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Switching From a Tenofovir Disoproxil Fumarate (TDF) Containing Regimen to Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Infected Adults Aged ≥ 60 Years

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ClinicalTrials.gov Identifier: NCT02616783
Recruitment Status : Completed
First Posted : November 30, 2015
Results First Posted : February 19, 2019
Last Update Posted : March 4, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV-1 Infection
Interventions Drug: E/C/F/TAF
Drug: TDF
Drug: FTC
Drug: FTC/TDF
Drug: 3TC
Drug: Third agent
Enrollment 167
Recruitment Details Participants were enrolled at study sites in Europe. The first participant was screened on 22 December 2015. The last study visit occurred on 21 March 2018.
Pre-assignment Details 214 participants were screened.
Arm/Group Title E/C/F/TAF Stay on Baseline Regimen
Hide Arm/Group Description Participants switched from tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or 3TC plus a third agent to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) fixed-dose combination (FDC) tablet once daily for 48 weeks. Participants stayed on current regimen of TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent for 48 weeks.
Period Title: Overall Study
Started 111 56
Completed 105 54
Not Completed 6 2
Reason Not Completed
Randomized but Not Treated             1             0
Adverse Event             1             0
Death             1             0
Non-Compliance with Study Drug             1             0
Protocol Violation             1             1
Withdrew Consent             1             1
Arm/Group Title E/C/F/TAF Stay on Baseline Regimen Total
Hide Arm/Group Description Participants switched from TDF and FTC or 3TC plus a third agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily for 48 weeks. Participants stayed on current regimen of TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent for 48 weeks. Total of all reporting groups
Overall Number of Baseline Participants 110 56 166
Hide Baseline Analysis Population Description
Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 110 participants 56 participants 166 participants
65  (4.6) 66  (4.9) 66  (4.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 110 participants 56 participants 166 participants
Female
14
  12.7%
5
   8.9%
19
  11.4%
Male
96
  87.3%
51
  91.1%
147
  88.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 110 participants 56 participants 166 participants
Hispanic or Latino
16
  14.5%
8
  14.3%
24
  14.5%
Not Hispanic or Latino
88
  80.0%
42
  75.0%
130
  78.3%
Unknown or Not Reported
6
   5.5%
6
  10.7%
12
   7.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 110 participants 56 participants 166 participants
American Indian or Alaska Native
0
   0.0%
1
   1.8%
1
   0.6%
Black or African American
2
   1.8%
2
   3.6%
4
   2.4%
White
103
  93.6%
49
  87.5%
152
  91.6%
Not Permitted
5
   4.5%
4
   7.1%
9
   5.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Belgium Number Analyzed 110 participants 56 participants 166 participants
8
   7.3%
1
   1.8%
9
   5.4%
Italy Number Analyzed 110 participants 56 participants 166 participants
36
  32.7%
15
  26.8%
51
  30.7%
United Kingdom Number Analyzed 110 participants 56 participants 166 participants
8
   7.3%
3
   5.4%
11
   6.6%
France Number Analyzed 110 participants 56 participants 166 participants
29
  26.4%
23
  41.1%
52
  31.3%
Spain Number Analyzed 110 participants 56 participants 166 participants
29
  26.4%
14
  25.0%
43
  25.9%
HIV-1 RNA Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 110 participants 56 participants 166 participants
< 50 copies/mL
109
  99.1%
56
 100.0%
165
  99.4%
≥ 50 copies/mL
1
   0.9%
0
   0.0%
1
   0.6%
CD4+ Cell Count  
Mean (Standard Deviation)
Unit of measure:  cells/µL
Number Analyzed 110 participants 56 participants 166 participants
649  (255.6) 676  (316.5) 658  (277.0)
CD4+ Cell Count Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 110 participants 56 participants 166 participants
≥ 50 to < 200 cells/µL
0
   0.0%
2
   3.6%
2
   1.2%
≥ 200 to < 350 cells/µL
12
  10.9%
8
  14.3%
20
  12.0%
≥ 350 to < 500 cells/µL
18
  16.4%
7
  12.5%
25
  15.1%
≥ 500 cells/µL
80
  72.7%
39
  69.6%
119
  71.7%
Spine Bone Mineral Density (BMD)   [1] 
Mean (Standard Deviation)
Unit of measure:  G/cm^2
Number Analyzed 109 participants 55 participants 164 participants
1.036  (0.1886) 1.052  (0.1789) 1.042  (0.1850)
[1]
Measure Analysis Population Description: The Spine Dual-Energy X-ray Absorptiometry (DXA) Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, had non missing screening spine BMD values, and did not have any major protocol violations.
Hip BMD   [1] 
Mean (Standard Deviation)
Unit of measure:  G/cm^2
Number Analyzed 109 participants 55 participants 164 participants
0.922  (0.1332) 0.927  (0.1346) 0.924  (0.1332)
[1]
Measure Analysis Population Description: The Hip DXA Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, had non missing screening hip BMD values, and did not have any major protocol violations.
