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D/C/F/TAF Versus COBI-boosted DRV Plus FTC/TDF in HIV-1 Infected, Antiretroviral Treatment Naive Adults

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ClinicalTrials.gov Identifier: NCT01565850
Recruitment Status : Completed
First Posted : March 29, 2012
Results First Posted : April 11, 2016
Last Update Posted : April 11, 2016
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Acquired Immunodeficiency Syndrome
HIV Infections
Interventions Drug: D/C/F/TAF
Drug: DRV
Drug: COBI
Drug: FTC/TDF
Drug: D/C/F/TAF Placebo
Drug: DRV Placebo
Drug: COBI Placebo
Drug: FTC/TDF Placebo
Enrollment 153

Recruitment Details Participants were enrolled at study sites in the United States (including Puerto Rico). The first participant was screened on 16 April 2012. The last study visit occurred on 19 February 2014.
Pre-assignment Details 232 participants were screened.
Arm/Group Title D/C/F/TAF DRV+COBI+FTC/TDF
Hide Arm/Group Description Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) (800/150/200/10 mg) fixed-dose combination (FDC) tablet plus darunavir (DRV) placebo plus cobicistat (COBI) placebo plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo once daily DRV 800 mg tablet plus COBI 150 mg tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo once daily
Period Title: Overall Study
Started 103 50
Completed 83 42
Not Completed 20 8
Reason Not Completed
Adverse Event             0             1
Lost to Follow-up             12             4
Investigator’s Discretion             2             1
Participant noncompliance             2             0
Withdrew Consent             4             2
Arm/Group Title D/C/F/TAF DRV+COBI+FTC/TDF Total
Hide Arm/Group Description D/C/F/TAF (800/150/200/10 mg) FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo once daily DRV 800 mg tablet plus COBI 150 mg tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo once daily Total of all reporting groups
Overall Number of Baseline Participants 103 50 153
Hide Baseline Analysis Population Description
Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 103 participants 50 participants 153 participants
35  (11.3) 37  (10.9) 35  (11.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants 50 participants 153 participants
Female
8
   7.8%
3
   6.0%
11
   7.2%
Male
95
  92.2%
47
  94.0%
142
  92.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants 50 participants 153 participants
Hispanic or Latino
23
  22.3%
9
  18.0%
32
  20.9%
Not Hispanic or Latino
80
  77.7%
41
  82.0%
121
  79.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 103 participants 50 participants 153 participants
White 62 30 92
Black or African American 36 17 53
Asian 2 1 3
Native Hawaiian or Other Pacific Islander 1 1 2
Other 2 1 3
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 103 participants 50 participants 153 participants
103 50 153
HIV-1 RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 copies/mL
Number Analyzed 103 participants 50 participants 153 participants
4.70  (0.516) 4.65  (0.514) 4.68  (0.515)
HIV-1 RNA Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 103 participants 50 participants 153 participants
≤ 100,000 copies/mL 80 43 123
> 100,000 to ≤ 400,000 copies/mL 17 5 22
> 400,000 copies/mL 6 2 8
CD4 Cell Count  
Mean (Standard Deviation)
Unit of measure:  cells/µL
Number Analyzed 103 participants 50 participants 153 participants
395  (169.3) 464  (261.6) 417  (205.7)
CD4 Cell Count Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 103 participants 50 participants 153 participants
< 50 cells/μL 1 1 2
50 to ≤ 199 cells/µL 10 9 19
200 to ≤ 349 cells/µL 37 8 45
351 to ≤ 499 cells/µL 27 12 39
≥ 500 cells/μL 28 20 48
1.Primary Outcome
Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24
Hide Description The snapshot algorithm was used which defines a patient'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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: participant who were randomized;enrolled and received at least one dose of study drug
Arm/Group Title D/C/F/TAF DRV+COBI+FTC/TDF
Hide Arm/Group Description:
D/C/F/TAF (800/150/200/10 mg) FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo once daily
DRV 800 mg tablet plus COBI 150 mg tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo once daily
Overall Number of Participants Analyzed 103 50
Measure Type: Number
Unit of Measure: percentage of participants
74.8 74.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF, DRV+COBI+FTC/TDF
Comments The null hypothesis was that the D/C/F/TAF group is at least 12% worse than the DRV+COBI+FTC/TDF group with respect to the percentage of participants achieving HIV-1 RNA < 50 copies/mL (response rate as defined by the snapshot analysis algorithm) at Week 24; the alternative hypothesis was that the response rate in the D/C/F/TAF group is less than 12% worse than that in the DRV+COBI +FTC/TDF group.
Type of Statistical Test Non-Inferiority or Equivalence
Comments A total sample size of 150 HIV-1 infected participants, randomized in a 2:1 ratio to 2 groups, would achieve 56% power to evaluate noninferiority with respect to the response rate of HIV-1 RNA < 50 copies/mL at Week 24 if a response rate of 0.88 for both arms, a noninferiority margin of 0.12, and the significance level of the test at a one-sided 0.025 level were assumed.
