Human Immunodeficiency Virus Type 1
Conditions
Keywords
Human Immunodeficiency Virus Type 1, Emerald, Darunavir, Cobicistat, Emtricitabine, Tenofovir Alafenamide
Brief summary
The purpose of this study is to demonstrate non-inferiority in efficacy while switching to a once-daily single-tablet regimen containing darunavir (DRV)/ cobicistat (COBI)/ emtricitabine (FTC)/ tenofovir alafenamide (TAF) (D/C/F/TAF tablet) relative to continuing the current regimen consisting of a boosted protease inhibitor (bPI) combined with tenofovir disoproxil fumarate (FTC/TDF) in virologically-suppressed (human immunodeficiency virus type 1 ribonucleic acid \[HIV-1 RNA\] concentrations less than \[\<\] 50 copies per milliliter \[copies/mL\]) HIV-1 infected participants.
Detailed description
This is a randomized (study medication assigned to participants by chance), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), open-label (participants and researchers are aware about the treatment, participants are receiving), multicenter (when more than 1 hospital or medical school team work on a medical research study), study in virologically-suppressed, HIV-1 infected adult participants. The study will include a Screening Period of approximately 30 days (up to maximum 6 weeks), a controlled Treatment Period of 48 weeks, an Extension Phase of 48 weeks. All eligible participants will be randomly assigned to receive either current treatment regimen - a bPI (limited to DRV with low-dose ritonavir \[rtv\] or COBI, atazanavir \[ATV\] with rtv or COBI, or lopinavir \[LPV\] with rtv) combined with FTC/TDF, or experimental treatment regimen - D/C/F/TAF once-daily single-tablet for 48 weeks. After completion of week 48, participants assigned to the experimental treatment will continue with D/C/F/TAF in the extension phase up to week 96 . Participants who continued their current regimen will receive the experimental treatment (if all criteria are fulfilled) at week 52 up to week 96. As from Week 96, all participants will be given the option to continue D/C/F/TAF treatment, if they wish and if they continue to benefit from it until D/C/F/TAF becomes commercially available and is reimbursed, or can be accessed through another source in the country where he/she is living,or until the sponsor terminates clinical development. A bone investigation substudy will be performed at selected study sites, to assess bone biomarkers and energy x-ray absorptiometry (DXA) scans, in approximately 300 participants (200 in the D/C/F/TAF treatment arm versus 100 in the control arm) who provide informed consent for the substudy.
Interventions
DRUGD/C/F/TAF
Once-daily single-tablet regimen containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg.
DRUGBoosted Protease Inhibitor (bPI)
Boosted protease inhibitor (limited to darunavir \[DRV\] or atazanavir with low-dose ritonavir \[rtv\] or cobicistat \[COBI\], or lopinavir with rtv) as per current treatment regimen.
DRUGFTC/TDF
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF).
Sponsors
Janssen R&D Ireland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Currently being treated with a stable antiretroviral (ARV) regimen consisting of a boosted protease inhibitor (limited to darunavir \[DRV\] or atazanavir with low-dose ritonavir \[rtv\] or cobicistat \[COBI\], or lopinavir with rtv) combined with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) only, for at least 6 consecutive months preceding the Screening visit * On-treatment plasma human immunodeficiency virus type 1 ribonucleic acid (HIV-1 RNA) concentrations less than (\<) 50 copies per milliliter (copies/mL) or HIV-1 RNA undetectable by a local HIV-1 RNA test between 12 and 2 months prior to the Screening visit and have HIV-1 RNA \<50 copies/mL at the Screening visit * A single virologic elevation of greater than or equal to (\>=) 50 copies/mL after previously reaching viral suppression between 12 and 2 months prior to Screening is acceptable, provided a subsequent test prior to Screening was \<50 copies/mL * Absence of history of failure on DRV treatment and absence of DRV resistance-associated mutations (RAMs), if documented historical genotypes are available * Normal electrocardiogram (ECG) at Screening (or if abnormal, determined by the Investigator to be not clinically significant)
Exclusion criteria
* A new acquired immunodeficiency syndrome (AIDS) - defining condition diagnosed within the 30 days prior to Screening * Proven or suspected acute hepatitis within 30 days prior to study entry * Hepatitis C antibody positive; however, participants previously cured of hepatitis C virus (HCV) infection, with documented sustained virologic response, that is, undetectable HCV RNA 24 weeks after the last dose of HCV treatment, are allowed to participate * Hepatitis B surface antigen (HBsAg) positive * Participants with cirrhosis as diagnosed based on local practices
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 48 | Through Week 48 | Virologic rebound was defined as: confirmed plasma human immunodeficiency virus - 1 (HIV-1) Ribonucleic Acid (RNA) level greater than or equal to (\>=)50 copies per milliliter (copies/mL) up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA \>=50 copies/mL at premature discontinuation (irrespective of reason). Percentage of participants with virologic rebound were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=200 Copies/mL) Cumulative Through 48 Weeks | Through 48 Weeks | Virologic rebound was defined as: confirmed plasma HIV-1 RNA \>=200 copies/mL up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA \>=200 copies/mL at premature discontinuation (irrespective of reason). Percentage of participants with virologic rebound were reported. |
| Percentage of Participants With Non-Virologic Rebound at Week 48 by Kaplan-Meier Estimates | Baseline up to Week 48 | Virologic rebound was defined as: confirmed plasma HIV-1 RNA \>=50 copies/mL up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA \>=50 copies/mL at premature discontinuation (irrespective of reason). Here Kaplan-Meier estimates percentage of participants with non-virologic rebound at week 48. |
| Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48 | Up to Week 48 | An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events were symptoms causing inability to perform usual social & functional activities. Grade 4 (Life-threatening) events were symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. |
| Change From Baseline in Serum Creatinine Levels at Weeks 24 and 48 | Baseline and Weeks 24 and 48 | Change from baseline in serum creatinine levels at Weeks 24 and 48 was assessed. |
| Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Change from baseline in eGFRcr (by Cockcroft-Gault formula) was assessed at Weeks 24 and 48. eGFRcr according to the Cockcroft Gault formula- Male: (140 - age in years)\*(weight in kilogram \[kg\])/72\*(serum creatinine in milligram per deciliter \[mg/dL\])=eGFRcr (milliliter per minute \[mL/min\]); Female: (140 - age in years)\*(weight in kg)/72\*(serum creatinine in mg/dL)\*0.85=eGFRcr (mL/min). |
| Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Change from baseline in eGFRcr (by CKD-EPI) was assessed at Weeks 24 and 48. eGFRcr per CKD-EPI formula - Female: 1) Serum creatinine (Scr) less than or equal to (\<=)0.7 mg/dL: 144\*(Scr/0.7)\^-0.329\*0.993age; 2) Scr greater than (\>)0.7 mg/dL: 144\*(Scr/0.7)\^-1.209\*0.993age. Male: 1) Scr \<=0.9 mg/dL: 141\*(Scr/0.9)\^-0.411\*0.993age; 2) Scr \>0.9 mg/dL: 141\*(Scr/0.9)\^-1.209\*0.993age. |
| Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Change from baseline in eGFRcyst (by CKD-EPI) was assessed at Weeks 24 and 48. eGFRcyst according to the CKD-EPI formula - 1) Serum Cystatin C (Scyst) \<=0.8 mg/L: 133\*(Scyst/0.8)\^-0.499\*0.996age (\*0.932 if female); 2) Scyst \>0.8 mg/L: 133\*(Scyst/0.8)\^-1.328\*0.996age (\*0.932 if female). |
| Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Change from baseline in UACR and UPCR was assessed at Weeks 24 and 48. Lower levels of albumin or protein in the urine indicates better proximal tubular function. |
| Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Change from baseline in URBPCR and UB2MGCR was assessed at Weeks 24 and 48. Retinol binding protein is a marker of proximal tubular function. |
| Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Percent change from baseline in urine FEPO4 was assessed at Weeks 24 and 48. |
| Percentage of Participants With Virologic Response Based on HIV-1 RNA Less Than (<)20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Food and Drug Administration (FDA) Snapshot Approach | Week 48 | Percentage of participants with virologic response based on HIV-1 RNA \<20, \<50, and \<200 copies/mL threshold were analyzed at Week 48 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic response was defined as HIV-1 RNA \<20/50/200 copies/mL (observed case). |
| Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | Week 48 | Percentage of participants with virologic response based on HIV-1 RNA \<20, \<50, and \<200 copies/mL threshold were analyzed at Week 48 using TLOVR algorithm approach. TLOVR was defined as sustained HIV-1 RNA \<20/50/200 copies/mL. |
| Change From Baseline in Cluster of Differentiation 4 Plus (CD4+) Cell Count at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Change from baseline in CD4+ cell count was assessed at Weeks 24 and 48. |
| Percentage of Participants With Treatment Adherence of Greater Than (>)95 Percent (%) (Approach 1) Through Week 48 | Through Week 48 | Treatment adherence (defined as adherence of \>95%) was assessed by the drug accountability cumulative through Week 48 (Approach 1). |
| Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 48 | Through Week 48 | Treatment adherence (defined as adherence of \>95%) was assessed by the drug accountability cumulative treatment adherence up to time point where not more than one bottle was missing, or if available, through Week 48, whichever came sooner (Approach 2). |
| Number of Participants With Resistance to Study Drug | Up to Week 48 | HIV-1 genotypes were analyzed from samples of participants with confirmed virologic rebound (virologic rebound was defined as: confirmed HIV-1 RNA \>=50 copies/mL up to, and including the upper bound of the Week 48 window) and with HIV-1 RNA value \>=400 copies/mL or who discontinued with last HIV-1 RNA \>=400 copies/mL. Number of participants who developed resistance to any of the study drug was determined. |
| Predose (Trough) Plasma Concentration (C0h) of Darunavir | Predose at Weeks 2, 4, 8, 12, 24, 36, and 48 | Predose (trough) plasma concentration (C0h) of darunavir was determined. Pharmacokinetic (PK) data was only analyzed for participants in the D/C/F/TAF group as per planned analysis. |
| Percent Change From Baseline in Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) Levels at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Percent change from baseline in bone biomarkers: P1NP and CTX was assessed at Weeks 24 and 48. |
| Percent Change From Baseline in Parathyroid Hormone (PTH) at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Percent change from baseline in bone biomarker: PTH was assessed at Weeks 24 and 48. |
| Percent Change From Baseline in 25-hydroxy Vitamin D at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Percent change from baseline in bone biomarker: 25-hydroxy vitamin D was assessed at Weeks 24 and 48. |
| Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Percent change from baseline in spine and hip BMD was assessed at Weeks 24 and 48. |
| Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Change from baseline in spine, hip, and femoral neck BMD T-Score was assessed at Week 24 and 48. T-score values \>= -1.0 were considered normal, T-score values \< -1.0 to -2.5 indicate osteopenia and T-score values \< -2.5 indicate osteoporosis. |
| Percentage of Participants With Virologic Rebound (HIV-1 RNA >=20 Copies/mL) Cumulative Through Week 96 | Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm) | Virologic rebound was defined as: confirmed plasma HIV-1 RNA level \>=20 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA \>=20 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA \>=20 copies/mL at the study cutoff of Week 96 (that is, any last viral load \[re\]test having occurred no later than 6 weeks after Week 96). Percentage of participants with virologic rebound were reported. |
| Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 96 | Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm) | Virologic rebound was defined as: confirmed plasma HIV-1 RNA level \>=50 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA \>=50 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA \>=50copies/mL at the study cutoff of Week 96 (that is, any last viral load \[re\]test having occurred no later than 6 weeks after Week 96). Percentage of participants with virologic rebound were reported. |
| Percentage of Participants With Virologic Rebound (HIV-1 RNA >=200 Copies/mL) Cumulative Through Week 96 | Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm) | Virologic rebound was defined as: confirmed plasma HIV-1 RNA level \>=200 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA \>=200 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA \>=200 copies/mL at the study cutoff of Week 96 (that is, any last viral load \[re\]test having occurred no later than 6 weeks after Week 96). Percentage of participants with virologic rebound were reported. |
| Percentage of Participants With Non-Virologic Rebound at Week 96 by Kaplan-Meier Estimates | Baseline to Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm) | Here Kaplan-Meier estimates percentage of participants with non-virologic rebound at Week 96. |
| Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | Week 96 (Comprising up to Week 96 for D/C/F/TAF and 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52 up to Week 96]) | Percentage of participants with virologic response based on HIV-1 RNA \<20, \<50, and \<200 copies/mL threshold were analyzed at Week 96 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic response was defined as having last available HIV-1 RNA \<20/50/200 copies/mL (observed case). |
| Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the TLOVR Algorithm | Week 96 (Comprising up to Week 96 for D/C/F/TAF and 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52 up to Week 96]) | Percentage of participants with virologic response based on HIV-1 RNA \<20, \<50, and \<200 copies/mL threshold were analyzed at Week 96 using TLOVR algorithm approach. TLOVR was defined as sustained HIV-1 RNA \<20/50/200 copies/mL. |
| Percentage of Participants With Virologic Failure Based on HIV-1 RNA >=20, >=50, and >=200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | Week 96 (Comprising up to Week 96 for D/C/F/TAF and 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52 up to Week 96]) | Percentage of participants with virologic failure based on HIV-1 RNA \>=20, \>=50, and \>=200 copies/mL threshold were analyzed at Week 96 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic failure was defined by the FDA snapshot approach as having last available HIV-1 RNA \>=20/50/200 copies/mL at Week 96; virologic failure - leading to discontinuation; virologic failure - discontinued due to other reason and last available HIV-1 RNA \>=20/50/200 copies/mL. |
| Change From Reference in CD4+ Cell Count at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF (Comprising 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52]) | Change from reference in CD4+ cell count was assessed at Week 96. The change from reference in CD4+ count at a given time point is defined as: CD4+ at a given time point minus reference CD4+. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Number of Participants With Resistance to Study Drug Through Week 96 | Through Week 96 (D/C/F/TAF arm), up to Week 48 (Control arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm) | HIV-1 genotypes were analyzed from samples of participants with confirmed virologic rebound in case they had HIV-1 RNA values \>=400 copies/mL at failure or at later time points, including participants who discontinued with last HIV-1 RNA \>=400 copies/mL. Virologic rebound was defined as: confirmed plasma HIV-1 RNA level \>=20 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA \>=20 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA \>=20 copies/mL at the study cutoff of Week 96 (that is, any last viral load \[re\]test having occurred no later than 6 weeks after Week 96). Number of participants who developed resistance to any of the study drug (DRV, FTC, and TFV/TAF) were reported. |
| Percentage of Participants With Treatment Adherence of >95 (Approach 1) Through Week 96 | Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm) | Treatment adherence (defined as adherence of \>95%) was assessed by the drug accountability cumulative through Week 96 (Approach 1). |
| Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 96 | Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm) | Treatment adherence (defined as adherence of \>95%) was assessed by the drug accountability cumulative treatment adherence up to time point where not more than one bottle was missing, or if available, through Week 96, whichever came sooner (Approach 2). |
| Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96 | Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm) | AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events were symptoms causing inability to perform usual social & functional activities. Grade 4 (Life-threatening) events were symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. SAE is any 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. |
| Change From Reference in Serum Creatinine Levels at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in serum creatinine levels at Week 96 was assessed. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in eGFRcr (by Cockcroft-Gault formula) was assessed at Week 96. eGFRcr according to the Cockcroft Gault formula- Male: (140 - age in years)\*(weight in kilogram \[kg\])/72\*(serum creatinine in milligram per deciliter \[mg/dL\])=eGFRcr (milliliter per minute \[mL/min\]); Female: (140 - age in years)\*(weight in kg)/72\*(serum creatinine in mg/dL)\*0.85=eGFRcr (mL/min). For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (by CKD-EPI) at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in eGFRcr (by CKD-EPI) was assessed at Week 96. eGFRcr per CKD-EPI formula - Female: 1) Serum creatinine (Scr) less than or equal to (\<=)0.7 mg/dL: 144\*(Scr/0.7)\^-0.329\*0.993\^age; 2) Scr greater than (\>)0.7 mg/dL: 144\*(Scr/0.7)\^-1.209\*0.993\^age. Male: 1) Scr \<=0.9 mg/dL: 141\*(Scr/0.9)\^-0.411\*0.993\^age; 2) Scr \>0.9 mg/dL: 141\*(Scr/0.9)\^-1.209\*0.993\^age. . For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (by CKD-EPI) at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in eGFRcyst (by CKD-EPI) was assessed at Week 96. eGFRcyst according to the CKD-EPI formula - 1) Serum Cystatin C (Scyst) \<=0.8 mg/L: 133\*(Scyst/0.8)\^-0.499\*0.996\^age (\*0.932 if female); 2) Scyst \>0.8 mg/L: 133\*(Scyst/0.8)\^-1.328\*0.996\^age (\*0.932 if female). For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Change From Reference in UACR at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in UACR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Change From Reference in URBPCR at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in URBPCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Change From Reference in UPCR at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in UPCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Change From Reference in UB2MGCR at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in UB2MGCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Percent Change From Reference in FEPO4 at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Percent change from reference in FEPO4 at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Percent Change From Reference in Levels of Serum P1NP at Week 96 | 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 | Percent change from reference in serum P1NP levels at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Percent Change From Reference in Levels of Serum CTX at Week 96 | 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 | Percent change from reference in serum CTX at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Percent Change From Reference in Levels of PTH at Week 96 | 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 | Percent change from reference in PTH at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Percent Change From Reference in Levels of 25-OH Vitamin D at Week 96 | 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 | Percent change from reference in 25-OH Vitamin D at Week 96 were reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Percent Change From Reference in Hip and Spine BMD at Week 96 | 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 | The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by DXA 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. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
| Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=20 Copies/mL) Cumulative Through 48 Weeks | Through 48 Weeks | Virologic rebound was defined as: confirmed plasma HIV-1 RNA \>=20 copies/mL up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA \>=20 copies/mL at premature discontinuation (irrespective of reason). Percentage of participants with virologic rebound were reported. |
| Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 to end of extension (at every 6 months, up to 42 months) | Virologic rebound is defined as participants who show confirmed HIV-1 RNA \>=50 copies/mL, or for which the last available (single) HIV-1 RNA value on treatment was \>=50 copies/mL. Here, Kaplan-Meier estimates (%) of non-virologic rebound at every 6 months interval are presented. |
| Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 to end of extension (up to 42 months) | Percentage of participants with non-treatment failure by Kaplan-Meier Estimates were reported. Treatment failure was defined as having either protocol-defined virologic rebound or having discontinued for reasons other than alternate access to D/C/F/TAF (or other antiretroviral \[ARV\]). |
| Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 to end of extension (up to 42 months) | Percentage of participants with HIV RNA \<50, \<20, \<200 copies/mL post Week 96 to end of extension were reported. |
| CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 to end of extension (up to 42 months) | The immunologic change was determined by Cluster of CD4+ cell count. CD4+ cell count post-Week 96 to end of extension were assessed. |
| Percentage of Participants With Treatment Adherence of >95% From Week 96 to End of Extension | Week 96 to end of extension (up to 42 months) | Treatment adherence (defined as adherence of \>95%) was assessed by the drug accountability and was calculated cumulative 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 from Week 96 to end of extension. |
| Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Post-Week 96 to End of Extension | From Week 96 to end of extension (up to 42 months) | AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events were symptoms causing inability to perform usual social & functional activities. Grade 4 (Life-threatening) events were symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. SAE is any 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. |
| Change From Reference in BMD T-score of Hip and Spine at Week 96 | 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 | 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. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). |
Countries
Belgium, Canada, France, Poland, Puerto Rico, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) Participants received a single fixed dose combination (FDC) tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF tablet), orally once daily up to Week 48. After Week 48, all participants continued to receive D/C/F/TAF treatment (that is, initial switch to D/C/F/TAF group) up to Week 96. After Week 96, participants were given the opportunity to continue D/C/F/TAF treatment until D/C/F/TAF became commercially available up to 42 months (end of extension). | 763 |
| Control (Baseline to Switch) Participants received a boosted protease inhibitor (bPI) (limited to darunavir \[DRV\] or atazanavir with low-dose ritonavir \[rtv\] or cobicistat \[COBI\], or lopinavir with rtv) combined with emtricitabine/tenofovir disoproxil fumarate (F/TDF) up to Week 48. | 378 |
| Total | 1,141 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| BL to EOE-Test and BL to Switch-Control | Adverse Event | 24 | 4 | 0 |
| BL to EOE-Test and BL to Switch-Control | Death | 4 | 0 | 0 |
| BL to EOE-Test and BL to Switch-Control | Lost to Follow-up | 25 | 7 | 0 |
| BL to EOE-Test and BL to Switch-Control | Non-compliance with study drug | 4 | 0 | 0 |
| BL to EOE-Test and BL to Switch-Control | Other | 19 | 4 | 0 |
| BL to EOE-Test and BL to Switch-Control | Physician Decision | 4 | 0 | 0 |
| BL to EOE-Test and BL to Switch-Control | Protocol Violation | 2 | 1 | 0 |
| BL to EOE-Test and BL to Switch-Control | Randomized but not treated | 3 | 5 | 0 |
| BL to EOE-Test and BL to Switch-Control | Withdrawal by Subject | 32 | 10 | 0 |
| Switch to D/C/F/TAF (Until EOE) | Adverse Event | 0 | 0 | 11 |
| Switch to D/C/F/TAF (Until EOE) | Death | 0 | 0 | 1 |
| Switch to D/C/F/TAF (Until EOE) | Lost to Follow-up | 0 | 0 | 10 |
| Switch to D/C/F/TAF (Until EOE) | Other | 0 | 0 | 8 |
| Switch to D/C/F/TAF (Until EOE) | Physician Decision | 0 | 0 | 1 |
| Switch to D/C/F/TAF (Until EOE) | Pregnancy | 0 | 0 | 2 |
| Switch to D/C/F/TAF (Until EOE) | Withdrawal by Subject | 0 | 0 | 5 |
Baseline characteristics
| Characteristic | Control (Baseline to Switch) | Total | D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) |
|---|---|---|---|
| Age, Continuous | 44.8 years STANDARD_DEVIATION 10.77 | 45.1 years STANDARD_DEVIATION 10.83 | 45.3 years STANDARD_DEVIATION 10.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 59 Participants | 170 Participants | 111 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 317 Participants | 966 Participants | 649 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 26 Participants | 17 Participants |
| Race/Ethnicity, Customized Black or African American | 82 Participants | 237 Participants | 155 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 56 Participants | 151 Participants | 95 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 26 Participants | 20 Participants |
| Race/Ethnicity, Customized White Non-Hispanic | 225 Participants | 701 Participants | 476 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 26 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 82 Participants | 237 Participants | 155 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 8 Participants | 6 Participants |
| Race (NIH/OMB) White | 282 Participants | 855 Participants | 573 Participants |
| Region of Enrollment Belgium | 20 Participants | 52 Participants | 32 Participants |
| Region of Enrollment Canada | 21 Participants | 66 Participants | 45 Participants |
| Region of Enrollment France | 28 Participants | 97 Participants | 69 Participants |
| Region of Enrollment Poland | 35 Participants | 126 Participants | 91 Participants |
| Region of Enrollment Spain | 52 Participants | 169 Participants | 117 Participants |
| Region of Enrollment Sweden | 5 Participants | 28 Participants | 23 Participants |
| Region of Enrollment Switzerland | 13 Participants | 39 Participants | 26 Participants |
| Region of Enrollment United Kingdom | 23 Participants | 70 Participants | 47 Participants |
| Region of Enrollment United States | 181 Participants | 494 Participants | 313 Participants |
| Sex: Female, Male Female | 65 Participants | 205 Participants | 140 Participants |
| Sex: Female, Male Male | 313 Participants | 936 Participants | 623 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 763 | 0 / 378 | 1 / 352 |
| other Total, other adverse events | 584 / 763 | 222 / 378 | 213 / 352 |
| serious Total, serious adverse events | 114 / 763 | 18 / 378 | 42 / 352 |
Outcome results
Primary
Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 48
Virologic rebound was defined as: confirmed plasma human immunodeficiency virus - 1 (HIV-1) Ribonucleic Acid (RNA) level greater than or equal to (\>=)50 copies per milliliter (copies/mL) up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA \>=50 copies/mL at premature discontinuation (irrespective of reason). Percentage of participants with virologic rebound were reported.
Time frame: Through Week 48
Population: Intent-to-treat (ITT) analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 48 | 2.5 Percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 48 | 2.1 Percentage of participants |
p-value: <0.00195% CI: [-1.5, 2.2]Stratum-adjusted Mantel-Haenszel (MH)
Secondary
CD4+ Cell Count Post-Week 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.
Time frame: Week 96 to end of extension (up to 42 months)
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure and n (number analyzed) signifies participants analyzed at specified timepoints
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 30 months | 730.4 cells/mm^3 | Standard Error 23.24 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 24 months | 712.7 cells/mm^3 | Standard Error 15.98 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 12 months | 707.6 cells/mm^3 | Standard Error 11.93 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 36 months | 732.0 cells/mm^3 | Standard Error 33.1 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 6 months | 706.4 cells/mm^3 | Standard Error 10.51 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 42 months | 714.3 cells/mm^3 | Standard Error 56.26 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 18 months | 713.3 cells/mm^3 | Standard Error 12.16 |
| Control (Baseline to Switch) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 42 months | 705.6 cells/mm^3 | Standard Error 112.99 |
| Control (Baseline to Switch) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 6 months | 681.3 cells/mm^3 | Standard Error 14.99 |
| Control (Baseline to Switch) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 12 months | 676.2 cells/mm^3 | Standard Error 14.57 |
| Control (Baseline to Switch) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 18 months | 686.1 cells/mm^3 | Standard Error 17.05 |
| Control (Baseline to Switch) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 30 months | 685.8 cells/mm^3 | Standard Error 28.61 |
| Control (Baseline to Switch) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 36 months | 733.3 cells/mm^3 | Standard Error 54.73 |
| Control (Baseline to Switch) | CD4+ Cell Count Post-Week 96 to End of Extension | Week 96 + 24 months | 686.4 cells/mm^3 | Standard Error 21.2 |
Secondary
Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48
Change from baseline in spine, hip, and femoral neck BMD T-Score was assessed at Week 24 and 48. T-score values \>= -1.0 were considered normal, T-score values \< -1.0 to -2.5 indicate osteopenia and T-score values \< -2.5 indicate osteoporosis.
Time frame: Baseline, Weeks 24 and 48
Population: The bone investigation substudy (BIS) analysis set included all participants who were randomized and received at least 1 dose of study drug in the study, and had at least one postbaseline value for BMD data. Here 'n' specifies those participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Spine BMD T-score: Change at Week 24 | 0.102 Units on a scale | Standard Error 0.0172 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Hip BMD T-score: Change at Week 48 | 0.095 Units on a scale | Standard Error 0.0122 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Hip BMD T-score: Baseline | -0.575 Units on a scale | Standard Error 0.0643 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Femoral Neck BMD T-score: Baseline | -0.782 Units on a scale | Standard Error 0.0625 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Spine BMD T-score: Change at Week 48 | 0.132 Units on a scale | Standard Error 0.0217 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Femoral Neck BMD T-score: Change at Week 24 | 0.019 Units on a scale | Standard Error 0.0128 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Hip BMD T-score: Change at Week 24 | 0.037 Units on a scale | Standard Error 0.0108 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Femoral Neck BMD T-score: Change at Week 48 | 0.039 Units on a scale | Standard Error 0.0146 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Spine BMD T-score: Baseline | -0.713 Units on a scale | Standard Error 0.085 |
| Control (Baseline to Switch) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Femoral Neck BMD T-score: Change at Week 48 | -0.039 Units on a scale | Standard Error 0.0214 |
| Control (Baseline to Switch) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Spine BMD T-score: Baseline | -0.467 Units on a scale | Standard Error 0.126 |
| Control (Baseline to Switch) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Spine BMD T-score: Change at Week 24 | -0.033 Units on a scale | Standard Error 0.0253 |
| Control (Baseline to Switch) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Spine BMD T-score: Change at Week 48 | -0.063 Units on a scale | Standard Error 0.0264 |
| Control (Baseline to Switch) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Hip BMD T-score: Baseline | -0.484 Units on a scale | Standard Error 0.0839 |
| Control (Baseline to Switch) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Hip BMD T-score: Change at Week 24 | -0.024 Units on a scale | Standard Error 0.0144 |
| Control (Baseline to Switch) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Hip BMD T-score: Change at Week 48 | -0.016 Units on a scale | Standard Error 0.0139 |
| Control (Baseline to Switch) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Femoral Neck BMD T-score: Baseline | -0.699 Units on a scale | Standard Error 0.0899 |
| Control (Baseline to Switch) | Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | Femoral Neck BMD T-score: Change at Week 24 | -0.044 Units on a scale | Standard Error 0.0183 |
Secondary
Change From Baseline in Cluster of Differentiation 4 Plus (CD4+) Cell Count at Weeks 24 and 48
Change from baseline in CD4+ cell count was assessed at Weeks 24 and 48.
