Study to Evaluate Switching From Regimens Consisting of a Nonnucleoside Reverse Transcriptase Inhibitor Plus Emtricitabine and Tenofovir DF to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients

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ClinicalTrials.gov Identifier: NCT01495702

Recruitment Status : Completed

First Posted : December 20, 2011

Results First Posted : January 26, 2015

Last Update Posted : January 7, 2016

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
Conditions	Acquired Immunodeficiency Syndrome HIV Infections
Interventions	Drug: NNRTI Drug: FTC/TDF Drug: Stribild
Enrollment	439

Participant Flow

Recruitment Details	Participants were enrolled at study sites in North America, Europe, and Australia. The first participant was screened on 13 December 2011. The last study visit occurred on 01 December 2014.
Pre-assignment Details	571 participants were screened.


Arm/Group Title	Stribild	NNRTI+FTC/TDF
Arm/Group Description	Participants switched from their ba...	Participants stayed on their baseli...
Arm/Group Description	Participants switched from their baseline treatment regimen to Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate; E/C/F/TDF) (150/150/200/300 mg) single-tablet regimen (STR) once daily for up to 96 weeks in the randomized phase, and may have continued to receive Stribild in the extension phase.	Participants stayed on their baseline treatment regimen consisting of an nonnucleoside reverse transcriptase inhibitor (NNRTI) (efavirenz (EFV), nevirapine (NVP), or rilpivirine (RPV)) plus emtricitabine (FTC)/TDF (200/300 mg) (administered according to prescribing information) for up to 96 weeks in the randomized phase, and may have switched to Stribild in the extension phase.
Period Title: Randomized Phase
Started	292	147
Completed	266	119
Not Completed	26	28
Reason Not Completed
Randomized But Not Treated	1	4
Adverse Event	2	2
Death	1	0
Lack of Efficacy	2	0
Investigators Discretion	2	0
Withdrew Consent	10	18
Lost to Follow-up	4	3
Participant Noncompliance	1	0
Protocol Violation	3	1
Period Title: Extension Phase
Started	26	2
Completed	26	2
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Stribild	NNRTI+FTC/TDF	Total
Arm/Group Description		Participants switched from their ba...	Participants stayed on their baseli...	Total of all reporting groups
Arm/Group Description		Participants switched from their baseline treatment regimen to Stribild (E/C/F/TDF) (150/150/200/300 mg) STR once daily for up to 96 weeks in the randomized phase, and may have continued to receive Stribild in the extension phase.	Participants stayed on their baseline treatment regimen consisting of an NNRTI (EFV, NVP, or RPV) plus FTC/TDF (200/300 mg) (administered according to prescribing information) for up to 96 weeks in the randomized phase, and may have switched to Stribild in the extension phase.	Total of all reporting groups
Overall Number of Baseline Participants		291	143	434
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Safety Analysis Set: participants were randomized and received at least one dose of study drug
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	291 participants	143 participants	434 participants
		42 (9.6)	40 (9.7)	41 (9.7)
Age, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	291 participants	143 participants	434 participants
< 40 years		114	74	188
≥ 40 to < 50 years		106	44	150
≥ 50 years		71	25	96
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	291 participants	143 participants	434 participants
	Female	23 7.9%	9 6.3%	32 7.4%
	Male	268 92.1%	134 93.7%	402 92.6%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	291 participants	143 participants	434 participants
American Indian or Alaska Native		2	0	2
Asian		4	9	13
Black or African Heritage		49	23	72
Native Hawaiian or Pacific Islander		1	0	1
White		231	109	340
Other		4	2	6
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	291 participants	143 participants	434 participants
Hispanic/Latino		30	16	46
Non-Hispanic/Latino		261	127	388
Not Permitted		0	0	0
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	291 participants	143 participants	434 participants
France		4	1	5
Portugal		2	4	6
United States		152	75	227
Puerto Rico		4	2	6
Canada		13	6	19
Spain		27	13	40
Belgium		14	7	21
Austria		6	3	9
Australia		8	4	12
Germany		24	10	34
United Kingdom		13	5	18
Italy		24	13	37
HIV-1 RNA Category Measure Type: Number Unit of measure: Participants	Number Analyzed	291 participants	143 participants	434 participants
< 50 copies/mL		285	141	426
50 to < 200 copies/mL		4	2	6
200 to < 400 copies/mL		0	0	0
≥ 400 copies/mL		2	0	2
CD4+ Cell Count Mean (Standard Deviation) Unit of measure: cells/µL
	Number Analyzed	291 participants	143 participants	434 participants
		586 (210.3)	593 (224.6)	588 (214.9)
CD4+ Cell Count Category Measure Type: Number Unit of measure: Participants	Number Analyzed	291 participants	143 participants	434 participants
≤ 50 cells/µL		0	0	0
51 to ≤ 200 cells/µL		4	1	5
201 to ≤ 350 cells/µL		26	20	46
351 to ≤ 500 cells/µL		75	33	108
> 500 cells/µL		186	89	275
HIV Disease Status Measure Type: Number Unit of measure: Participants	Number Analyzed	291 participants	143 participants	434 participants
Asymptomatic		225	115	340
Symptomatic HIV Infections		36	14	50
AIDS		30	14	44