Statistical Test of Hypothesis P-Value 0.64
Comments The p-value for the superiority test comparing the percentages of virologic success was from the Cochran-Mantel-Haenszel test stratified by baseline HIV-1 RNA and race strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 3.3
Confidence Interval (2-Sided) 95%
-11.4 to 18.1
Estimation Comments The difference in percentages of virologic success and its 95% confidence interval (CI) were calculated based on baseline HIV-1 RNA and race stratum-adjusted Mantel-Haenszel proportion.
2.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
Hide Description The snapshot algorithm was used which defines a patient'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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title D/C/F/TAF DRV+COBI+FTC/TDF
Hide Arm/Group Description:
D/C/F/TAF (800/150/200/10 mg) FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo once daily
DRV 800 mg tablet plus COBI 150 mg tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo once daily
Overall Number of Participants Analyzed 103 50
Measure Type: Number
Unit of Measure: percentage of participants
76.7 84.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF, DRV+COBI+FTC/TDF
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The null hypothesis was that the D/C/F/TAF group is at least 12% worse than the DRV+COBI+FTC/TDF group with respect to the percentage of participants achieving HIV-1 RNA < 50 copies/mL (response rate as defined by the snapshot analysis algorithm) at Week 48; the alternative hypothesis was that the response rate in the D/C/F/TAF group is less than 12% worse than that in the DRV+COBI +FTC/TDF group.
Statistical Test of Hypothesis P-Value 0.35
Comments The p-value for the superiority test comparing the percentages of virologic success was from the Cochran-Mantel-Haenszel test stratified by baseline HIV-1 RNA and race strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value -6.2
Confidence Interval (2-Sided) 95%
-19.9 to 7.4
Estimation Comments The difference in percentages of virologic success and its 95% CI were calculated based on baseline HIV-1 RNA and race stratum-adjusted Mantel-Haenszel proportion.
3.Secondary Outcome
Title Change From Baseline in HIV-1 RNA at Week 24
Hide Description [Not Specified]
Time Frame Baseline; Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with Week 24 data were analyzed.
Arm/Group Title D/C/F/TAF DRV+COBI+FTC/TDF
Hide Arm/Group Description:
D/C/F/TAF (800/150/200/10 mg) FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo once daily
DRV 800 mg tablet plus COBI 150 mg tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo once daily
Overall Number of Participants Analyzed 92 48
Mean (Standard Deviation)
Unit of Measure: log10 copies/mL
-3.20  (0.653) -3.18  (0.416)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF, DRV+COBI+FTC/TDF
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.67
Comments The p-value, difference in least squares mean (LSM), and its 95% CI were from ANOVA model with baseline HIV-1 RNA level (≤ 100,000 or > 100,000 copies/mL) and race (Black or non-Black) as fixed effects in the model.
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.14 to 0.21
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in HIV-1 RNA at Week 48
Hide Description [Not Specified]
Time Frame Baseline; Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with Week 48 data were analyzed.
Arm/Group Title D/C/F/TAF DRV+COBI+FTC/TDF
Hide Arm/Group Description:
D/C/F/TAF (800/150/200/10 mg) FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo once daily
DRV 800 mg tablet plus COBI 150 mg tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo once daily
Overall Number of Participants Analyzed 89 47
Mean (Standard Deviation)
Unit of Measure: log10 copies/mL
-3.27  (0.668) -3.26  (0.521)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF, DRV+COBI+FTC/TDF
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments The p-value, difference in LSM, and its 95% CI were from ANOVA model with baseline HIV-1 RNA level (≤ 100,000 or > 100,000 copies/mL) and race (Black or non-Black) as fixed effects in the model.
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.11 to 0.23
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in CD4+ Cell Count at Week 24
Hide Description [Not Specified]
Time Frame Baseline; Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with Week 24 data were analyzed.
Arm/Group Title D/C/F/TAF DRV+COBI+FTC/TDF
Hide Arm/Group Description:
D/C/F/TAF (800/150/200/10 mg) FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo once daily
DRV 800 mg tablet plus COBI 150 mg tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo once daily
Overall Number of Participants Analyzed 91 48
Mean (Standard Deviation)
Unit of Measure: cells/µL
186  (137.9) 139  (185.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF, DRV+COBI+FTC/TDF
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments The p-value, difference in LSM, and its 95% CI were from ANOVA model with baseline HIV-1 RNA level (≤ 100,000 or > 100,000 copies/mL) and race (Black or non-Black) as fixed effects in the model.
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 45
Confidence Interval (2-Sided) 95%
-10 to 101
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in CD4+ Cell Count at Week 48
Hide Description [Not Specified]
Time Frame Baseline; Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with Week 48 data were analyzed.
Arm/Group Title D/C/F/TAF DRV+COBI+FTC/TDF
Hide Arm/Group Description:
D/C/F/TAF (800/150/200/10 mg) FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo once daily
DRV 800 mg tablet plus COBI 150 mg tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo once daily
Overall Number of Participants Analyzed 85 46
Mean (Standard Deviation)
Unit of Measure: cells/µL
231  (141.9) 212  (151.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF, DRV+COBI+FTC/TDF
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments The p-value, difference in LSM, and its 95% CI were from ANOVA model with baseline HIV-1 RNA level (≤ 100,000 or > 100,000 copies/mL) and race (Black or non-Black) as fixed effects in the model.