Time frame: Baseline, Weeks 24 and 48
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here 'n' specifies those participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Cluster of Differentiation 4 Plus (CD4+) Cell Count at Weeks 24 and 48 | Change at Week 48 | 21.0 Cells per cubic millimeter (cells/mm^3) | Standard Error 5.97 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Cluster of Differentiation 4 Plus (CD4+) Cell Count at Weeks 24 and 48 | Baseline | 653.3 Cells per cubic millimeter (cells/mm^3) | Standard Error 9.12 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Cluster of Differentiation 4 Plus (CD4+) Cell Count at Weeks 24 and 48 | Change at Week 24 | 14.3 Cells per cubic millimeter (cells/mm^3) | Standard Error 5.99 |
| Control (Baseline to Switch) | Change From Baseline in Cluster of Differentiation 4 Plus (CD4+) Cell Count at Weeks 24 and 48 | Change at Week 24 | 8.5 Cells per cubic millimeter (cells/mm^3) | Standard Error 7.76 |
| Control (Baseline to Switch) | Change From Baseline in Cluster of Differentiation 4 Plus (CD4+) Cell Count at Weeks 24 and 48 | Change at Week 48 | 9.1 Cells per cubic millimeter (cells/mm^3) | Standard Error 8.41 |
| Control (Baseline to Switch) | Change From Baseline in Cluster of Differentiation 4 Plus (CD4+) Cell Count at Weeks 24 and 48 | Baseline | 641.7 Cells per cubic millimeter (cells/mm^3) | Standard Error 13.15 |
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48
Change from baseline in eGFRcr (by CKD-EPI) was assessed at Weeks 24 and 48. eGFRcr per CKD-EPI formula - Female: 1) Serum creatinine (Scr) less than or equal to (\<=)0.7 mg/dL: 144\*(Scr/0.7)\^-0.329\*0.993age; 2) Scr greater than (\>)0.7 mg/dL: 144\*(Scr/0.7)\^-1.209\*0.993age. Male: 1) Scr \<=0.9 mg/dL: 141\*(Scr/0.9)\^-0.411\*0.993age; 2) Scr \>0.9 mg/dL: 141\*(Scr/0.9)\^-1.209\*0.993age.
Time frame: Baseline, Weeks 24 and 48
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here, N (number of participants analyzed) indicates number of participants evaluable for this endpoint; and 'n' specifies those participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 | Change at Week 24 | -1.67 mL/min/1.73 m^2 | Standard Error 0.359 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 | Change at Week 48 | -1.97 mL/min/1.73 m^2 | Standard Error 0.369 |
| Control (Baseline to Switch) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 | Change at Week 48 | -0.88 mL/min/1.73 m^2 | Standard Error 0.531 |
| Control (Baseline to Switch) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 | Change at Week 24 | -0.75 mL/min/1.73 m^2 | Standard Error 0.51 |
Comparison: Change at Week 24p-value: =0.14395% CI: [-2.14, 0.31]ANCOVA
Comparison: Change at Week 48p-value: =0.09295% CI: [-2.36, 0.18]ANCOVA
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Weeks 24 and 48
Change from baseline in eGFRcr (by Cockcroft-Gault formula) was assessed at Weeks 24 and 48. eGFRcr according to the Cockcroft Gault formula- Male: (140 - age in years)\*(weight in kilogram \[kg\])/72\*(serum creatinine in milligram per deciliter \[mg/dL\])=eGFRcr (milliliter per minute \[mL/min\]); Female: (140 - age in years)\*(weight in kg)/72\*(serum creatinine in mg/dL)\*0.85=eGFRcr (mL/min).
Time frame: Baseline, Weeks 24 and 48
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here, N (number of participants analyzed) indicates number of participants evaluable for this endpoint; and 'n' specifies those participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Weeks 24 and 48 | Change at Week 24 | -0.38 milliliter per minute (mL/min) | Standard Error 0.502 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Weeks 24 and 48 | Change at Week 48 | -0.94 milliliter per minute (mL/min) | Standard Error 0.492 |
| Control (Baseline to Switch) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Weeks 24 and 48 | Change at Week 24 | 0.20 milliliter per minute (mL/min) | Standard Error 0.715 |
| Control (Baseline to Switch) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Weeks 24 and 48 | Change at Week 48 | -0.20 milliliter per minute (mL/min) | Standard Error 0.708 |
Comparison: Change at Week 24p-value: =0.50695% CI: [-2.3, 1.13]ANCOVA
Comparison: Change Week 48p-value: =0.39295% CI: [-2.43, 0.95]ANCOVA
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48
Change from baseline in eGFRcyst (by CKD-EPI) was assessed at Weeks 24 and 48. eGFRcyst according to the CKD-EPI formula - 1) Serum Cystatin C (Scyst) \<=0.8 mg/L: 133\*(Scyst/0.8)\^-0.499\*0.996age (\*0.932 if female); 2) Scyst \>0.8 mg/L: 133\*(Scyst/0.8)\^-1.328\*0.996age (\*0.932 if female).
Time frame: Baseline, Weeks 24 and 48
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here, 'n' specifies those participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 | eGFRcyst: Change at Week 24 | 0.21 mL/min/1.73 m^2 | Standard Error 0.338 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 | eGFRcyst: Change at Week 48 | -0.42 mL/min/1.73 m^2 | Standard Error 0.36 |
| Control (Baseline to Switch) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 | eGFRcyst: Change at Week 24 | -0.93 mL/min/1.73 m^2 | Standard Error 0.483 |
| Control (Baseline to Switch) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 | eGFRcyst: Change at Week 48 | -1.76 mL/min/1.73 m^2 | Standard Error 0.517 |
Comparison: Change at Week 24p-value: =0.05495% CI: [-0.02, 2.29]ANCOVA
Comparison: Change at Week 48p-value: =0.03495% CI: [0.1, 2.57]ANCOVA
Secondary
Change From Baseline in Serum Creatinine Levels at Weeks 24 and 48
Change from baseline in serum creatinine levels at Weeks 24 and 48 was assessed.
Time frame: Baseline and Weeks 24 and 48
Population: ITT analysis set included all participants randomized and received at least 1 dose of study treatment. Here, N (number of participants analyzed) indicates number of participants evaluable for this endpoint; and 'n' specifies participants analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Serum Creatinine Levels at Weeks 24 and 48 | Change at Week 24 | 1.22 micro mole per liter | Standard Error 0.358 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Serum Creatinine Levels at Weeks 24 and 48 | Change at Week 48 | 1.27 micro mole per liter | Standard Error 0.368 |
| Control (Baseline to Switch) | Change From Baseline in Serum Creatinine Levels at Weeks 24 and 48 | Change at Week 24 | 0.88 micro mole per liter | Standard Error 0.509 |
| Control (Baseline to Switch) | Change From Baseline in Serum Creatinine Levels at Weeks 24 and 48 | Change at Week 48 | 0.65 micro mole per liter | Standard Error 0.53 |
Comparison: Change at Week 24p-value: =0.5895% CI: [-0.88, 1.57]ANCOVA
Comparison: Change at Week 48p-value: =0.3495% CI: [-0.65, 1.88]ANCOVA
Secondary
Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48
Change from baseline in UACR and UPCR was assessed at Weeks 24 and 48. Lower levels of albumin or protein in the urine indicates better proximal tubular function.
Time frame: Baseline, Weeks 24 and 48
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here, N (number of participants analyzed) indicates number of participants evaluable for this endpoint; and 'n' specifies those participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | UACR: Baseline | 6.20 milligram per gram (mg/g) |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | UACR: Change at Week 24 | -0.78 milligram per gram (mg/g) |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | UACR: Change at Week 48 | -0.76 milligram per gram (mg/g) |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | UPCR: Baseline | 61.56 milligram per gram (mg/g) |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | UPCR: Change at Week 24 | -14.63 milligram per gram (mg/g) |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | UPCR: Change at Week 48 | -22.25 milligram per gram (mg/g) |
| Control (Baseline to Switch) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | UPCR: Change at Week 24 | 0.07 milligram per gram (mg/g) |
| Control (Baseline to Switch) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | UACR: Baseline | 7.14 milligram per gram (mg/g) |
| Control (Baseline to Switch) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | UPCR: Baseline | 62.90 milligram per gram (mg/g) |
| Control (Baseline to Switch) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | UACR: Change at Week 24 | 0.44 milligram per gram (mg/g) |
| Control (Baseline to Switch) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | UPCR: Change at Week 48 | -7.37 milligram per gram (mg/g) |
| Control (Baseline to Switch) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | UACR: Change at Week 48 | 0.40 milligram per gram (mg/g) |
Comparison: UACR - Change at Week 24p-value: <0.001Van Elteren Test
Comparison: UACR - Change at Week 48p-value: <0.001Van Elteren Test
Comparison: UPCR - Change at Week 24p-value: <0.001Van Elteren Test
Comparison: UPCR - Change at Week 48p-value: <0.001Van Elteren Test
Secondary
Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48
Change from baseline in URBPCR and UB2MGCR was assessed at Weeks 24 and 48. Retinol binding protein is a marker of proximal tubular function.
