Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of E/C/F/TDF (Stribild®) Versus RTV-Boosted ATV Plus FTC/TDF (Truvada®) in HIV-1 Infected, Antiretroviral Treatment-Naive Women (WAVES)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01705574
Recruitment Status : Completed
First Posted : October 12, 2012
Results First Posted : March 10, 2016
Last Update Posted : October 30, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Acquired Immunodeficiency Syndrome
HIV Infections
Interventions Drug: E/C/F/TDF
Drug: RTV
Drug: ATV
Drug: FTC/TDF
Drug: E/C/F/TDF Placebo
Drug: RTV Placebo
Drug: ATV Placebo
Drug: FTC/TDF Placebo
Drug: E/C/F/TAF
Enrollment 583
Recruitment Details Participants were enrolled at study sites in North America, Europe, Dominican Republic, Thailand, and Uganda. The first participant was screened on 24 October 2012. The last Week 48 study visit occurred on 11 February 2015.
Pre-assignment Details 810 participants were screened.
Arm/Group Title E/C/F/TDF ATV+RTV+FTC/TDF
Hide Arm/Group Description Double-Blind Phase: Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild®; E/C/F/TDF) (150/150/200/300 mg) fixed-dose combination (FDC) + atazanavir (ATV) placebo + ritonavir (RTV) placebo + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo once daily for 48 weeks Double-Blind Phase: ATV 300 mg boosted with RTV 100 mg + FTC/TDF (Truvada®; 200/300 mg) FDC + E/C/F/TDF placebo once daily for 48 weeks
Period Title: Overall Study
Started 293 290
Completed 126 127
Not Completed 167 163
Reason Not Completed
Randomized but Not Treated             4             4
Adverse Event             3             9
Pregnancy             1             1
Non-Compliance with Study Drug             4             4
Protocol Violation             1             0
Withdrew Consent             8             5
Lost to Follow-up             11             15
Still on Study             135             125
Arm/Group Title E/C/F/TDF ATV+RTV+FTC/TDF Total
Hide Arm/Group Description Double-Blind Phase: E/C/F/TDF (150/150/200/300 mg) FDC + ATV placebo + RTV placebo + FTC/TDF placebo once daily for 48 weeks Double-Blind Phase: ATV 300 mg boosted with RTV 100 mg + FTC/TDF (200/300 mg) FDC + E/C/F/TDF placebo once daily for 48 weeks Total of all reporting groups
Overall Number of Baseline Participants 289 286 575
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 289 participants 286 participants 575 participants
36  (10.1) 36  (9.7) 36  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 289 participants 286 participants 575 participants
Female
289
 100.0%
286
 100.0%
575
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 289 participants 286 participants 575 participants
Asian 9 17 26
Black 143 133 276
Native Hawaiian or Pacific Islander 0 1 1
White 128 119 247
Other 9 15 24
Not Permitted 0 1 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 289 participants 286 participants 575 participants
Hispanic or Latino 20 24 44
Not Hispanic or Latino 269 262 531
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 289 participants 286 participants 575 participants
Russian Federation 101 91 192
United States 59 60 119
United Kingdom 8 12 20
Thailand 9 15 24
Portugal 8 13 21
Belgium 3 5 8
Dominican Republic 6 13 19
Italy 4 1 5
Mexico 3 1 4
Uganda 87 74 161
France 1 1 2
HIV-1 RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 copies/mL
Number Analyzed 289 participants 286 participants 575 participants
4.51  (0.724) 4.52  (0.781) 4.51  (0.753)
HIV-1 RNA Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 289 participants 286 participants 575 participants
≤ 100,000 220 214 434
> 100,000 to ≤400,000 44 50 94
> 400,000 25 22 47
CD4 Cell Count  
Mean (Standard Deviation)
Unit of measure:  cells/µL
Number Analyzed 289 participants 286 participants 575 participants
376  (199.6) 385  (210.2) 381  (204.8)
1.Primary Outcome
Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 of the Double-Blind Phase
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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) Analysis Set: participants who were randomized and received at least one dose of study drug.
