Efficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment-Experienced Adults

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01967940
• Collaborator: (none)
• Enrollment: 55
• Locations: 15
• Arms: 4
• Actual Duration (Months): 45.2
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the efficacy of tenofovir alafenamide (TAF) versus placebo, each administered with the existing, failing antiretroviral (ARV) regimen. There are 2 parts to this study: Part 1 and Part 2.

Part 1 consists of 2 cohorts, starting with a sentinel cohort, in which participants will be enrolled to receive open-label TAF in addition to their current failing ARV regimen. This cohort will then be followed by a randomized, double-blind, cohort to compare the addition of TAF or placebo in HIV-1 positive adults who are failing their current ARV regimen.

In Part 2, all participants who complete Part 1 of the study will discontinue their failing ARV regimen and TAF or placebo for a 14-day washout period. Following the washout period, all participants who received TAF in Part 1 and have a > 0.5 log10 decline in HIV-1 RNA will receive elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen (STR) plus atazanavir (ATV) once daily for 48 weeks. Participants who received TAF who have a ≤ 0.5 log10 decline in HIV-1 RNA will be discontinued from the study and will not be eligible to continue into Part 2 of the study. All participants who received placebo in Part 1 will be eligible to participate in Part 2 regardless of their viral load change. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country.

Condition or Disease	Intervention/Treatment	Phase
HIV; HIV Infections; Acquired Immunodeficiency Syndrome	Drug: TAF; Drug: Placebo; Drug: E/C/F/TAF; Drug: Current failing ARV regimen; Drug: ATV	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Part 1 (Sentinel Cohort followed by a Randomized Cohort), 14-day washout period, then Part 2Part 1 (Sentinel Cohort followed by a Randomized Cohort), 14-day washout period, then Part 2
• Masking: Double (Participant, Investigator)
• Masking Description: Part 1 Sentinel Cohort: Open-label, non-randomized Part 1 Randomized Cohort: Double-blind, randomized Part 2: Open-label, non-randomized
• Primary Purpose: Treatment
• Official Title: A Phase 3, Two-Part Study to Evaluate the Efficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment-Experienced Adults
• Actual Study Start Date: Oct 25, 2013
• Actual Primary Completion Date: May 21, 2015
• Actual Study Completion Date: Jul 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Sentinel Cohort (TAF) TAF + their current failing ARV regimen for 10 days in Part 1	Drug: TAF; 25 mg tablet administered orally once daily with food; Other Names: Vemlidy® GS-7340 ; Drug: Current failing ARV regimen; Participants will continue taking their current ARV regimen as prescribed in Part 1.
Experimental: Part 1 Randomized Cohort (TAF) Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive TAF + their current failing ARV regimen for 10 days in Part 1.	Drug: TAF; 25 mg tablet administered orally once daily with food; Other Names: Vemlidy® GS-7340 ; Drug: Current failing ARV regimen; Participants will continue taking their current ARV regimen as prescribed in Part 1.
Placebo Comparator: Part 1 Randomized Cohort (Placebo) Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive placebo + their current failing ARV regimen for 10 days in Part 1.	Drug: Placebo; Tablets to match TAF administered orally once daily with food; Drug: Current failing ARV regimen; Participants will continue taking their current ARV regimen as prescribed in Part 1.
Experimental: Part 2 E/C/F/TAF+ATV Following a 14-day period to confirm eligibility, participants in the Randomized Cohort TAF group with a > 0.5 log10 decline in HIV-1 RNA and all participants completing the Randomized Cohort Placebo group will receive E/C/F/TAF+ATV for 48 weeks in Part 2. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country.	Drug: E/C/F/TAF; 150/150/200/10 mg STR administered orally once daily with food; Other Names: Genvoya® ; Drug: ATV; 300 mg tablet administered orally once daily.; Other Names: Reyataz®

Outcome Measures

Primary Outcome Measures

1. Part 1: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 10 [Day 10]

Secondary Outcome Measures

1. Part 1: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Day 10 [Baseline; Day 10]

2. Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 24 [Up to Week 24]

3. Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 48 [Up to Week 48]

4. Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 24 [Up to Week 24]

5. Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 48 [Up to Week 48]

6. Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24 [Week 24]

   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.

7. Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48 [Week 48]

   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.

8. Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24 [Week 24]

   The percentage of participants with HIV-1 RNA < 400 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.

9. Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48 [Week 48]

   The percentage of participants with HIV-1 RNA < 400 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.

10. Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 24 [Baseline; Week 24]

11. Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 48 [Baseline; Week 48]

12. Part 2: Change From Baseline in CD4+ Cell Count at Week 24 [Baseline; Week 24]

13. Part 2: Change From Baseline in CD4+ Cell Count at Week 48 [Baseline; Week 48]

14. Part 2: Change From Baseline in CD4+ Percentage at Week 24 [Baseline; Week 24]

15. Part 2: Change From Baseline in CD4+ Percentage at Week 48 [Baseline; Week 48]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures

• Currently taking a failing ARV regimen

• Plasma HIV-1 RNA ≥ 500 copies/mL but ≤ 100,000 copies/mL at screening

• Normal ECG

• Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance

• Alanine aminotransferase (AST)/aspartate aminotransferase (AST) ≤ 5 × the upper limit of the normal range (ULN)

• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin

• Adequate hematologic function

• Serum amylase ≤ 5 × ULN

• Females may enter the study if it is confirmed that she is:

• Not pregnant or nursing

• Of non-childbearing potential (ie, have had a hysterectomy, both ovaries removed, medically documented ovarian failure, or are postmenopausal women > 54 years of age with cessation [for ≥ 12 months] of previously occurring menses), or

• Of childbearing potential and agrees to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following study drug dosing

• Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.

• Males must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.

• Males must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.

Key Exclusion Criteria:

• A new AIDS-defining condition diagnosed within the 30 days prior to screening

• Hepatitis B surface antigen (HBsAg) positive

• Hepatitis C antibody positive (individuals with positive hepatitis C virus (HCV) antibody and without detectable HCV RNA are permitted to enroll)

• History of integrase inhibitor use

• Screening or historical genotype reports shows Q151M or T69ins or more than 3 TAMs.

• Screening or historical genotype report shows resistance to integrase inhibitors

• Individuals experiencing decompensated cirrhosis

• Current alcohol or substance use

• History of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Part 1, Day 1 and must not be anticipated to require systemic therapy during the study.

• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Part 1, Day 1

• Any other clinical condition or prior therapy that would make the individual unsuitable for the study or unable to comply with dosing requirements

• Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial

• Receiving ongoing therapy with any disallowed medications, including any drugs not to be used with elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide or known allergies to the excipients of E/C/F/TAF STR

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Midway Immunology and Research center	Fort Pierce	Florida	United States	34982
2	Triple O Research Institute, P.A.	West Palm Beach	Florida	United States	33401
3	Rowan Tree Medical, P.A.	Wilton Manors	Florida	United States	33305
4	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
5	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania	United States	19104
6	Salvador B Gautier Hospital - Infectious Diseases Department	Santo Domingo		Dominican Republic	10514
7	Instituto Dominicano de Estudio Virologicos - IDEV	Santo Domingo		Dominican Republic
8	Regional state budget health agency Krasnoyarsk Regional Center for Prevention and Control of AIDS	Krasnoyarsk		Russian Federation	660049
9	Center For Prevention and Treatment of AIDS and Infectious Diseases, Saint Petersburg	Saint Petersburg		Russian Federation	190020
10	The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)	Bangkok		Thailand	10330
11	Ramathibodi Hospital, Mahidol University	Bangkok		Thailand	10400
12	Siriraj Hospital Department of Preventive and Social Medicine, Faculty of Medicine	Bangkok		Thailand	10700
13	Chiang Mai University	Chiang Mai		Thailand	50200
14	Khon Kaen University	Khon Kaen		Thailand	40002
15	Joint Clinical Research Centre	Kampala		Uganda

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01967940
• Other Study ID Numbers: GS-US-292-0117; 2013-002830-19
• First Posted: Oct 23, 2013
• Last Update Posted: Nov 16, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Gilead Sciences: HIV-1; HIV; Treatment-Experienced
• Additional relevant MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Atazanavir Sulfate; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in the United States, Uganda, Thailand, Russian Federation, and Dominican Republic. The first participant was screened on 25 October 2013. The last study visit occurred on 31 July 2017.
Pre-assignment Detail	259 participants were screened.