Time frame: Baseline, Weeks 24 and 48
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here, N (number of participants analyzed) indicates number of participants evaluable for this endpoint; and 'n' specifies those participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | URBPCR: Baseline | 126.19 microgram per gram (mcg/g) |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | URBPCR: Change at Week 24 | -30.27 microgram per gram (mcg/g) |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | URBPCR: Change at Week 48 | -27.09 microgram per gram (mcg/g) |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | UB2MGCR: Baseline | 156.85 microgram per gram (mcg/g) |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | UB2MGCR: Change at Week 24 | -72.64 microgram per gram (mcg/g) |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | UB2MGCR: Change at Week 48 | -67.02 microgram per gram (mcg/g) |
| Control (Baseline to Switch) | Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | UB2MGCR: Change at Week 48 | 20.24 microgram per gram (mcg/g) |
| Control (Baseline to Switch) | Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | URBPCR: Baseline | 137.16 microgram per gram (mcg/g) |
| Control (Baseline to Switch) | Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | UB2MGCR: Baseline | 172.25 microgram per gram (mcg/g) |
| Control (Baseline to Switch) | Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | URBPCR: Change at Week 24 | 7.76 microgram per gram (mcg/g) |
| Control (Baseline to Switch) | Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | UB2MGCR: Change at Week 24 | 12.08 microgram per gram (mcg/g) |
| Control (Baseline to Switch) | Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | URBPCR: Change at Week 48 | 19.66 microgram per gram (mcg/g) |
Comparison: URBPCR: Change at Week 24p-value: <0.001Van Elteren Test
Comparison: URBPCR: Change at Week 48p-value: <0.001Van Elteren Test
Comparison: UB2MGCR: Change at Week 24p-value: <0.001Van Elteren Test
Comparison: UB2MGCR: Change at Week 48p-value: <0.001Van Elteren Test
Secondary
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. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: 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
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of participants analyzed) indicates number of participants evaluable for this outcome measure; and 'n' specifies participants analyzed for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Reference in BMD T-score of Hip and Spine at Week 96 | Hip region BMD | 0.122 units on a scale | Standard Error 0.0154 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Reference in BMD T-score of Hip and Spine at Week 96 | Spine region BMD | 0.176 units on a scale | Standard Error 0.0259 |
| Control (Baseline to Switch) | Change From Reference in BMD T-score of Hip and Spine at Week 96 | Hip region BMD | 0.077 units on a scale | Standard Error 0.023 |
| Control (Baseline to Switch) | Change From Reference in BMD T-score of Hip and Spine at Week 96 | Spine region BMD | 0.255 units on a scale | Standard Error 0.0339 |
Secondary
Change From Reference in CD4+ Cell Count at Week 96
Change from reference in CD4+ cell count was assessed at Week 96. The change from reference in CD4+ count at a given time point is defined as: CD4+ at a given time point minus reference CD4+. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF (Comprising 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52])
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Based on non-completing=failure (NC=F) analysis with values after discontinuation imputed with the reference value. Other (intermittent) missing values are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Reference in CD4+ Cell Count at Week 96 | 32.07 cells per cubic millimeter (cells/mm^3) | Standard Error 8 |
| Control (Baseline to Switch) | Change From Reference in CD4+ Cell Count at Week 96 | 13.07 cells per cubic millimeter (cells/mm^3) | Standard Error 10.7 |
Secondary
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (by CKD-EPI) at Week 96
Change from reference in eGFRcr (by CKD-EPI) was assessed at Week 96. eGFRcr per CKD-EPI formula - Female: 1) Serum creatinine (Scr) less than or equal to (\<=)0.7 mg/dL: 144\*(Scr/0.7)\^-0.329\*0.993\^age; 2) Scr greater than (\>)0.7 mg/dL: 144\*(Scr/0.7)\^-1.209\*0.993\^age. Male: 1) Scr \<=0.9 mg/dL: 141\*(Scr/0.9)\^-0.411\*0.993\^age; 2) Scr \>0.9 mg/dL: 141\*(Scr/0.9)\^-1.209\*0.993\^age. . For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and participants at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (by CKD-EPI) at Week 96 | -1.3 mL/min/1.73 m^2 |
| Control (Baseline to Switch) | Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (by CKD-EPI) at Week 96 | -0.7 mL/min/1.73 m^2 |
Secondary
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Week 96
Change from reference in eGFRcr (by Cockcroft-Gault formula) was assessed at Week 96. eGFRcr according to the Cockcroft Gault formula- Male: (140 - age in years)\*(weight in kilogram \[kg\])/72\*(serum creatinine in milligram per deciliter \[mg/dL\])=eGFRcr (milliliter per minute \[mL/min\]); Female: (140 - age in years)\*(weight in kg)/72\*(serum creatinine in mg/dL)\*0.85=eGFRcr (mL/min). For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Week 96 | -0.9 milliliter per minute (mL/min) |
| Control (Baseline to Switch) | Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Week 96 | 0.0 milliliter per minute (mL/min) |
Secondary
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (by CKD-EPI) at Week 96
Change from reference in eGFRcyst (by CKD-EPI) was assessed at Week 96. eGFRcyst according to the CKD-EPI formula - 1) Serum Cystatin C (Scyst) \<=0.8 mg/L: 133\*(Scyst/0.8)\^-0.499\*0.996\^age (\*0.932 if female); 2) Scyst \>0.8 mg/L: 133\*(Scyst/0.8)\^-1.328\*0.996\^age (\*0.932 if female). For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and participants at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (by CKD-EPI) at Week 96 | -0.9 mL/min/1.73 m^2 |
| Control (Baseline to Switch) | Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (by CKD-EPI) at Week 96 | 1.0 mL/min/1.73 m^2 |
Secondary
Change From Reference in Serum Creatinine Levels at Week 96
Change from reference in serum creatinine levels at Week 96 was assessed. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Reference in Serum Creatinine Levels at Week 96 | 0.0 micro mole per liter |
| Control (Baseline to Switch) | Change From Reference in Serum Creatinine Levels at Week 96 | 0.0 micro mole per liter |
Secondary
Change From Reference in UACR at Week 96
Change from reference in UACR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Reference in UACR at Week 96 | -0.63 milligram per gram (mg/g) |
| Control (Baseline to Switch) | Change From Reference in UACR at Week 96 | -0.93 milligram per gram (mg/g) |
Secondary
Change From Reference in UB2MGCR at Week 96
Change from reference in UB2MGCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Reference in UB2MGCR at Week 96 | -68.22 microgram per gram (mcg/g) |
| Control (Baseline to Switch) | Change From Reference in UB2MGCR at Week 96 | -110.31 microgram per gram (mcg/g) |
Secondary
Change From Reference in UPCR at Week 96
Change from reference in UPCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Reference in UPCR at Week 96 | -22.23 milligram per gram (mg/g) |
| Control (Baseline to Switch) | Change From Reference in UPCR at Week 96 | -12.81 milligram per gram (mg/g) |
Secondary
Change From Reference in URBPCR at Week 96
Change from reference in URBPCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Change From Reference in URBPCR at Week 96 | -25.08 microgram per gram (mcg/g) |
| Control (Baseline to Switch) | Change From Reference in URBPCR at Week 96 | -39.07 microgram per gram (mcg/g) |
Secondary
Number of Participants With Resistance to Study Drug
HIV-1 genotypes were analyzed from samples of participants with confirmed virologic rebound (virologic rebound was defined as: confirmed HIV-1 RNA \>=50 copies/mL up to, and including the upper bound of the Week 48 window) and with HIV-1 RNA value \>=400 copies/mL or who discontinued with last HIV-1 RNA \>=400 copies/mL. Number of participants who developed resistance to any of the study drug was determined.
Time frame: Up to Week 48
Population: The ITT population with confirmed virologic rebound and with HIV-1 RNA value \>=400 copies/mL was analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Number of Participants With Resistance to Study Drug | 1 Participants |
| Control (Baseline to Switch) | Number of Participants With Resistance to Study Drug | 3 Participants |
Secondary
Number of Participants With Resistance to Study Drug Through Week 96
HIV-1 genotypes were analyzed from samples of participants with confirmed virologic rebound in case they had HIV-1 RNA values \>=400 copies/mL at failure or at later time points, including participants who discontinued with last HIV-1 RNA \>=400 copies/mL. Virologic rebound was defined as: confirmed plasma HIV-1 RNA level \>=20 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA \>=20 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA \>=20 copies/mL at the study cutoff of Week 96 (that is, any last viral load \[re\]test having occurred no later than 6 weeks after Week 96). Number of participants who developed resistance to any of the study drug (DRV, FTC, and TFV/TAF) were reported.
Time frame: Through Week 96 (D/C/F/TAF arm), up to Week 48 (Control arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies total number of participants with screening/baseline and endpoint genotype. Due to the low proportion of rebounders of which the majority had low viral load values, few samples were eligible for postbaseline genotyping.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Number of Participants With Resistance to Study Drug Through Week 96 | FTC RAMs | 0 Participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Number of Participants With Resistance to Study Drug Through Week 96 | DRV resistance-associated mutations (RAMs) | 0 Participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Number of Participants With Resistance to Study Drug Through Week 96 | TFV RAMs | 0 Participants |
| Control (Baseline to Switch) | Number of Participants With Resistance to Study Drug Through Week 96 | TFV RAMs | 0 Participants |
| Control (Baseline to Switch) | Number of Participants With Resistance to Study Drug Through Week 96 | FTC RAMs | 0 Participants |
| Control (Baseline to Switch) | Number of Participants With Resistance to Study Drug Through Week 96 | DRV resistance-associated mutations (RAMs) | 0 Participants |
| Switch to D/C/F/TAF | Number of Participants With Resistance to Study Drug Through Week 96 | DRV resistance-associated mutations (RAMs) | 0 Participants |
| Switch to D/C/F/TAF | Number of Participants With Resistance to Study Drug Through Week 96 | FTC RAMs | 1 Participants |
| Switch to D/C/F/TAF | Number of Participants With Resistance to Study Drug Through Week 96 | TFV RAMs | 0 Participants |
Secondary
Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48
An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events were symptoms causing inability to perform usual social & functional activities. Grade 4 (Life-threatening) events were symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death.