Arm/Group Title E/C/F/TDF ATV+RTV+FTC/TDF
Hide Arm/Group Description:
Double-Blind Phase: E/C/F/TDF (150/150/200/300 mg) FDC + ATV placebo + RTV placebo + FTC/TDF placebo once daily for 48 weeks
Double-Blind Phase: ATV 300 mg boosted with RTV 100 mg + FTC/TDF (200/300 mg) FDC + E/C/F/TDF placebo once daily for 48 weeks
Overall Number of Participants Analyzed 289 286
Measure Type: Number
Unit of Measure: percentage of participants
87.2 80.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection E/C/F/TDF, ATV+RTV+FTC/TDF
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The null hypothesis was that the E/C/F/TDF group was at least 12% worse than the ATV+RTV+FTC/TDF group with respect to the percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 (response rate as defined by the snapshot analysis algorithm). The alternative hypothesis was that the E/C/F/TDF group was less than 12% worse than the ATV+RTV+FTC/TDF group.
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 6.5
Confidence Interval (2-Sided) 95.2%
0.4 to 12.6
Estimation Comments Difference in percentages of virologic success and its 95.2% confidence interval (CI) were calculated based on baseline HIV-1 RNA and race stratum-adjusted Mantel-Haenszel (MH) proportion.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection E/C/F/TDF, ATV+RTV+FTC/TDF
Comments If noninferiority of E/C/F/TDF versus ATV+RTV+FTC/TDF was established, the same 95.2% CI used in evaluating noninferiority was used to evaluate superiority. The baseline HIV-1 RNA and race stratum-stratified, 2-sided CMH test was also used to assess superiority as a secondary assessment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.034
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments P-value comparing virologic success was from the CMH test stratified by baseline HIV-1 RNA and race strata.
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 6.5
Confidence Interval (2-Sided) 95.2%
0.4 to 12.6
Estimation Comments Difference in percentages of virologic success and its 95.2% CI were calculated based on baseline HIV-1 RNA and race stratum-adjusted MH proportion. If the lower bound of the CI was > 0, superiority of E/C/F/TDF over ATV+RTV+FTC/TDF was established.
2.Secondary Outcome
Title Change From Baseline in CD4+ Cell Count at Week 48 of the Double-Blind Phase
Hide Description [Not Specified]
Time Frame Baseline; Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TDF ATV+RTV+FTC/TDF
Hide Arm/Group Description:
Double-Blind Phase: E/C/F/TDF (150/150/200/300 mg) FDC + ATV placebo + RTV placebo + FTC/TDF placebo once daily for 48 weeks
Double-Blind Phase: ATV 300 mg boosted with RTV 100 mg + FTC/TDF (200/300 mg) FDC + E/C/F/TDF placebo once daily for 48 weeks
Overall Number of Participants Analyzed 263 243
Mean (Standard Deviation)
Unit of Measure: cells/μL
221  (165.1) 212  (176.8)
3.Secondary Outcome
Title Percentage of Participants Receiving Open-Label E/C/F/TDF With HIV-1 RNA < 50 Copies/mL at Week 48 of the Open- Label Extension Phase
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 Open-Label Extension Week 48
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Percentage of Participants Receiving E/C/F/TDF or ATV+RTV+FTC/TDF With HIV-1 RNA < 50 Copies/mL at Week 48 of the Open-Label Extension Phase
Hide Description [Not Specified]
Time Frame Open-Label Extension Week 48
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Change in CD4+ Cell Count at Week 48 of the Open-Label Extension Phase
Hide Description [Not Specified]
Time Frame Baseline; Open-Label Extension Week 48
Outcome Measure Data Not Reported
Time Frame Baseline through Week 48 Data Cut (average: E/C/F/TDF = 55.9 weeks; ATV+RTV+FTC/TDF = 52.8 weeks)
Adverse Event Reporting Description Safety Analysis Set: participants who were randomized and received at least one dose of study drug.