Arm/Group Title	Part 1 Sentinel Cohort TAF	Part 1 Randomized Cohort TAF	Part 1 Randomized Cohort Placebo	Part 2 E/C/F/TAF + ATV
Arm/Group Description	Tenofovir alafenamide (TAF) 25 mg tablet once daily + their current failing regimen for 10 days	TAF 25 mg tablet once daily + their current failing regimen for 10 days	Placebo once daily + their current failing regimen for 10 days	Following a 14 day washout period, participants from the Randomized Cohort TAF group who had a > 0.5 log10 decline in HIV-1 RNA and participants from the Randomized Cohort Placebo group were eligible to receive elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) single-tablet regimen (STR) plus atazanavir (ATV) 300 mg once daily for 48 weeks. After completion of Part 2, all participants were eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF became commercially available, or until Gilead Sciences terminated development of E/C/F/TAF in the applicable country.
Period Title: Part 1
STARTED	12	28	15	0
COMPLETED	12	28	15	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1
STARTED	0	0	0	38
COMPLETED	0	0	0	35
NOT COMPLETED	0	0	0	3

Baseline Characteristics

Arm/Group Title	Part 1 Sentinel Cohort TAF	Part 1 Randomized Cohort TAF	Part 1 Randomized Cohort Placebo	Total
Arm/Group Description	TAF 25 mg tablet once daily + their current failing regimen for 10 days	TAF 25 mg tablet once daily + their current failing regimen for 10 days	Placebo once daily + their current failing regimen for 10 days	Total of all reporting groups
Overall Participants	12	28	15	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38 (7.3)	40 (9.1)	43 (8.2)	40 (8.6)
Sex: Female, Male (Count of Participants)
Female	3 25%	16 57.1%	4 26.7%	23 41.8%
Male	9 75%	12 42.9%	11 73.3%	32 58.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 41.7%	0 0%	1 6.7%	6 10.9%
Not Hispanic or Latino	7 58.3%	28 100%	14 93.3%	49 89.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	0 0%	5 17.9%	5 33.3%	10 18.2%
Black	3 25%	22 78.6%	9 60%	34 61.8%
White	4 33.3%	1 3.6%	0 0%	5 9.1%
Other	5 41.7%	0 0%	1 6.7%	6 10.9%
Region of Enrollment (participants) [Number]
Russian Federation	2 16.7%	1 3.6%	0 0%	3 5.5%
United States	5 41.7%	3 10.7%	0 0%	8 14.5%
Dominican Republic	5 41.7%	0 0%	1 6.7%	6 10.9%
Uganda	0 0%	19 67.9%	9 60%	28 50.9%
Thailand	0 0%	5 17.9%	5 33.3%	10 18.2%
HIV-1 RNA (log10 copies/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 copies/mL]	4.18 (0.648)	4.16 (0.544)	4.03 (0.953)	4.13 (0.688)
HIV-1 RNA Category (Count of Participants)
≤ 100,000 copies/mL	12 100%	27 96.4%	12 80%	51 92.7%
> 100,000 to ≤ 400,000 copies/mL	0 0%	1 3.6%	3 20%	4 7.3%
CD4 Cell Count (cells/µL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/µL]	269 (207.1)	245 (244.6)	232 (162.4)	246 (213.7)
CD4 Percentage (percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage]	17.4 (10.14)	16.5 (11.09)	14.3 (8.61)	16.1 (10.15)

Outcome Measures

1. Primary Outcome

Title	Part 1: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 10
Time Frame	Day 10

Outcome Measure Data

Analysis Population Description

Part 1 Full Analysis Set: participants who enrolled into Part 1 of the study and received at least one dose of study drug in Part 1.

Arm/Group Title	Part 1 Sentinel Cohort TAF	Part 1 Randomized Cohort TAF	Part 1 Randomized Cohort Placebo
Arm/Group Description	TAF 25 mg tablet once daily + their current failing regimen for 10 days	TAF 25 mg tablet once daily + their current failing regimen for 10 days	Placebo once daily + their current failing regimen for 10 days
Measure Participants	12	28	15
Number [percentage of participants]	58.3 485.8%	60.7 216.8%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1 Randomized Cohort TAF, Part 1 Randomized Cohort Placebo
	Comments	A sample size of 90 participants, randomized in a 2:1 ratio, achieves 89% power to detect a 35% difference in the proportion of participants with HIV-1 RNA decreases from baseline exceeding 0.5 log10 between the TAF and placebo arms at Day 10. Sample size and power computation was based on the assumption that 50% of participants in the TAF arm and 15% of participants in the placebo arm achieved a reduction exceeding 0.5 log10 HIV-1 RNA.
	Type of Statistical Test	Superiority
	Comments	Enrollment into this study was stopped early due to the challenge of recruiting a sufficient number of participants who met the eligibility criteria. The actual number of enrolled is 55, among them 43 enrolled in the Randomized Cohort. Based on the actual enrollment numbers, the power to detect a 35% difference drops to 51%, under the same assumptions in the original sample size calculations.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	60.7
	Confidence Interval	(2-Sided) 95%; 42.6 to 78.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval was estimated based on unconditional exact method using 2 inverted 1-sided tests with the standardized statistic.