1.Primary Outcome
Title Percent Change From Baseline to Week 48 in Spine BMD
Hide Description [Not Specified]
Time Frame Baseline; Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Spine DXA Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TAF Stay on Baseline Regimen
Hide Arm/Group Description:
Participants switched from TDF and FTC or 3TC plus a third agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily for 48 weeks.
Participants stayed on current regimen of TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent for 48 weeks.
Overall Number of Participants Analyzed 102 54
Mean (Standard Deviation)
Unit of Measure: Percent change
2.237  (3.2727) -0.104  (3.3854)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Regimen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments P-value was calculated using the ANOVA model with baseline spine BMD score, sex, and treatment as fixed effects.
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 2.427
Confidence Interval (2-Sided) 95%
1.337 to 3.517
Estimation Comments The 95% confidence intervals (CI) were calculated using the ANOVA model with baseline spine BMD score, sex, and treatment as fixed effects.
2.Primary Outcome
Title Percent Change From Baseline to Week 48 in Hip BMD
Hide Description [Not Specified]
Time Frame Baseline; Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Hip DXA Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TAF Stay on Baseline Regimen
Hide Arm/Group Description:
Participants switched from TDF and FTC or 3TC plus a third agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily for 48 weeks.
Participants stayed on current regimen of TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent for 48 weeks.
Overall Number of Participants Analyzed 101 54
Mean (Standard Deviation)
Unit of Measure: Percent change
1.330  (2.1968) -0.726  (3.2069)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Regimen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments P-value was calculated using the ANOVA model with baseline hip BMD score, sex, and treatment as fixed effects.
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 2.036
Confidence Interval (2-Sided) 95%
1.168 to 2.904
Estimation Comments The 95% CIs were calculated using the ANOVA model with baseline hip BMD score, sex, and treatment as fixed effects.
3.Secondary Outcome
Title Percent Change From Baseline to Week 24 in Spine BMD
Hide Description [Not Specified]
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Spine DXA Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TAF Stay on Baseline Regimen
Hide Arm/Group Description:
Participants switched from TDF and FTC or 3TC plus a third agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily for 48 weeks.
Participants stayed on current regimen of TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent for 48 weeks.
Overall Number of Participants Analyzed 104 54
Mean (Standard Deviation)
Unit of Measure: Percent change
1.625  (3.2346) -0.027  (2.9875)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Regimen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments P-value was calculated using the ANOVA model with baseline spine BMD score, sex, and treatment as fixed effects.
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 1.749
Confidence Interval (2-Sided) 95%
0.726 to 2.771
Estimation Comments The 95% CIs were calculated using the ANOVA model with baseline spine BMD score, sex, and treatment as fixed effects.
4.Secondary Outcome
Title Percent Change From Baseline to Week 24 in Hip BMD
Hide Description [Not Specified]
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Hip DXA Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TAF Stay on Baseline Regimen
Hide Arm/Group Description:
Participants switched from TDF and FTC or 3TC plus a third agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily for 48 weeks.
Participants stayed on current regimen of TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent for 48 weeks.
Overall Number of Participants Analyzed 103 54
Mean (Standard Deviation)
Unit of Measure: Percent change
0.808  (1.9084) -0.537  (2.7647)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Regimen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments P-value was calculated using the ANOVA model with baseline hip BMD score, sex, and treatment as fixed effects.
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 1.351
Confidence Interval (2-Sided) 95%
0.602 to 2.099
Estimation Comments The 95% CIs were calculated using the ANOVA model with baseline hip BMD score, sex, and treatment as fixed effects.
5.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm
Hide Description The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, and did not have any major protocol violations.
Arm/Group Title E/C/F/TAF Stay on Baseline Regimen
Hide Arm/Group Description:
Participants switched from TDF and FTC or 3TC plus a third agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily for 48 weeks.
Participants stayed on current regimen of TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent for 48 weeks.
Overall Number of Participants Analyzed 109 55
Measure Type: Number
Unit of Measure: Percentage of participants
94.5 100.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Regimen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments P-values for the superiority test comparing the percentages of participants with HIV-1 RNA < 50 copies/mL were from the Fisher exact test.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value -5.5
Confidence Interval (2-Sided) 95%
-11.8 to 1.6
Estimation Comments Differences in percentages and 95% CI were generated based on exact method.
6.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
Hide Description The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, and did not have any major protocol violations.
Arm/Group Title E/C/F/TAF Stay on Baseline Regimen
Hide Arm/Group Description:
Participants switched from TDF and FTC or 3TC plus a third agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily for 48 weeks.
Participants stayed on current regimen of TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent for 48 weeks.
Overall Number of Participants Analyzed 109 55
Measure Type: Number
Unit of Measure: Percentage of participants
93.6 94.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Regimen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments P-values for the superiority test comparing the percentages of participants with HIV-1 RNA < 50 copies/mL were from the Fisher exact test.
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-8.5 to 9.3
Estimation Comments Differences in percentages and 95% CI were generated based on exact method.
7.Secondary Outcome
Title Change From Baseline in CD4+ Cell Count at Week 24
Hide Description [Not Specified]
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TAF Stay on Baseline Regimen
Hide Arm/Group Description:
Participants switched from TDF and FTC or 3TC plus a third agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily for 48 weeks.