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 18
Confidence Interval (2-Sided) 95%
-35 to 72
Estimation Comments [Not Specified]
Time Frame Baseline through end of study drug treatment (average exposure: D/C/F/TAF group = 61.7 weeks; DRV+COBI+FTC/TDF group = 66.1 weeks) plus 30 days
Adverse Event Reporting Description Safety Analysis Set: participants who were randomized and received at least one dose of study drug
 
Arm/Group Title D/C/F/TAF DRV+COBI+FTC/TDF
Hide Arm/Group Description D/C/F/TAF (800/150/200/10 mg) FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo once daily DRV 800 mg tablet plus COBI 150 mg tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo once daily
All-Cause Mortality
D/C/F/TAF DRV+COBI+FTC/TDF
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
D/C/F/TAF DRV+COBI+FTC/TDF
Affected / at Risk (%) Affected / at Risk (%)
Total   5/103 (4.85%)   2/50 (4.00%) 
Gastrointestinal disorders     
Diarrhoea haemorrhagic  1  1/103 (0.97%)  0/50 (0.00%) 
Immune system disorders     
Hypersensitivity  1  1/103 (0.97%)  0/50 (0.00%) 
Infections and infestations     
Bronchitis  1  0/103 (0.00%)  1/50 (2.00%) 
Bronchitis viral  1  0/103 (0.00%)  1/50 (2.00%) 
Cellulitis  1  1/103 (0.97%)  0/50 (0.00%) 
Pneumonia  1  0/103 (0.00%)  1/50 (2.00%) 
Psychiatric disorders     
Psychotic disorder  1  1/103 (0.97%)  0/50 (0.00%) 
Substance abuse  1  1/103 (0.97%)  0/50 (0.00%) 
Renal and urinary disorders     
Renal tubular disorder  1  0/103 (0.00%)  1/50 (2.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
D/C/F/TAF DRV+COBI+FTC/TDF
Affected / at Risk (%) Affected / at Risk (%)
Total   77/103 (74.76%)   40/50 (80.00%) 
Gastrointestinal disorders     
Abdominal pain  1  6/103 (5.83%)  3/50 (6.00%) 
Diarrhoea  1  22/103 (21.36%)  13/50 (26.00%) 
Flatulence  1  5/103 (4.85%)  6/50 (12.00%) 
Haemorrhoids  1  3/103 (2.91%)  4/50 (8.00%) 
Nausea  1  13/103 (12.62%)  5/50 (10.00%) 
Vomiting  1  4/103 (3.88%)  5/50 (10.00%) 
General disorders     
Fatigue  1  14/103 (13.59%)  9/50 (18.00%) 
Pyrexia  1  7/103 (6.80%)  2/50 (4.00%) 
Infections and infestations     
Bronchitis  1  9/103 (8.74%)  2/50 (4.00%) 
Folliculitis  1  3/103 (2.91%)  4/50 (8.00%) 
Influenza  1  2/103 (1.94%)  3/50 (6.00%) 
Nasopharyngitis  1  5/103 (4.85%)  3/50 (6.00%) 
Pharyngitis  1  1/103 (0.97%)  3/50 (6.00%) 
Sinusitis  1  7/103 (6.80%)  4/50 (8.00%) 
Tooth abscess  1  0/103 (0.00%)  3/50 (6.00%) 
Upper respiratory tract infection  1  16/103 (15.53%)  7/50 (14.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  4/103 (3.88%)  3/50 (6.00%) 
Vitamin D deficiency  1  2/103 (1.94%)  5/50 (10.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  9/103 (8.74%)  0/50 (0.00%) 
Back pain  1  1/103 (0.97%)  3/50 (6.00%) 
Pain in extremity  1  8/103 (7.77%)  5/50 (10.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Anogenital warts  1  3/103 (2.91%)  3/50 (6.00%) 
Nervous system disorders     
Headache  1  7/103 (6.80%)  4/50 (8.00%) 
Psychiatric disorders     
Insomnia  1  6/103 (5.83%)  2/50 (4.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  7/103 (6.80%)  3/50 (6.00%) 
Oropharyngeal pain  1  5/103 (4.85%)  4/50 (8.00%) 
Sinus congestion  1  6/103 (5.83%)  3/50 (6.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  12/103 (11.65%)  4/50 (8.00%) 
Vascular disorders     
Hypertension  1  2/103 (1.94%)  3/50 (6.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
There were no limitations affecting the analysis or results.
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
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01565850     History of Changes
Other Study ID Numbers: GS-US-299-0102
First Submitted: March 27, 2012
First Posted: March 29, 2012
Results First Submitted: March 11, 2016
Results First Posted: April 11, 2016
Last Update Posted: April 11, 2016