A Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Fixed Dose Combination (FDC) Versus a Regimen Consisting of Darunavir/Cobicistat FDC With Emtricitabine/Tenofovir Disoproxil Fumarate FDC in Treatment-naive HIV Type 1 Infected Subjects

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate non-inferiority in efficacy of a darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed dose combination (FDC) tablet versus Darunavir/Cobicistat (DRV/COBI) FDC coadministered with Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) FDC in human immunodeficiency virus-1 (HIV-1) infected, antiretroviral (ARV) treatment naive adult participants.

Detailed Description
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This is a Phase 3, multicenter (when more than one hospital or medical school team work on a medical research study), randomized (study drug assigned by chance), double-blind (a medical research study in which neither the researchers nor the participant know what treatment the participant is receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard [control] treatment or procedure) study. The study consists of 5 periods: a Screening period, Double-blind treatment period, Single-arm treatment period, Extension period and a Follow-up period. Participants will receive either darunavir (DRV)/ cobicistat (COBI)/emtricitabine (FTC) /tenofovir alafenamide (TAF) fixed dose combination (D/C/F/TAF FDC) or DRV/COBI FDC along with FTC/TDF FDC. Primarily percentage of participants with human immunodeficiency virus (HIV) -1 Ribonucleic acid (RNA) less than (<) 50 copies per milliliter (copies/ml) defined by snapshot analysis will be evaluated. Participants' safety will be monitored throughout the study.

Official Title
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A Phase 3, Randomized, Active-controlled, Double-blind Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Once Daily Fixed Dose Combination Regimen Versus a Regimen Consisting of Darunavir/Cobicistat Fixed Dose Combination Coadministered With Emtricitabine/Tenofovir Disoproxil Fumarate Fixed Dose Combination in Antiretroviral Treatment-naive Human Immunodeficiency Virus Type 1 Infected Subjects

Conditions
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Immunodeficiency Virus Type 1, Human

Intervention / Treatment
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* Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC
* Drug: DRV/COBI FDC
* Drug: FTC/TDF FDC
* Drug: D/C/F/TAF FDC - Matching Placebo
* Drug: FTC/TDF FDC Matching Placebo
* Drug: DRV/COBI FDC Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be antiretroviral (ARV) treatment-naive (never treated with an ARV including post-exposure prophylaxis and pre-exposure prophylaxis); no prior use of any approved or experimental anti- human immunodeficiency virus (anti-HIV) drug for any length of time Screening plasma HIV-1 ribonucleic acid (RNA) level greater than or equal to >=1,000 copies per milliliter (copies/mL) Cluster of Differentiation 4+ (CD4+) cell count >50 cells/microliter (cells/mcL) Screening HIV-1 genotype report must show full sensitivity to DRV, TDF and FTC Screening eGFRcreatinine >=70 mL/min according to the Cockcroft-Gault formula for creatinine clearance Exclusion Criteria: Subject has been diagnosed with a new acquired immunodeficiency syndrome (AIDS)-defining condition within the 30 days prior to screening Subject has proven or suspected acute hepatitis within 30 days prior to screening Subject is hepatitis C or hepatitis B positive Subject has a history of cirrhosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide<br>Subject will receive a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching and FTC/TDF FDC-matching placebo tablets once daily up to Week 48 analysis unblinding visit (i.e. after last subject has reached Week 48). After Week 48 analysis unblinding visit, subjects will receive a single tablet containing D/C/F/TAF FDC once daily up to Week 96. | Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC<br>* A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF) 10 mg will be administered once daily.<br>Drug: FTC/TDF FDC Matching Placebo<br>* Matching placebo of FTC/TDF FDC will be administered once daily.<br>Drug: DRV/COBI FDC Matching Placebo<br>* Matching placebo of DRV/COBI FDC will be administered once daily.<br>|