2. Secondary Outcome

Title	Part 1: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Day 10
Time Frame	Baseline; Day 10

Outcome Measure Data

Analysis Population Description

Part 1 Full Analysis Set

Arm/Group Title	Part 1 Sentinel Cohort TAF	Part 1 Randomized Cohort TAF	Part 1 Randomized Cohort Placebo
Arm/Group Description	TAF 25 mg tablet once daily + their current failing regimen for 10 days	TAF 25 mg tablet once daily + their current failing regimen for 10 days	Placebo once daily + their current failing regimen for 10 days
Measure Participants	12	28	15
Mean (Standard Deviation) [log10 copies/mL]	-0.72 (0.574)	-0.70 (0.628)	-0.04 (0.233)

3. Secondary Outcome

Title	Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 24
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

Part 2 Safety Analysis Set: participants who enrolled into Part 2 of the study and received at least one dose of study drug in Part 2.

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	37
Number [percentage of participants]	37.8 315%

4. Secondary Outcome

Title	Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 48
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Part 2 Safety Analysis Set

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	37
Number [percentage of participants]	48.6 405%

5. Secondary Outcome

Title	Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 24
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

Part 2 Safety Analysis Set

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	37
Number [percentage of participants]	75.7 630.8%

6. Secondary Outcome

Title	Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 48
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Part 2 Safety Analysis Set

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	37
Number [percentage of participants]	81.1 675.8%

7. Secondary Outcome

Title	Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24
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

Outcome Measure Data

Analysis Population Description

Part 2 Full Analysis Set

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	37
Number [percentage of participants]	86.5 720.8%

8. Secondary Outcome

Title	Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48
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

Outcome Measure Data

Analysis Population Description

Part 2 Full Analysis Set: participants who enrolled into Part 2 of the study and received at least one dose of study drug in Part 2.

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	37
Number [percentage of participants]	97.3 810.8%

9. Secondary Outcome

Title	Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24
Description	The percentage of participants with HIV-1 RNA < 400 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

Outcome Measure Data

Analysis Population Description

Part 2 Full Analysis Set

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	37
Number [percentage of participants]	94.6 788.3%

10. Secondary Outcome

Title	Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48
Description	The percentage of participants with HIV-1 RNA < 400 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

Outcome Measure Data

Analysis Population Description

Part 2 Full Analysis Set

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	37
Number [percentage of participants]	97.3 810.8%

11. Secondary Outcome

Title	Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 24
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Part 2 Full Analysis Set with available data were analyzed.

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	35
Mean (Standard Deviation) [log10 copies/mL]	-2.96 (0.754)

12. Secondary Outcome

Title	Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 48
Time Frame	Baseline; Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Part 2 Full Analysis Set with available data were analyzed.

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	35
Mean (Standard Deviation) [log10 copies/mL]	-3.04 (0.594)

13. Secondary Outcome

Title	Part 2: Change From Baseline in CD4+ Cell Count at Week 24
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Part 2 Full Analysis Set with available data were analyzed.

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	35
Mean (Standard Deviation) [cells/μL]	76 (92.8)

14. Secondary Outcome

Title	Part 2: Change From Baseline in CD4+ Cell Count at Week 48
Time Frame	Baseline; Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Part 2 Full Analysis Set with available data were analyzed.

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	35
Mean (Standard Deviation) [cells/μL]	125 (109.0)

15. Secondary Outcome

Title	Part 2: Change From Baseline in CD4+ Percentage at Week 24
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Part 2 Full Analysis Set with available data were analyzed.

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	35
Mean (Standard Deviation) [percentage change]	4.4 (2.35)

16. Secondary Outcome

Title	Part 2: Change From Baseline in CD4+ Percentage at Week 48
Time Frame	Baseline; Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Part 2 Full Analysis Set with available data were analyzed.