Outcome Measures

1.Primary Outcome


Title	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
Description	The FDA-defined Snapshot algorithm was used, which defines a patient's...
Description	The FDA-defined 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.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants were randomized, received at least 1 dose of study drug, had no documented resistance, and were on an NNRTI at screening


Arm/Group Title	Stribild	NNRTI+FTC/TDF
Arm/Group Description:	Participants switched from their ba...	Participants stayed on their baseli...
Arm/Group Description:	Participants switched from their baseline treatment regimen to Stribild (E/C/F/TDF) (150/150/200/300 mg) STR once daily for up to 96 weeks in the randomized phase, and may have continued to receive Stribild in the extension phase.	Participants stayed on their baseline treatment regimen consisting of an NNRTI (EFV, NVP, or RPV) plus FTC/TDF (200/300 mg) (administered according to prescribing information) for up to 96 weeks in the randomized phase, and may have switched to Stribild in the extension phase.
Overall Number of Participants Analyzed	290	143
Measure Type: Number Unit of Measure: percentage of participants
	93.4	88.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stribild, NNRTI+FTC/TDF
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The null hypothesis was that the Stribild group was at least 12% worse than the NNRTI+FTC/TDF group with respect to the percentage of participants maintaining HIV-1 RNA < 50 copies/mL at Week 48. The alternative hypothesis was that the Stribild group was less than 12% worse than the NNRTI+FTC/TDF group.

Statistical Test of Hypothesis	P-Value	0.066
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	5.3
	Confidence Interval	(2-Sided) 95% -0.5 to 12.0
	Estimation Comments	The 95% confidence interval (CI) for the difference was from unconditional exact method using 2 inverted 1-sided tests with the standardized statistic using StatXact.

2.Secondary Outcome


Title	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96
Description	The FDA-defined Snapshot algorithm was used, which defines a patient's...
Description	The FDA-defined 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.
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

Full Analysis Set


Arm/Group Title	Stribild	NNRTI+FTC/TDF
Arm/Group Description:	Participants switched from their ba...	Participants stayed on their baseli...
Arm/Group Description:	Participants switched from their baseline treatment regimen to Stribild (E/C/F/TDF) (150/150/200/300 mg) STR once daily for up to 96 weeks in the randomized phase, and may have continued to receive Stribild in the extension phase.	Participants stayed on their baseline treatment regimen consisting of an NNRTI (EFV, NVP, or RPV) plus FTC/TDF (200/300 mg) (administered according to prescribing information) for up to 96 weeks in the randomized phase, and may have switched to Stribild in the extension phase.
Overall Number of Participants Analyzed	290	143
Measure Type: Number Unit of Measure: percentage of participants
	86.6	80.4

3.Secondary Outcome


Title	Change From Baseline in CD4+ Cell Count at Week 48
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline; Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed; the missing-equals-excluded approach where participants with missing data were excluded from the analysis.


Arm/Group Title	Stribild	NNRTI+FTC/TDF
Arm/Group Description:	Participants switched from their ba...	Participants stayed on their baseli...
Arm/Group Description:	Participants switched from their baseline treatment regimen to Stribild (E/C/F/TDF) (150/150/200/300 mg) STR once daily for up to 96 weeks in the randomized phase, and may have continued to receive Stribild in the extension phase.	Participants stayed on their baseline treatment regimen consisting of an NNRTI (EFV, NVP, or RPV) plus FTC/TDF (200/300 mg) (administered according to prescribing information) for up to 96 weeks in the randomized phase, and may have switched to Stribild in the extension phase.
Overall Number of Participants Analyzed	270	126
Mean (Standard Deviation) Unit of Measure: cells/µL
	56 (147.3)	58 (179.3)

4.Secondary Outcome


Title	Change From Baseline in CD4+ Cell Count at Week 96
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline; Week 96

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data while on study drug were analyzed; the missing-equals-excluded approach where participants with missing data were excluded from the analysis.