| Active Comparator: DRV/COBI fixed dose combination (FDC) and FTC/TDF FDC<br>Subject will receive DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48 analysis unblinding (i.e. after last subject has reached Week 48). After Week 48 analysis unblinding, subjects will receive a single tablet containing D/C/F/TAF FDC once daily up to Week 96. | Drug: DRV/COBI FDC<br>* A tablet containing DRV 800 mg and COBI 150 mg will be administered once daily.<br>Drug: FTC/TDF FDC<br>* A tablet containing FTC 200 mg and TDF 300 mg will be administered once daily.<br>Drug: D/C/F/TAF FDC - Matching Placebo<br>* Matching placebo of D/C/F/TAF FDC will be administered once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies Per mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach | Percentage of participants with a HIV-1 RNA < 50 copies per mL were assessed using FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA < 20/50/200 copies per mL at Week 48), 2) virologic failure (HIV RNA greater than or equal to [>=] 20/50/200 copies per mL at Week 48), 3) no viral load data in the Week 48 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response. | At Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach | Percentage of participants with HIV-1 RNA < 20/200 copies per mL using FDA snapshot approach were reported. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA < 20/50/200 copies per mL at Week 48 and 96), 2) virologic failure (HIV RNA >= 20/50/200 copies per mL at Week 48 and 96), 3) no viral load data in the Week 48 and 96 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response. | At Weeks 48 and 96 | 
| Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | Percentage of participants with HIV-1 RNA less than (<) 20, 50, and 200 copies per mL at Weeks 48 and 96 based on TLOVR algorithm were assessed. TLOVR requires sustained HIV-1 RNA < 50 copies per mL; confirmed HIV-1 RNA >= 50 copies per mL is considered as non-response (rebound); participant is considered non-responder after permanent discontinuation. | At Week 48 and 96 | 
| Change From Baseline in log10 HIV-1 RNA Levels at Week 48 | Change from baseline in log10 HIV-1 RNA levels were reported. | Baseline and Week 48 | 
| Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Week 48 | The immunologic change was determined by changes in Cluster of CD4+ cell count. Change from baseline in CD4+ cell count at Week 48 were assessed. | Baseline and Week 48 | 
| Change From Baseline in Serum Creatinine at Week 48 | Change from baseline in serum creatinine at Week 48 was reported. | Baseline and Week 48 | 
| Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Formula at Week 48 | Change from baseline in eGFRcr was calculated using the CKD-EPI equation as per which Stage 1 (normal or high GFR [>=90 mL/min]); Stage 2 (Mild CKD [60 to 90 mL/min]); Stage 3 (Moderate CKD [30 to 59mL/min]); Stage 4 (Severe CKD [15 to 29 mL/min]); Stage 5 (End Stage CKD [<15 mL/min]). The eGFRcr was assessed by calculating serum creatinine (Scr) using the equation: eGFRcr milliliter per minute per 1.72 meter square (mL/min/1.73m^2) = 144*(Scr/0.7)^-0.329*0.993^age (Scr =< 0.7 mg/dL) and eGFRcr mL/min/1.73m^2 = 144*(Scr/0.7)^-1.209*0.993^age (Scr >0.7 mg/dL) for female participants and eGFRcr mL/min/1.73m^2 = 141*(Scr/0.9)^-0.411*0.993^age (Scr =<0.9 mg/dL) and eGFRcr mL/min/1.73m^2 = 141*(Scr/0.9)^-1.209*0.993^age (Scr >0.9 mg/dL) for male participants. | Baseline and Week 48 | 
| Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine by (Cockcroft-Gault Formula) at Week 48 | Change from baseline in eGFRcr by cockcroft-gault formula at Week 48. The eGFRcr was assessed by calculated creatinine clearance (CrCl) using the Cockcroft-Gault formula, and was assessed using CrCl [mL/min] = (140 - A) * W / (72 * C) * R. Where A is age at sample date [years], W is body weight at specific visit (kilogram [kg]), C is the serum concentration of creatinine [mg/dL], R = 1 if the participant is male and = 0.85 if female. | Baseline and Week 48 | 
| Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula at Week 48 | Change from baseline in eGFRcyst was calculated using the CKD-EPI equation as per which Stage 1 (normal or high GFR) >= 90 indicates normal kidney function; Stage 2 (Mild CKD): 60 to 89 mL/min indicates mildly reduced kidney function; Stage 3 (Moderate CKD): 30 to 59 mL/min indicates moderately reduced kidney function; Stage 4 (Severe CKD): 15 to 29 mL/min indicates severely reduced kidney function; Stage 5 (End Stage of CKD): <15 mL/min indicate very severe or end stage kidney failure. The eGFRcyst was assessed by calculated serum cystatin C (Scyst) using the equation: eGFRcyst mL/min/1.73m^2 = 133 * (Scyst/0,8)^-0.499 * 0.996^age [* 0.932 if female] (Scyst =<0.8 mg/L) and eGFRcr mL/min/1.73m^2 = 133 * (Scyst/0,8)^-1.328 * 0.996^age [* 0.932 if male] (Scyst >0.8 mg/L). | Baseline and Week 48 | 
| Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48 | AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (AE) that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. | Up to Weeks 48 | 
| Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Week 48 | Change from baseline in UPCR at Week 48 was reported. | Baseline and Week 48 | 
| Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) at Week 48 | Change from baseline in UACR at Week 48 was reported. | Baseline and Week 48 | 
| Change From Baseline in Urine Retinol Binding Protein To Creatinine Ratio (URBPCR) at Week 48 | Change from baseline in URBPCR at Week 48 were reported. | Baseline and Week 48 | 
| Change From Baseline in Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Week 48 | Change from baseline in UB2MGCR at Week 48 were reported. | Baseline and Week 48 | 
| Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Week 48 | Percent change from baseline in FEPO4 at Week 48 was reported. | Baseline and Week 48 | 
| Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC0-24h) of Darunavir | AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours post-dose. | 0 to 24 hours post dose | 
| Predose (Trough) Plasma Concentration (C0h) of Darunavir | C0h is defined as the predose (trough) plasma concentration or concentration just prior to study drug administration. | 30 minutes to 4 hours postdose at Weeks 2, 4, 12, 24 and 48 and at 2 timepoints with at least 2.5 hours in between sampling at Week 8 and 36 (first sample between 1 and 4 hours postdose) | 
| Area Under the Plasma Concentration Time Curve Across the Dosing Interval (AUCtau) of Tenofovir Alafenamide | The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption. | 30 minutes to 4 hours postdose at Weeks 2, 4, 12, 24 and 48 and at 2 timepoints with at least 2.5 hours in between sampling at Week 8 and 36 (first sample between 1 and 4 hours postdose) | 
| Plasma Concentrations 2 Hours After Dosing (C0-2h) of Tenofovir Alafenamide | C0-2h is defined as the plasma concentrations 2 hours after dosing. | 0 to 2 hours post dose | 
| Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD) | The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by dual energy x-ray absorptiometry (DEXA) scan. Positive values are best values and negative values are worst values of change. Percent change from baseline in hip and spine BMD was assessed. | Baseline, Weeks 24 and 48 | 
| Change From Baseline in BMD T-score of Hip and Spine | BMD status was assessed using BMD T-scores; normal bone status was defined by a BMD T-score >= -1, osteopenia by a T-score >= -2.5 to <-1.0, and osteoporosis by a T-score <-2.5. | Baseline, Weeks 24 and 48 | 
| Change From Baseline in Alkaline Phosphatase (ALP) Levels at Weeks 24 and 48 | Change from baseline in ALP at Weeks 24 and 48 was reported. | Baseline, Weeks 24 and 48 | 
| Change From Baseline in Levels of Serum Procollagen 1 N-Terminal Propeptide (P1NP) at Weeks 24 and 48 | Change from baseline in serum P1NP at Weeks 24 and 48 were reported. | Baseline, Weeks 24 and 48 | 
| Change From Baseline in Levels of Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) at Weeks 24 and 48 | Change from baseline in serum CTX at Weeks 24 and 48 were reported. | Baseline, Weeks 24 and 48 | 
| Change From Baseline in Levels of Parathyroid Hormone (PTH) at Weeks 24 and 48 | Change from baseline in PTH at Weeks 24 and 48 were reported. | Baseline, Weeks 24 and 48 | 
| Change From Baseline in Levels of 25-Hydroxyvitamin D (25-OH Vitamin D), at Week 24 and 48 | Change from baseline in 25-OH Vitamin D levels at Week 24 and 48 were reported. | Baseline, Weeks 24 and 48 | 
