 0
Spain
State/province [45] 0 0
Alcala de Henares
Country [46] 0 0
Spain
State/province [46] 0 0
Alicante
Country [47] 0 0
Spain
State/province [47] 0 0
Badalona
Country [48] 0 0
Spain
State/province [48] 0 0
Barcelona
Country [49] 0 0
Spain
State/province [49] 0 0
Cartagena (Murcia)
Country [50] 0 0
Spain
State/province [50] 0 0
Elche
Country [51] 0 0
Spain
State/province [51] 0 0
Granada
Country [52] 0 0
Spain
State/province [52] 0 0
Granollers (Barcelona)
Country [53] 0 0
Spain
State/province [53] 0 0
Huelva
Country [54] 0 0
Spain
State/province [54] 0 0
L'Hospitalet de Llobregat
Country [55] 0 0
Spain
State/province [55] 0 0
Madrid
Country [56] 0 0
Spain
State/province [56] 0 0
Majadahonda (Madrid)
Country [57] 0 0
Spain
State/province [57] 0 0
Marbella
Country [58] 0 0
Spain
State/province [58] 0 0
Mataró
Country [59] 0 0
Spain
State/province [59] 0 0
Murcia
Country [60] 0 0
Spain
State/province [60] 0 0
Málaga
Country [61] 0 0
Spain
State/province [61] 0 0
Santiago de Compostela
Country [62] 0 0
Spain
State/province [62] 0 0
Sevilla
Country [63] 0 0
Spain
State/province [63] 0 0
Valencia
Country [64] 0 0
Spain
State/province [64] 0 0
Vilajoyosa
Country [65] 0 0
Spain
State/province [65] 0 0
Zaragoza
Country [66] 0 0
United Kingdom
State/province [66] 0 0
West Midlands
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Birmingham
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Brighton
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Bristol
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Crumpsall, Manchester
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Liverpool
Country [72] 0 0
United Kingdom
State/province [72] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ViiV Healthcare
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
GlaxoSmithKline
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
ViiV Healthcare
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03446573