Arm/Group Title	Stribild	NNRTI+FTC/TDF
Arm/Group Description:	Participants switched from their ba...	Participants stayed on their baseli...
Arm/Group Description:	Participants switched from their baseline treatment regimen to Stribild (E/C/F/TDF) (150/150/200/300 mg) STR once daily for up to 96 weeks in the randomized phase, and may have continued to receive Stribild in the extension phase.	Participants stayed on their baseline treatment regimen consisting of an NNRTI (EFV, NVP, or RPV) plus FTC/TDF (200/300 mg) (administered according to prescribing information) for up to 96 weeks in the randomized phase, and may have switched to Stribild in the extension phase.
Overall Number of Participants Analyzed	256	116
Mean (Standard Deviation) Unit of Measure: cells/µL
	83 (166.7)	101 (156.5)

Adverse Events

Time Frame	Baseline through end of study (average 90 weeks)
Adverse Event Reporting Description	Safety Analysis Set participants were randomized and received at least 1 dose of study drug

Arm/Group Title	Stribild (Randomized Phase)	NNRTI+FTC/TDF (Randomized Phase)	All Stribild
Arm/Group Description	Adverse events for this reporting g...	Adverse events for this reporting g...	Adverse events for this reporting g...
Arm/Group Description	Adverse events for this reporting group include those occurring in participants receiving Stribild in the randomized phase. Participants switched from their baseline treatment regimen to Stribild (E/C/F/TDF) (150/150/200/300 mg) STR once daily for up to 96 weeks in the randomized phase, and may have continued to receive Stribild in the extension phase.	Adverse events for this reporting group include those occurring in participants receiving NNRTI+FTC/TDF in the randomized phase. Participants stayed on their baseline treatment regimen consisting of an NNRTI (EFV, NVP, or RPV) plus FTC/TDF (200/300 mg) (administered according to prescribing information) for up to 96 weeks in the randomized phase, and may have switched to Stribild in the extension phase.	Adverse events for this reporting group include those occurring in all participants while receiving Stribild in the randomized and extension phases.
All-Cause Mortality
	Stribild (Randomized Phase)	NNRTI+FTC/TDF (Randomized Phase)	All Stribild
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Stribild (Randomized Phase)	NNRTI+FTC/TDF (Randomized Phase)	All Stribild
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	24/291 (8.25%)	7/143 (4.90%)	26/293 (8.87%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Febrile neutropenia ^† 1	0/291 (0.00%)	0/143 (0.00%)	1/293 (0.34%)
Lymphadenopathy ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Cardiac disorders
Coronary artery stenosis ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Myocardial infarction ^† 1	1/291 (0.34%)	2/143 (1.40%)	1/293 (0.34%)
Myocardial ischaemia ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Gastrointestinal disorders
Colitis ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Diarrhoea ^† 1	0/291 (0.00%)	1/143 (0.70%)	0/293 (0.00%)
Gastritis ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Nausea ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
General disorders
Chest pain ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Pyrexia ^† 1	0/291 (0.00%)	1/143 (0.70%)	0/293 (0.00%)
Hepatobiliary disorders
Bile duct stone ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Immune system disorders
Drug hypersensitivity ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Hypersensitivity ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Infections and infestations
Appendicitis ^† 1	0/291 (0.00%)	2/143 (1.40%)	0/293 (0.00%)
Gastroenteritis ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Pneumonia ^† 1	0/291 (0.00%)	1/143 (0.70%)	0/293 (0.00%)
Pyelonephritis ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Septic shock ^† 1	1/291 (0.34%)	1/143 (0.70%)	1/293 (0.34%)
Shigella infection ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Staphylococcal infection ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Urosepsis ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Injury, poisoning and procedural complications
Alcohol poisoning ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Joint dislocation ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Laceration ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Rib fracture ^† 1	0/291 (0.00%)	1/143 (0.70%)	0/293 (0.00%)
Musculoskeletal and connective tissue disorders
Osteoarthritis ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer ^† 1	0/291 (0.00%)	0/143 (0.00%)	1/293 (0.34%)
Lung neoplasm malignant ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Metastases to liver ^† 1	0/291 (0.00%)	0/143 (0.00%)	1/293 (0.34%)
Nervous system disorders
Cerebrovascular accident ^† 1	0/291 (0.00%)	1/143 (0.70%)	0/293 (0.00%)
Psychomotor hyperactivity ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Syncope ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Psychiatric disorders
Completed suicide ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Delusion ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Drug abuse ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Stress ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Substance-induced psychotic disorder ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Suicidal ideation ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Suicide attempt ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Renal and urinary disorders
Renal failure acute ^† 1	1/291 (0.34%)	1/143 (0.70%)	1/293 (0.34%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Haemoptysis ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Pleural effusion ^† 1	0/291 (0.00%)	1/143 (0.70%)	0/293 (0.00%)
Pulmonary embolism ^† 1	0/291 (0.00%)	1/143 (0.70%)	0/293 (0.00%)
Respiratory failure ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
Vascular disorders
Deep vein thrombosis ^† 1	0/291 (0.00%)	1/143 (0.70%)	0/293 (0.00%)
Hypertensive crisis ^† 1	0/291 (0.00%)	1/143 (0.70%)	0/293 (0.00%)
Hypotension ^† 1	1/291 (0.34%)	0/143 (0.00%)	1/293 (0.34%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (17.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Stribild (Randomized Phase)	NNRTI+FTC/TDF (Randomized Phase)	All Stribild
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	154/291 (52.92%)	66/143 (46.15%)	154/293 (52.56%)
Gastrointestinal disorders
Diarrhoea ^† 1	30/291 (10.31%)	11/143 (7.69%)	30/293 (10.24%)
Nausea ^† 1	24/291 (8.25%)	4/143 (2.80%)	24/293 (8.19%)
General disorders
Fatigue ^† 1	19/291 (6.53%)	2/143 (1.40%)	19/293 (6.48%)
Infections and infestations
Nasopharyngitis ^† 1	30/291 (10.31%)	17/143 (11.89%)	30/293 (10.24%)
Sinusitis ^† 1	21/291 (7.22%)	5/143 (3.50%)	21/293 (7.17%)
Syphilis ^† 1	17/291 (5.84%)	10/143 (6.99%)	17/293 (5.80%)
Upper respiratory tract infection ^† 1	33/291 (11.34%)	15/143 (10.49%)	33/293 (11.26%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	19/291 (6.53%)	5/143 (3.50%)	19/293 (6.48%)
Back pain ^† 1	23/291 (7.90%)	8/143 (5.59%)	23/293 (7.85%)
Nervous system disorders
Headache ^† 1	29/291 (9.97%)	8/143 (5.59%)	29/293 (9.90%)
Psychiatric disorders
Insomnia ^† 1	22/291 (7.56%)	11/143 (7.69%)	22/293 (7.51%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	24/291 (8.25%)	5/143 (3.50%)	24/293 (8.19%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (17.1)