 
Arm/Group Title E/C/F/TDF ATV+RTV+FTC/TDF
Hide Arm/Group Description Double-Blind Phase: E/C/F/TDF (150/150/200/300 mg) FDC + ATV placebo + RTV placebo + FTC/TDF placebo once daily for 48 weeks Double-Blind Phase: ATV 300 mg boosted with RTV 100 mg + FTC/TDF (200/300 mg) FDC + E/C/F/TDF placebo once daily for 48 weeks
All-Cause Mortality
E/C/F/TDF ATV+RTV+FTC/TDF
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
E/C/F/TDF ATV+RTV+FTC/TDF
Affected / at Risk (%) Affected / at Risk (%)
Total   24/289 (8.30%)   29/286 (10.14%) 
Blood and lymphatic system disorders     
Anaemia  1  0/289 (0.00%)  1/286 (0.35%) 
Iron deficiency anaemia  1  0/289 (0.00%)  1/286 (0.35%) 
Cardiac disorders     
Angina unstable  1  1/289 (0.35%)  0/286 (0.00%) 
Cardiomegaly  1  0/289 (0.00%)  1/286 (0.35%) 
Eye disorders     
Chalazion  1  0/289 (0.00%)  1/286 (0.35%) 
Gastrointestinal disorders     
Abdominal pain  1  0/289 (0.00%)  1/286 (0.35%) 
Gastritis  1  1/289 (0.35%)  0/286 (0.00%) 
Pancreatitis  1  1/289 (0.35%)  0/286 (0.00%) 
General disorders     
Malaise  1  1/289 (0.35%)  0/286 (0.00%) 
Hepatobiliary disorders     
Cholecystitis  1  1/289 (0.35%)  0/286 (0.00%) 
Cholecystitis acute  1  0/289 (0.00%)  1/286 (0.35%) 
Chronic hepatitis  1  1/289 (0.35%)  0/286 (0.00%) 
Drug-induced liver injury  1  0/289 (0.00%)  1/286 (0.35%) 
Infections and infestations     
Arthritis bacterial  1  1/289 (0.35%)  0/286 (0.00%) 
Catheter site infection  1  1/289 (0.35%)  0/286 (0.00%) 
Cellulitis  1  0/289 (0.00%)  1/286 (0.35%) 
Furuncle  1  0/289 (0.00%)  1/286 (0.35%) 
Gastroenteritis  1  1/289 (0.35%)  0/286 (0.00%) 
Gastroenteritis viral  1  0/289 (0.00%)  1/286 (0.35%) 
Malaria  1  1/289 (0.35%)  0/286 (0.00%) 
Ophthalmic herpes zoster  1  0/289 (0.00%)  1/286 (0.35%) 
Pelvic inflammatory disease  1  1/289 (0.35%)  0/286 (0.00%) 
Peritonitis  1  1/289 (0.35%)  1/286 (0.35%) 
Pneumonia  1  2/289 (0.69%)  1/286 (0.35%) 
Pulmonary tuberculosis  1  1/289 (0.35%)  0/286 (0.00%) 
Subcutaneous abscess  1  1/289 (0.35%)  0/286 (0.00%) 
Syphilis  1  0/289 (0.00%)  1/286 (0.35%) 
Injury, poisoning and procedural complications     
Fall  1  0/289 (0.00%)  1/286 (0.35%) 
Metabolism and nutrition disorders     
Dehydration  1  1/289 (0.35%)  0/286 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/289 (0.35%)  0/286 (0.00%) 
Arthritis  1  0/289 (0.00%)  1/286 (0.35%) 
Back pain  1  1/289 (0.35%)  0/286 (0.00%) 
Musculoskeletal chest pain  1  1/289 (0.35%)  0/286 (0.00%) 
Musculoskeletal pain  1  0/289 (0.00%)  2/286 (0.70%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cervix carcinoma  1  1/289 (0.35%)  0/286 (0.00%) 
Nervous system disorders     
Headache  1  1/289 (0.35%)  0/286 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous  1  2/289 (0.69%)  2/286 (0.70%) 
Ectopic pregnancy  1  1/289 (0.35%)  0/286 (0.00%) 