Participants stayed on current regimen of TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent for 48 weeks.
Overall Number of Participants Analyzed 99 54
Mean (Standard Deviation)
Unit of Measure: cells/μL
48  (161.9) -4  (153.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Regimen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.053
Comments [Not Specified]
Method ANOVA
Comments The p-value, difference in least square means (LSM), and its 95% CI were from ANOVA model with treatment as a fixed effect.
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 52
Confidence Interval (2-Sided) 95%
-1 to 106
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change in Baseline in CD4+ Cell Count at Week 48
Hide Description [Not Specified]
Time Frame Baseline; Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TAF Stay on Baseline Regimen
Hide Arm/Group Description:
Participants switched from TDF and FTC or 3TC plus a third agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily for 48 weeks.
Participants stayed on current regimen of TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent for 48 weeks.
Overall Number of Participants Analyzed 102 50
Mean (Standard Deviation)
Unit of Measure: cells/μL
56  (177.7) -1  (149.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Regimen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.051
Comments [Not Specified]
Method ANOVA
Comments The p-value, difference in LSM, and its 95% CI were from ANOVA model with treatment as a fixed effect.
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 57
Confidence Interval (2-Sided) 95%
0 to 115
Estimation Comments [Not Specified]
Time Frame Up to 48 weeks plus 30 days
Adverse Event Reporting Description Safety Analysis Set included participants who were randomized into the study and received at least 1 dose of study drug.
 
Arm/Group Title E/C/F/TAF Stay on Baseline Regimen
Hide Arm/Group Description Participants switched from TDF and FTC or 3TC plus a third agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily for 48 weeks. Participants stayed on current regimen of TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent for 48 weeks.
All-Cause Mortality
E/C/F/TAF Stay on Baseline Regimen
Affected / at Risk (%) Affected / at Risk (%)
Total   1/110 (0.91%)   0/56 (0.00%) 
Hide Serious Adverse Events
E/C/F/TAF Stay on Baseline Regimen
Affected / at Risk (%) Affected / at Risk (%)
Total   10/110 (9.09%)   1/56 (1.79%) 
Cardiac disorders     
Acute coronary syndrome † 1  1/110 (0.91%)  1/56 (1.79%) 
Cardiac arrest † 1  1/110 (0.91%)  0/56 (0.00%) 
Hepatobiliary disorders     
Cholecystitis acute † 1  1/110 (0.91%)  0/56 (0.00%) 
Infections and infestations     
Escherichia sepsis † 1  1/110 (0.91%)  0/56 (0.00%) 
Pneumonia † 1  1/110 (0.91%)  0/56 (0.00%) 
Sepsis † 1  1/110 (0.91%)  0/56 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  1/110 (0.91%)  0/56 (0.00%) 
Joint swelling † 1  1/110 (0.91%)  0/56 (0.00%) 
Osteonecrosis † 1  1/110 (0.91%)  0/56 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colorectal cancer † 1  1/110 (0.91%)  0/56 (0.00%) 
Hepatocellular carcinoma † 1  1/110 (0.91%)  0/56 (0.00%) 
Nervous system disorders     
Loss of consciousness † 1  1/110 (0.91%)  0/56 (0.00%) 
Neuritis cranial † 1  1/110 (0.91%)  0/56 (0.00%) 
Syncope † 1  1/110 (0.91%)  0/56 (0.00%) 
Renal and urinary disorders     
Acute kidney injury † 1  1/110 (0.91%)  0/56 (0.00%) 
Renal colic † 1  1/110 (0.91%)  0/56 (0.00%) 
Reproductive system and breast disorders     
Prostatomegaly † 1  1/110 (0.91%)  0/56 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
E/C/F/TAF Stay on Baseline Regimen
Affected / at Risk (%) Affected / at Risk (%)
Total   47/110 (42.73%)   20/56 (35.71%) 
Gastrointestinal disorders     
Diarrhoea † 1  8/110 (7.27%)  2/56 (3.57%) 
Infections and infestations     
Bronchitis † 1  4/110 (3.64%)  6/56 (10.71%) 
Nasopharyngitis † 1  12/110 (10.91%)  3/56 (5.36%) 
Urinary tract infection † 1  4/110 (3.64%)  3/56 (5.36%) 
Metabolism and nutrition disorders     
Vitamin D deficiency † 1  7/110 (6.36%)  4/56 (7.14%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  6/110 (5.45%)  4/56 (7.14%) 
Back pain † 1  9/110 (8.18%)  2/56 (3.57%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  6/110 (5.45%)  0/56 (0.00%) 
Vascular disorders     
Hypertension † 1  7/110 (6.36%)  1/56 (1.79%) 
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gilead Clinical Study Information Center
Organization: Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
EMail: GileadClinicalTrials@gilead.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02616783    
Other Study ID Numbers: GS-US-292-1826
2015-002712-32 ( EudraCT Number )
First Submitted: November 23, 2015
First Posted: November 30, 2015
Results First Submitted: January 31, 2019
Results First Posted: February 19, 2019
Last Update Posted: March 4, 2020