Time frame: Up to Week 48
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48 | Grade 3 AEs | 5.6 Percentage of Participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48 | Grade 4 AEs | 1.2 Percentage of Participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48 | SAEs | 4.6 Percentage of Participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48 | Premature discontinuations due to AEs | 1.4 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48 | Premature discontinuations due to AEs | 1.3 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48 | Grade 3 AEs | 6.3 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48 | SAEs | 4.8 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48 | Grade 4 AEs | 1.9 Percentage of Participants |
Secondary
Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs 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. Grade 3 (Severe) events were symptoms causing inability to perform usual social & functional activities. Grade 4 (Life-threatening) events were symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. SAE is any 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.
Time frame: From Week 96 to end of extension (up to 42 months)
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Post-Week 96 to End of Extension | Grade 3 AEs | 5.7 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Post-Week 96 to End of Extension | Grade 4 AEs | 2.1 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Post-Week 96 to End of Extension | SAEs | 7.3 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Post-Week 96 to End of Extension | Premature discontinuations due to AEs | 1.1 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Post-Week 96 to End of Extension | Premature discontinuations due to AEs | 2.1 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Post-Week 96 to End of Extension | Grade 3 AEs | 5.0 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Post-Week 96 to End of Extension | SAEs | 7.7 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Post-Week 96 to End of Extension | Grade 4 AEs | 1.5 percentage of participants |
Secondary
Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96
AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events were symptoms causing inability to perform usual social & functional activities. Grade 4 (Life-threatening) events were symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. SAE is any 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.
Time frame: Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96 | Grade 3 AEs | 10.5 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96 | Grade 4 AEs | 2.4 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96 | SAEs | 8.7 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96 | Premature discontinuations due to AEs | 2.2 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96 | Premature discontinuations due to AEs | 2.0 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96 | Grade 3 AEs | 6.3 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96 | SAEs | 6.0 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96 | Grade 4 AEs | 1.1 percentage of participants |
Secondary
Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension
Percentage of participants with HIV RNA \<50, \<20, \<200 copies/mL post Week 96 to end of extension were reported.
Time frame: Week 96 to end of extension (up to 42 months)
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) indicates number of participants evaluable for this outcome measure and 'n' specifies participants analyzed for specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 6 months (<50 copies/mL) | 97.8 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 12 months (<200 copies/mL) | 99.3 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 18 months (<200 copies/mL) | 100 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 24 months (<50 copies/mL) | 99.3 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 24 months (<200 copies/mL) | 99.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 42 months (<200 copies/mL) | 100 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 30 months (<200 copies/mL) | 100 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 6 months (<20 copies/mL) | 91.4 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 30 months (<50 copies/mL) | 99.3 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 12 months (<20 copies/mL) | 93.9 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 12 months (<50 copies/mL) | 98.4 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 18 months (<20 copies/mL) | 96.1 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 36 months (<50 copies/mL) | 98.1 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 24 months (<20 copies/mL) | 96.1 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 36 months (<200 copies/mL) | 100 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 30 months (<20 copies/mL) | 95.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 42 months (<50 copies/mL) | 100 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 36 months (<20 copies/mL) | 94.2 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 18 months (<50 copies/mL) | 99.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 42 months (<20 copies/mL) | 93.8 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 6 months (<200 copies/mL) | 99.1 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 42 months (<20 copies/mL) | 100 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 30 months (<200 copies/mL) | 100 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 36 months (<200 copies/mL) | 100 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 42 months (<200 copies/mL) | 100 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 6 months (<50 copies/mL) | 97.9 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 12 months (<50 copies/mL) | 97.4 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 18 months (<50 copies/mL) | 98.7 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 24 months (<50 copies/mL) | 98.5 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 30 months (<50 copies/mL) | 100 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 36 months (<50 copies/mL) | 100 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 42 months (<50 copies/mL) | 100 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 6 months (<200 copies/mL) | 99.7 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 18 months (<200 copies/mL) | 99.1 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 24 months (<200 copies/mL) | 99.3 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 6 months (<20 copies/mL) | 93.4 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 12 months (<20 copies/mL) | 91.4 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 18 months (<20 copies/mL) | 92.9 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 24 months (<20 copies/mL) | 95.5 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 30 months (<20 copies/mL) | 92.2 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 36 months (<20 copies/mL) | 96.2 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension | Week 96 + 12 months (<200 copies/mL) | 98.7 percentage of participants |
Secondary
Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates
Percentage of participants with non-treatment failure by Kaplan-Meier Estimates were reported. Treatment failure was defined as having either protocol-defined virologic rebound or having discontinued for reasons other than alternate access to D/C/F/TAF (or other antiretroviral \[ARV\]).
Time frame: Week 96 to end of extension (up to 42 months)
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment. Here, N (number of participants analyzed) indicates number of participants evaluable for this outcome measure; and 'n' specifies participants analyzed for specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 36 months | 84.9 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 | 100 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 6 months | 98.1 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 12 months | 94.3 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 18 months | 91.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 24 months | 89.4 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 30 months | 87.0 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 42 months | 81.7 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 36 months | 82.6 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 24 months | 89.7 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 | 100 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 18 months | 92.2 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 6 months | 98.5 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 30 months | 88.1 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates | Week 96 + 12 months | 95.4 percentage of participants |
Secondary
Percentage of Participants With Non-Virologic Rebound at Week 48 by Kaplan-Meier Estimates
Virologic rebound was defined as: confirmed plasma HIV-1 RNA \>=50 copies/mL up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA \>=50 copies/mL at premature discontinuation (irrespective of reason). Here Kaplan-Meier estimates percentage of participants with non-virologic rebound at week 48.
Time frame: Baseline up to Week 48
Population: ITT analysis set included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Virologic Rebound at Week 48 by Kaplan-Meier Estimates | 97.7 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Virologic Rebound at Week 48 by Kaplan-Meier Estimates | 97.8 percentage of participants |
Secondary
Percentage of Participants With Non-Virologic Rebound at Week 96 by Kaplan-Meier Estimates
Here Kaplan-Meier estimates percentage of participants with non-virologic rebound at Week 96.
Time frame: Baseline to Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Virologic Rebound at Week 96 by Kaplan-Meier Estimates | 96.7 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Virologic Rebound at Week 96 by Kaplan-Meier Estimates | 97.8 percentage of participants |
Secondary
Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates
Virologic rebound is defined as participants who show confirmed HIV-1 RNA \>=50 copies/mL, or for which the last available (single) HIV-1 RNA value on treatment was \>=50 copies/mL. Here, Kaplan-Meier estimates (%) of non-virologic rebound at every 6 months interval are presented.
Time frame: Week 96 to end of extension (at every 6 months, up to 42 months)
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here, N (number of participants analyzed) indicates number of participants evaluable for this outcome measure; and 'n' specifies participants analyzed for specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 | 100 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 6 months | 99.4 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 12 months | 98.0 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 18 months | 97.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 24 months | 97.1 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 30 months | 95.3 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 36 months | 92.4 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 42 months | 92.4 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 | 100 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 30 months | 96.5 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 6 months | 100 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 24 months | 96.5 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 12 months | 98.5 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 36 months | 96.5 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates | Week 96 + 18 months | 98.1 percentage of participants |
Secondary
Percentage of Participants With Treatment Adherence of >95 (Approach 1) Through Week 96
Treatment adherence (defined as adherence of \>95%) was assessed by the drug accountability cumulative through Week 96 (Approach 1).
Time frame: Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here, N (number of participants analyzed) indicates the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Treatment Adherence of >95 (Approach 1) Through Week 96 | 91.6 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Treatment Adherence of >95 (Approach 1) Through Week 96 | 87.3 percentage of participants |
Secondary
Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 48
Treatment adherence (defined as adherence of \>95%) was assessed by the drug accountability cumulative treatment adherence up to time point where not more than one bottle was missing, or if available, through Week 48, whichever came sooner (Approach 2).
Time frame: Through Week 48
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here, 'N' (number of participants analyzed) indicates the number of participants evaluable for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 48 | 82.7 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 48 | 77.2 percentage of participants |
Secondary
Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 96
Treatment adherence (defined as adherence of \>95%) was assessed by the drug accountability cumulative treatment adherence up to time point where not more than one bottle was missing, or if available, through Week 96, whichever came sooner (Approach 2).
Time frame: Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here, 'N' (number of participants analyzed) indicates the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 96 | 82.8 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 96 | 80.9 percentage of participants |
Secondary
Percentage of Participants With Treatment Adherence of >95% From Week 96 to End of Extension
Treatment adherence (defined as adherence of \>95%) was assessed by the drug accountability and was calculated cumulative 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 from Week 96 to end of extension.
Time frame: Week 96 to end of extension (up to 42 months)
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here, N (number of participants analyzed) indicates the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Treatment Adherence of >95% From Week 96 to End of Extension | 89.5 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Treatment Adherence of >95% From Week 96 to End of Extension | 89.4 percentage of participants |
Secondary
Percentage of Participants With Treatment Adherence of Greater Than (>)95 Percent (%) (Approach 1) Through Week 48
Treatment adherence (defined as adherence of \>95%) was assessed by the drug accountability cumulative through Week 48 (Approach 1).