| Percentage of Participants With HIV-1 RNA <50 Copies Per mL at Week 96 Defined by FDA Snapshot Approach | Percentage of participants with a HIV-1 RNA < 50 copies per mL were assessed using FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA < 20/50/200 copies per mL at Week 96), 2) virologic failure (HIV RNA greater than or equal to [>=] 20/50/200 copies per mL at Week 96), 3) no viral load data in the Week 96 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response. | At Week 96 | 
| Change From Reference in log10 HIV-1 RNA Levels at Week 96 | Change from reference in log10 HIV-1 RNA levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for Test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in CD4+ Cell Count at Week 96 | The immunologic change was determined by changes in cluster of differentiation (CD4+) cell count. Change from reference in CD4+ cell count at Week 96 was assessed. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Percentage of Participants With >95% Treatment Adherence Assessed by Drug Accountability | Treatment adherence assessed by drug accountability (based on pill count) from start of treatment/switch to last study drug intake by determination of the cumulative treatment adherence in participants who returned all dispensed bottles prior to or at the last visit in the study. Adherent participants were defined as having an adherence >95% as assessed by drug accountability. | Baseline to Switch and switch to EOE to Open-Label D/C/F/TAF (Up to 3 years) | 
| Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96 | AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (AE) that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. | Up to Week 96 | 
| Change From Reference in Serum Creatinine | Change from reference in serum creatinine was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in eGFRcr by CKD-EPI Formula | Change from reference in eGFRcr was calculated using the CKD-EPI equation as per Stage 1 (normal or high GFR) to Stage 5 (End Stage of CKD). The eGFRcr was assessed by calculating serum creatinine (Scr) using the CKD-EPI equation: eGFRcr milliliter per minute per 1.72 meter square (mL/min/1.73m^2) = 144 * (Scr/0.7)^-0.329 * 0.993^age (Scr =< 0.7 mg/dL) and eGFRcr mL/min/1.73m^2 = 144 * (Scr/0.7)^-1.209 * 0.993^age (Scr >0.7 mg/dL) for female participants and eGFRcr mL/min/1.73m^2 = 141 x (Scr/0.9)^-0.411 x 0.993^age (Scr =<0.9 mg/dL) and eGFRcr mL/min/1.73m^2 = 141 * (Scr/0.9)^-1.209 x 0.993^age (Scr >0.9 mg/dL) for male participants. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine by Cockcroft-Gault Formula | Change from reference in eGFRcr by cockcroft-gault formula was reported. The eGFRcr was assessed by calculated creatinine clearance (CrCl) using the Cockcroft-Gault formula, and was assessed using CrCl [mL/min] = (140 - A) * W / (72 * C) * R. Where A is age at sample date [years], W is body weight at specific visit (kilogram [kg]), C is the serum concentration of creatinine [mg/dL], R = 1 if the participant is male and = 0.85 if female. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula | Change from reference in eGFRcyst was calculated using the CKD-EPI equation as per Stage 1 (normal or high GFR) to Stage 5 (End Stage of CKD): <15 mL/min indicate very severe or end stage kidney failure. The eGFRcyst was assessed by calculated serum cystatin C (Scyst) using the CKD-EPI equation: eGFRcyst mL/min/1.73m^2 = 133 * (Scyst/0,8)^-0.499 * 0.996^age [x 0.932 if female] (Scyst =<0.8 mg/L) and eGFRcr mL/min/1.73m^2 = 133 * (Scyst/0,8)^-1.328 * 0.996^age [* 0.932 if male] (Scyst >0.8 mg/L). Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in UPCR | Change from reference in UPCR was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in UACR | Change from reference in UACR at Week 96 was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in URBPCR | Change from reference in URBPCR at Week 96 were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in UB2MGCR | Change from reference in UB2MGCR was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Percent Change From Reference in Urine FEPO4 | Percent change from reference in FEPO4 at Week 96 were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Percent Change From Reference in Hip and Spine BMD | The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by DEXA scan. Positive values are best values and negative values are worst values of change. Percent change from reference in hip and spine BMD was assessed. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in BMD T-score of Hip and Spine at Week 96 | BMD status was assessed using BMD T-scores; normal bone status was defined by a BMD T-score >= -1, osteopenia by a T-score >= -2.5 to <-1.0, and osteoporosis by a T-score <-2.5. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in ALP Levels | Change from reference in ALP levels at Week 96 was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in Levels of Serum P1NP | Change from reference in serum P1NP levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in Levels of Serum CTX | Change from reference in serum CTX levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in Levels of PTH | Change from reference in PTH levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Change From Reference in Levels of 25-OH Vitamin D | Change from reference in 25-OH Vitamin D were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | 
| Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Percentage of participants with HIV RNA <50, <20, and <200 copies/mL post Week 96 to end of extension were reported. | Week 96 to end of extension (up to 3 years) | 
| Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Percentage of participants with PDVF were reported. Protocol-defined virologic failure was defined as having virologic non-response (HIV-1 RNA <1 log10 reduction from baseline and >=50 copies/mL at the Week 8 visit, confirmed at the next visit), virologic rebound (confirmed HIV-1 RNA >=50 copies/mL after confirmed consecutive HIV-1 RNA <50 copies/mL or confirmed >1 log10 increase in HIV-1 RNA from nadir), or viremic at final time point (final available on treatment HIV-1 RNA >=400 copies/mL). | From Baseline up to Week 96 | 
| Percentage of Participants With PDVF Post-week 96 to End of Extension | Percentage of participants with PDVF were reported. Protocol-defined virologic failure was defined as having virologic non-response (HIV-1 RNA <1 log10 reduction from baseline and >=50 copies/mL at the Week 8 visit, confirmed at the next visit), virologic rebound (confirmed HIV-1 RNA >=50 copies/mL after confirmed consecutive HIV-1 RNA <50 copies/mL or confirmed >1 log10 increase in HIV-1 RNA from nadir), or viremic at final time point (final available on treatment HIV-1 RNA >=400 copies/mL). | Week 96 to end of extension (up to 3 years) | 
| Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Percentage of participants with non-PDVF by Kaplan-Meier Estimates were reported. PDVF was defined as having virologic non-response (HIV-1 RNA <1 log10 reduction from baseline and >=50 copies/mL at the Week 8 visit, confirmed at the next visit), virologic rebound (confirmed HIV-1 RNA >=50 copies/mL after confirmed consecutive HIV-1 RNA <50 copies/mL or confirmed >1 log10 increase in HIV-1 RNA from nadir), or viremic at final time point (final available on treatment HIV-1 RNA >=400 copies/mL). | From Week 96 to end of extension (up to 2 years and 6 months) | 
| Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Percentage of participants with time to treatment failure by Kaplan-Meier Estimates were reported. Treatment failure was defined as having either protocol-defined virologic failure or having discontinued for reasons other than alternate access to D/C/F/TAF (or other ARVs). | From Week 96 to end of extension (up to 3 years) | 
| CD4+ Cell Count Post-Week From 96 to End of Extension | The immunologic change was determined by Cluster of CD4+ cell count. CD4+ cell count post-Week 96 to end of extension were assessed. | Week 96 to end of extension (up to 3 years) | 
| Number of Participants With ARV Resistance | Number of participants with DRV, FTC, TDF/TAF resistance were reported. | Baseline to end of extension (up to 4 years) | 
| Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension | AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (AE) that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. | From Week 96 to end of extension (up to 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunodeficiency Virus Type 1, Human, Darunavir, Cobicistat, Tenofovir Alafenamide, Emtricitabine, Tenofovir Disoproxil Fumarate