Imminent abortion  1  0/289 (0.00%)  1/286 (0.35%) 
Psychiatric disorders     
Depression  1  3/289 (1.04%)  1/286 (0.35%) 
Depression suicidal  1  1/289 (0.35%)  0/286 (0.00%) 
Stress  1  1/289 (0.35%)  0/286 (0.00%) 
Substance abuse  1  0/289 (0.00%)  1/286 (0.35%) 
Suicidal ideation  1  0/289 (0.00%)  1/286 (0.35%) 
Suicide attempt  1  0/289 (0.00%)  1/286 (0.35%) 
Renal and urinary disorders     
Renal failure acute  1  0/289 (0.00%)  2/286 (0.70%) 
Reproductive system and breast disorders     
Cervical dysplasia  1  1/289 (0.35%)  0/286 (0.00%) 
Dysfunctional uterine bleeding  1  0/289 (0.00%)  1/286 (0.35%) 
Uterine haemorrhage  1  0/289 (0.00%)  1/286 (0.35%) 
Vaginal haemorrhage  1  1/289 (0.35%)  1/286 (0.35%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  2/289 (0.69%)  0/286 (0.00%) 
Neonatal respiratory distress syndrome  1  0/289 (0.00%)  1/286 (0.35%) 
Pleurisy  1  0/289 (0.00%)  1/286 (0.35%) 
Skin and subcutaneous tissue disorders     
Erythema multiforme  1  0/289 (0.00%)  1/286 (0.35%) 
Stevens-Johnson syndrome  1  1/289 (0.35%)  1/286 (0.35%) 
Vascular disorders     
Hypotension  1  1/289 (0.35%)  0/286 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
E/C/F/TDF ATV+RTV+FTC/TDF
Affected / at Risk (%) Affected / at Risk (%)
Total   165/289 (57.09%)   183/286 (63.99%) 
Eye disorders     
Ocular icterus  1  1/289 (0.35%)  34/286 (11.89%) 
Gastrointestinal disorders     
Abdominal pain  1  16/289 (5.54%)  7/286 (2.45%) 
Diarrhoea  1  15/289 (5.19%)  19/286 (6.64%) 
Dyspepsia  1  13/289 (4.50%)  16/286 (5.59%) 
Nausea  1  42/289 (14.53%)  40/286 (13.99%) 
Vomiting  1  28/289 (9.69%)  17/286 (5.94%) 
Hepatobiliary disorders     
Jaundice  1  1/289 (0.35%)  30/286 (10.49%) 
Infections and infestations     
Influenza  1  19/289 (6.57%)  18/286 (6.29%) 
Malaria  1  33/289 (11.42%)  22/286 (7.69%) 
Nasopharyngitis  1  15/289 (5.19%)  14/286 (4.90%) 
Upper respiratory tract infection  1  47/289 (16.26%)  42/286 (14.69%) 
Urinary tract infection  1  20/289 (6.92%)  21/286 (7.34%) 
Vulvovaginal candidiasis  1  19/289 (6.57%)  19/286 (6.64%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  9/289 (3.11%)  21/286 (7.34%) 
Back pain  1  20/289 (6.92%)  18/286 (6.29%) 
Nervous system disorders     
Dizziness  1  16/289 (5.54%)  9/286 (3.15%) 
Headache  1  47/289 (16.26%)  42/286 (14.69%) 
Neuropathy peripheral  1  20/289 (6.92%)  20/286 (6.99%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  20/289 (6.92%)  18/286 (6.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
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: NCT01705574     History of Changes
Other Study ID Numbers: GS-US-236-0128
2012-003708-11 ( EudraCT Number )
First Submitted: October 10, 2012
First Posted: October 12, 2012
Results First Submitted: February 11, 2016
Results First Posted: March 10, 2016
Last Update Posted: October 30, 2018