Time frame: Through Week 48
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here, N (number of participants analyzed) indicates the number of participants evaluable for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Treatment Adherence of Greater Than (>)95 Percent (%) (Approach 1) Through Week 48 | 91.6 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants With Treatment Adherence of Greater Than (>)95 Percent (%) (Approach 1) Through Week 48 | 85.3 Percentage of Participants |
Secondary
Percentage of Participants With Virologic Failure Based on HIV-1 RNA >=20, >=50, and >=200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach
Percentage of participants with virologic failure based on HIV-1 RNA \>=20, \>=50, and \>=200 copies/mL threshold were analyzed at Week 96 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic failure was defined by the FDA snapshot approach as having last available HIV-1 RNA \>=20/50/200 copies/mL at Week 96; virologic failure - leading to discontinuation; virologic failure - discontinued due to other reason and last available HIV-1 RNA \>=20/50/200 copies/mL.
Time frame: Week 96 (Comprising up to Week 96 for D/C/F/TAF and 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52 up to Week 96])
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Failure Based on HIV-1 RNA >=20, >=50, and >=200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | >=20 copies/mL | 6.8 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Failure Based on HIV-1 RNA >=20, >=50, and >=200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | >=50 copies/mL | 1.2 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Failure Based on HIV-1 RNA >=20, >=50, and >=200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | >=200 copies/mL | 0.3 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Failure Based on HIV-1 RNA >=20, >=50, and >=200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | >=20 copies/mL | 6.0 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Failure Based on HIV-1 RNA >=20, >=50, and >=200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | >=50 copies/mL | 1.7 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Failure Based on HIV-1 RNA >=20, >=50, and >=200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | >=200 copies/mL | 0 percentage of participants |
Secondary
Percentage of Participants With Virologic Rebound (HIV-1 RNA >=200 Copies/mL) Cumulative Through Week 96
Virologic rebound was defined as: confirmed plasma HIV-1 RNA level \>=200 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA \>=200 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA \>=200 copies/mL at the study cutoff of Week 96 (that is, any last viral load \[re\]test having occurred no later than 6 weeks after Week 96). Percentage of participants with virologic rebound were reported.
Time frame: Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Population: Intent-to-treat (ITT) analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Rebound (HIV-1 RNA >=200 Copies/mL) Cumulative Through Week 96 | 0.5 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Rebound (HIV-1 RNA >=200 Copies/mL) Cumulative Through Week 96 | 0.6 percentage of participants |
Secondary
Percentage of Participants With Virologic Rebound (HIV-1 RNA >=20 Copies/mL) Cumulative Through Week 96
Virologic rebound was defined as: confirmed plasma HIV-1 RNA level \>=20 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA \>=20 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA \>=20 copies/mL at the study cutoff of Week 96 (that is, any last viral load \[re\]test having occurred no later than 6 weeks after Week 96). Percentage of participants with virologic rebound were reported.
Time frame: Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Population: Intent-to-treat (ITT) analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Rebound (HIV-1 RNA >=20 Copies/mL) Cumulative Through Week 96 | 13.8 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Rebound (HIV-1 RNA >=20 Copies/mL) Cumulative Through Week 96 | 8.8 percentage of participants |
Secondary
Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 96
Virologic rebound was defined as: confirmed plasma HIV-1 RNA level \>=50 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA \>=50 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA \>=50copies/mL at the study cutoff of Week 96 (that is, any last viral load \[re\]test having occurred no later than 6 weeks after Week 96). Percentage of participants with virologic rebound were reported.
Time frame: Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Population: Intent-to-treat (ITT) analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 96 | 3.1 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 96 | 2.3 percentage of participants |
Secondary
Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=200 Copies/mL) Cumulative Through 48 Weeks
Virologic rebound was defined as: confirmed plasma HIV-1 RNA \>=200 copies/mL up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA \>=200 copies/mL at premature discontinuation (irrespective of reason). Percentage of participants with virologic rebound were reported.
Time frame: Through 48 Weeks
Population: ITT analysis set included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=200 Copies/mL) Cumulative Through 48 Weeks | 0.4 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=200 Copies/mL) Cumulative Through 48 Weeks | 0.0 Percentage of Participants |
Secondary
Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=20 Copies/mL) Cumulative Through 48 Weeks
Virologic rebound was defined as: confirmed plasma HIV-1 RNA \>=20 copies/mL up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA \>=20 copies/mL at premature discontinuation (irrespective of reason). Percentage of participants with virologic rebound were reported.
Time frame: Through 48 Weeks
Population: ITT analysis set included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=20 Copies/mL) Cumulative Through 48 Weeks | 10.5 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=20 Copies/mL) Cumulative Through 48 Weeks | 11.4 Percentage of Participants |
Secondary
Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Percentage of participants with virologic response based on HIV-1 RNA \<20, \<50, and \<200 copies/mL threshold were analyzed at Week 48 using TLOVR algorithm approach. TLOVR was defined as sustained HIV-1 RNA \<20/50/200 copies/mL.
Time frame: Week 48
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | <20 copies/mL | 86.0 Percentage of Participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | <50 copies/mL | 93.7 Percentage of Participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | <200 copies/mL | 95.4 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | <20 copies/mL | 83.6 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | <50 copies/mL | 92.9 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | <200 copies/mL | 94.7 Percentage of Participants |
Secondary
Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach
Percentage of participants with virologic response based on HIV-1 RNA \<20, \<50, and \<200 copies/mL threshold were analyzed at Week 96 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic response was defined as having last available HIV-1 RNA \<20/50/200 copies/mL (observed case).
Time frame: Week 96 (Comprising up to Week 96 for D/C/F/TAF and 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52 up to Week 96])
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | <20 copies/mL | 85.3 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | <50 copies/mL | 90.7 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | <200 copies/mL | 91.2 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | <50 copies/mL | 93.8 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | <20 copies/mL | 89.8 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach | <200 copies/mL | 95.5 percentage of participants |
Secondary
Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the TLOVR Algorithm
Percentage of participants with virologic response based on HIV-1 RNA \<20, \<50, and \<200 copies/mL threshold were analyzed at Week 96 using TLOVR algorithm approach. TLOVR was defined as sustained HIV-1 RNA \<20/50/200 copies/mL.
Time frame: Week 96 (Comprising up to Week 96 for D/C/F/TAF and 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52 up to Week 96])
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the TLOVR Algorithm | <20 copies/mL | 79.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the TLOVR Algorithm | <50 copies/mL | 89.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the TLOVR Algorithm | <200 copies/mL | 91.7 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the TLOVR Algorithm | <20 copies/mL | 88.1 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the TLOVR Algorithm | <50 copies/mL | 94.3 percentage of participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the TLOVR Algorithm | <200 copies/mL | 95.7 percentage of participants |
Secondary
Percentage of Participants With Virologic Response Based on HIV-1 RNA Less Than (<)20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Food and Drug Administration (FDA) Snapshot Approach
Percentage of participants with virologic response based on HIV-1 RNA \<20, \<50, and \<200 copies/mL threshold were analyzed at Week 48 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic response was defined as HIV-1 RNA \<20/50/200 copies/mL (observed case).
Time frame: Week 48
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Response Based on HIV-1 RNA Less Than (<)20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Food and Drug Administration (FDA) Snapshot Approach | <50 copies/mL | 94.9 Percentage of Participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Response Based on HIV-1 RNA Less Than (<)20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Food and Drug Administration (FDA) Snapshot Approach | <200 copies/mL | 95.0 Percentage of Participants |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percentage of Participants With Virologic Response Based on HIV-1 RNA Less Than (<)20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Food and Drug Administration (FDA) Snapshot Approach | <20 copies/mL | 89.8 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Response Based on HIV-1 RNA Less Than (<)20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Food and Drug Administration (FDA) Snapshot Approach | <20 copies/mL | 88.4 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Response Based on HIV-1 RNA Less Than (<)20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Food and Drug Administration (FDA) Snapshot Approach | <50 copies/mL | 93.7 Percentage of Participants |
| Control (Baseline to Switch) | Percentage of Participants With Virologic Response Based on HIV-1 RNA Less Than (<)20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Food and Drug Administration (FDA) Snapshot Approach | <200 copies/mL | 94.2 Percentage of Participants |
Secondary
Percent Change From Baseline in 25-hydroxy Vitamin D at Weeks 24 and 48
Percent change from baseline in bone biomarker: 25-hydroxy vitamin D was assessed at Weeks 24 and 48.
Time frame: Baseline, Weeks 24 and 48
Population: The bone investigation substudy (BIS) analysis set included all participants who were randomized and received at least 1 dose of study drug in the study, and had at least one postbaseline value for biomarker data. Here 'n' specifies participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in 25-hydroxy Vitamin D at Weeks 24 and 48 | Percent change at Week 24 | -3.0 Percent change | Standard Error 5.06 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in 25-hydroxy Vitamin D at Weeks 24 and 48 | Percent change at Week 48 | 25.2 Percent change | Standard Error 5.51 |
| Control (Baseline to Switch) | Percent Change From Baseline in 25-hydroxy Vitamin D at Weeks 24 and 48 | Percent change at Week 24 | 4.2 Percent change | Standard Error 6.13 |
| Control (Baseline to Switch) | Percent Change From Baseline in 25-hydroxy Vitamin D at Weeks 24 and 48 | Percent change at Week 48 | 24.9 Percent change | Standard Error 7.46 |
Secondary
Percent Change From Baseline in Parathyroid Hormone (PTH) at Weeks 24 and 48
Percent change from baseline in bone biomarker: PTH was assessed at Weeks 24 and 48.