Limitations and Caveats

There were no limitations affecting the analysis or results.

More Information

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:	Clinical Trial Disclosures
Organization:	Gilead Sciences, Inc.
EMail:	ClinicalTrialDisclosures@gilead.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pozniak A, Flamm J, Antinori A, Bloch M, Ward D, Berenguer J, Cote P, Andreatta K, Garner W, Szwarcberg J, Nguyen-Cleary T, McColl DJ, Piontkowsky D. Switching to the single-tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir DF from non-nucleoside reverse transcriptase inhibitor plus coformulated emtricitabine and tenofovir DF regimens: Week 96 results of STRATEGY-NNRTI. HIV Clin Trials. 2017 Jul;18(4):141-148. doi: 10.1080/15284336.2017.1338844. Epub 2017 Jul 9.

Pozniak A, Markowitz M, Mills A, Stellbrink HJ, Antela A, Domingo P, Girard PM, Henry K, Nguyen T, Piontkowsky D, Garner W, White K, Guyer B. Switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of non-nucleoside reverse transcriptase inhibitor with emtricitabine and tenofovir in virologically suppressed adults with HIV (STRATEGY-NNRTI): 48 week results of a randomised, open-label, phase 3b non-inferiority trial. Lancet Infect Dis. 2014 Jul;14(7):590-9. doi: 10.1016/S1473-3099(14)70796-0. Epub 2014 Jun 5.

Layout table for additonal information

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01495702
Other Study ID Numbers:	GS-US-236-0121 2011-004963-56 ( EudraCT Number )
First Submitted:	December 14, 2011
First Posted:	December 20, 2011
Results First Submitted:	December 31, 2014
Results First Posted:	January 26, 2015
Last Update Posted:	January 7, 2016

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