Time frame: Baseline, Weeks 24 and 48
Population: The bone investigation substudy (BIS) analysis set included all participants who were randomized and received at least 1 dose of study drug in the study, and had at least one postbaseline value for biomarker data. Here 'n' specifies participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in Parathyroid Hormone (PTH) at Weeks 24 and 48 | Percent change at Week 24 | -3.092 Percent change | Standard Error 2.5941 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in Parathyroid Hormone (PTH) at Weeks 24 and 48 | Percent change at Week 48 | -4.510 Percent change | Standard Error 2.5375 |
| Control (Baseline to Switch) | Percent Change From Baseline in Parathyroid Hormone (PTH) at Weeks 24 and 48 | Percent change at Week 24 | 12.034 Percent change | Standard Error 4.1777 |
| Control (Baseline to Switch) | Percent Change From Baseline in Parathyroid Hormone (PTH) at Weeks 24 and 48 | Percent change at Week 48 | 9.436 Percent change | Standard Error 4.4784 |
Secondary
Percent Change From Baseline in Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) Levels at Weeks 24 and 48
Percent change from baseline in bone biomarkers: P1NP and CTX was assessed at Weeks 24 and 48.
Time frame: Baseline, Weeks 24 and 48
Population: The bone investigation substudy (BIS) analysis set included all participants who were randomized and received at least 1 dose of study drug in the study, and had at least one postbaseline value for biomarker data. Here 'n' specifies participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) Levels at Weeks 24 and 48 | P1NP: Percent change at Week 24 | -22.971 Percent Change | Standard Error 1.8818 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) Levels at Weeks 24 and 48 | P1NP: Percent change at Week 48 | -26.752 Percent Change | Standard Error 1.896 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) Levels at Weeks 24 and 48 | CTX: Percent change at Week 24 | -16.772 Percent Change | Standard Error 2.2575 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) Levels at Weeks 24 and 48 | CTX: Percent change at Week 48 | -10.517 Percent Change | Standard Error 3.2325 |
| Control (Baseline to Switch) | Percent Change From Baseline in Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) Levels at Weeks 24 and 48 | CTX: Percent change at Week 48 | 5.433 Percent Change | Standard Error 4.1118 |
| Control (Baseline to Switch) | Percent Change From Baseline in Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) Levels at Weeks 24 and 48 | P1NP: Percent change at Week 24 | -0.027 Percent Change | Standard Error 2.7325 |
| Control (Baseline to Switch) | Percent Change From Baseline in Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) Levels at Weeks 24 and 48 | CTX: Percent change at Week 24 | 16.312 Percent Change | Standard Error 3.8855 |
| Control (Baseline to Switch) | Percent Change From Baseline in Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) Levels at Weeks 24 and 48 | P1NP: Percent change at Week 48 | -3.751 Percent Change | Standard Error 2.6988 |
Secondary
Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48
Percent change from baseline in spine and hip BMD was assessed at Weeks 24 and 48.
Time frame: Baseline, Weeks 24 and 48
Population: The bone investigation substudy (BIS) analysis set included all participants who were randomized and received at least 1 dose of study drug in the study, and had at least one postbaseline value for bone mineral density (BMD) data. Here 'n' specifies participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48 | Spine BMD: Percent change at Week 24 | 1.55 Percent change | Standard Error 0.276 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48 | Spine BMD: Percent change at Week 48 | 2.06 Percent change | Standard Error 0.324 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48 | Hip BMD: Percent change at Week 24 | 0.91 Percent change | Standard Error 0.23 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48 | Hip BMD: Percent change at Week 48 | 1.62 Percent change | Standard Error 0.244 |
| Control (Baseline to Switch) | Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48 | Hip BMD: Percent change at Week 48 | -0.08 Percent change | Standard Error 0.288 |
| Control (Baseline to Switch) | Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48 | Spine BMD: Percent change at Week 24 | 0.18 Percent change | Standard Error 0.342 |
| Control (Baseline to Switch) | Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48 | Hip BMD: Percent change at Week 24 | 0.00 Percent change | Standard Error 0.279 |
| Control (Baseline to Switch) | Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48 | Spine BMD: Percent change at Week 48 | 0.01 Percent change | Standard Error 0.391 |
Comparison: Spine BMD: Percent change at Week 24p-value: <0.00195% CI: [0.697, 2.037]ANCOVA
Comparison: Spine BMD: Percent change at Week 48p-value: <0.00195% CI: [1.277, 2.814]ANCOVA
Comparison: Hip BMD: Percent change at Week 24p-value: =0.00195% CI: [0.366, 1.436]ANCOVA
Comparison: Hip BMD: Percent change at Week 48p-value: <0.00195% CI: [1.144, 2.248]ANCOVA
Secondary
Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Weeks 24 and 48
Percent change from baseline in urine FEPO4 was assessed at Weeks 24 and 48.
Time frame: Baseline, Weeks 24 and 48
Population: ITT analysis set included all the participants who were randomized and received at least 1 dose of study treatment. Here 'n' specifies those participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Weeks 24 and 48 | Percent change at Week 24 | 3.58 Percent change |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Weeks 24 and 48 | Percent change at Week 48 | 8.42 Percent change |
| Control (Baseline to Switch) | Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Weeks 24 and 48 | Percent change at Week 24 | 8.55 Percent change |
| Control (Baseline to Switch) | Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Weeks 24 and 48 | Percent change at Week 48 | 8.57 Percent change |
Comparison: FEPO4 - Change at Week 24p-value: =0.288Van Elteren Test
Comparison: FEPO4 - Change at Week 48p-value: =0.148Van Elteren Test
Secondary
Percent Change From Reference in FEPO4 at Week 96
Percent change from reference in FEPO4 at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Reference in FEPO4 at Week 96 | 4.15 percent change |
| Control (Baseline to Switch) | Percent Change From Reference in FEPO4 at Week 96 | -3.19 percent change |
Secondary
Percent Change From Reference in Hip and Spine BMD at Week 96
The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by DXA 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. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: 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
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of participants analyzed) indicates number of participants evaluable for this outcome measure; and 'n' specifies participants analyzed for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Reference in Hip and Spine BMD at Week 96 | Hip region BMD-T score | 0.0173 percent change | Standard Error 0.00217 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Reference in Hip and Spine BMD at Week 96 | Spine region BMD-T score | 0.0193 percent change | Standard Error 0.00286 |
| Control (Baseline to Switch) | Percent Change From Reference in Hip and Spine BMD at Week 96 | Hip region BMD-T score | 0.0108 percent change | Standard Error 0.00328 |
| Control (Baseline to Switch) | Percent Change From Reference in Hip and Spine BMD at Week 96 | Spine region BMD-T score | 0.0279 percent change | Standard Error 0.00381 |
Secondary
Percent Change From Reference in Levels of 25-OH Vitamin D at Week 96
Percent change from reference in 25-OH Vitamin D at Week 96 were reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: 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
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Reference in Levels of 25-OH Vitamin D at Week 96 | 24.6 percent change | Standard Error 5.16 |
| Control (Baseline to Switch) | Percent Change From Reference in Levels of 25-OH Vitamin D at Week 96 | -1.9 percent change | Standard Error 3.33 |
Secondary
Percent Change From Reference in Levels of PTH at Week 96
Percent change from reference in PTH at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: 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
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Reference in Levels of PTH at Week 96 | -17.171 percent change | Standard Error 2.6774 |
| Control (Baseline to Switch) | Percent Change From Reference in Levels of PTH at Week 96 | -20.466 percent change | Standard Error 3.2559 |
Secondary
Percent Change From Reference in Levels of Serum CTX at Week 96
Percent change from reference in serum CTX at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: 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
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Reference in Levels of Serum CTX at Week 96 | -10.192 percent change | Standard Error 3.0592 |
| Control (Baseline to Switch) | Percent Change From Reference in Levels of Serum CTX at Week 96 | -21.755 percent change | Standard Error 3.4926 |
Secondary
Percent Change From Reference in Levels of Serum P1NP at Week 96
Percent change from reference in serum P1NP levels at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time frame: 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
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Percent Change From Reference in Levels of Serum P1NP at Week 96 | -19.899 percent change | Standard Error 2.2151 |
| Control (Baseline to Switch) | Percent Change From Reference in Levels of Serum P1NP at Week 96 | -18.466 percent change | Standard Error 3.1169 |
Secondary
Predose (Trough) Plasma Concentration (C0h) of Darunavir
Predose (trough) plasma concentration (C0h) of darunavir was determined. Pharmacokinetic (PK) data was only analyzed for participants in the D/C/F/TAF group as per planned analysis.
Time frame: Predose at Weeks 2, 4, 8, 12, 24, 36, and 48
Population: The PK analysis set included all participants randomized to D/C/F/TAF group and received at least 1 dose of study drug in study, and for whom plasma concentration data of any analytes of interest were available. Here 'n' specifies participants who were analyzed for this endpoint at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Predose (Trough) Plasma Concentration (C0h) of Darunavir | Week 2 | 1775.29 Nanogram per milliliter (ng/mL) | Standard Deviation 1698.84 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Predose (Trough) Plasma Concentration (C0h) of Darunavir | Week 4 | 1732.00 Nanogram per milliliter (ng/mL) | Standard Deviation 1389.44 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Predose (Trough) Plasma Concentration (C0h) of Darunavir | Week 8 | 1910.30 Nanogram per milliliter (ng/mL) | Standard Deviation 1501.94 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Predose (Trough) Plasma Concentration (C0h) of Darunavir | Week 12 | 1643.38 Nanogram per milliliter (ng/mL) | Standard Deviation 1328.41 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Predose (Trough) Plasma Concentration (C0h) of Darunavir | Week 24 | 2022.99 Nanogram per milliliter (ng/mL) | Standard Deviation 1965.64 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Predose (Trough) Plasma Concentration (C0h) of Darunavir | Week 36 | 1806.37 Nanogram per milliliter (ng/mL) | Standard Deviation 1669.43 |
| D/C/F/TAF (Test) (Baseline [BL] to End of Extension [EOE]) | Predose (Trough) Plasma Concentration (C0h) of Darunavir | Week 48 | 1899.79 Nanogram per milliliter (ng/mL) | Standard Deviation 1833.09 |