Arm/Group Title	Part 2 E/C/F/TAF + ATV
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks
Measure Participants	35
Mean (Standard Deviation) [percentage change]	5.7 (2.99)

Adverse Events

Time Frame	Baseline up to the last dose date plus 30 days (average exposure: Part 1 = 10 days; Part 2 = 86.5 weeks)
Adverse Event Reporting Description	Safety Analysis Set: participants who enrolled into the study and received at least one dose of study drug.
Arm/Group Title	Part 1 Sentinel Cohort TAF		Part 1 Randomized Cohort TAF		Part 1 Randomized Cohort Placebo		Part 2 E/C/F/TAF + ATV
Arm/Group Description	TAF 25 mg tablet once daily + their current failing regimen for 10 days		TAF 25 mg tablet once daily + their current failing regimen for 10 days		Placebo once daily + their current failing regimen for 10 days		E/C/F/TAF (150/150/200/10 mg) STR plus ATV 300 mg once daily for 48 weeks plus the extension phase
All Cause Mortality
	Part 1 Sentinel Cohort TAF		Part 1 Randomized Cohort TAF		Part 1 Randomized Cohort Placebo		Part 2 E/C/F/TAF + ATV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/28 (0%)		0/15 (0%)		0/37 (0%)
Serious Adverse Events
	Part 1 Sentinel Cohort TAF		Part 1 Randomized Cohort TAF		Part 1 Randomized Cohort Placebo		Part 2 E/C/F/TAF + ATV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		3/28 (10.7%)		0/15 (0%)		4/37 (10.8%)
Gastrointestinal disorders
Enlarged uvula	0/12 (0%)		0/28 (0%)		0/15 (0%)		1/37 (2.7%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/12 (0%)		0/28 (0%)		0/15 (0%)		1/37 (2.7%)
Metabolism and nutrition disorders
Hypoglycaemia	0/12 (0%)		1/28 (3.6%)		0/15 (0%)		0/37 (0%)
Musculoskeletal and connective tissue disorders
Myopathy	0/12 (0%)		1/28 (3.6%)		0/15 (0%)		0/37 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/12 (0%)		1/28 (3.6%)		0/15 (0%)		0/37 (0%)
Skin and subcutaneous tissue disorders
Angioedema	0/12 (0%)		0/28 (0%)		0/15 (0%)		1/37 (2.7%)
Vascular disorders
Hypotension	0/12 (0%)		0/28 (0%)		0/15 (0%)		1/37 (2.7%)
Other (Not Including Serious) Adverse Events
	Part 1 Sentinel Cohort TAF		Part 1 Randomized Cohort TAF		Part 1 Randomized Cohort Placebo		Part 2 E/C/F/TAF + ATV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/12 (58.3%)		6/28 (21.4%)		5/15 (33.3%)		26/37 (70.3%)
Blood and lymphatic system disorders
Anaemia	0/12 (0%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Gastrointestinal disorders
Diarrhoea	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Haemorrhoids	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		0/37 (0%)
Nausea	2/12 (16.7%)		1/28 (3.6%)		0/15 (0%)		0/37 (0%)
Proctalgia	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		0/37 (0%)
Toothache	0/12 (0%)		0/28 (0%)		1/15 (6.7%)		3/37 (8.1%)
General disorders
Chest pain	0/12 (0%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Malaise	0/12 (0%)		0/28 (0%)		1/15 (6.7%)		1/37 (2.7%)
Pyrexia	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/12 (0%)		1/28 (3.6%)		0/15 (0%)		3/37 (8.1%)
Jaundice	0/12 (0%)		1/28 (3.6%)		0/15 (0%)		3/37 (8.1%)
Infections and infestations
Bacterial infection	0/12 (0%)		0/28 (0%)		1/15 (6.7%)		0/37 (0%)
Disseminated tuberculosis	0/12 (0%)		0/28 (0%)		1/15 (6.7%)		0/37 (0%)
Gastroenteritis	0/12 (0%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Influenza	0/12 (0%)		1/28 (3.6%)		0/15 (0%)		3/37 (8.1%)
Malaria	0/12 (0%)		0/28 (0%)		0/15 (0%)		5/37 (13.5%)
Oral candidiasis	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		1/37 (2.7%)
Pyuria	0/12 (0%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Tonsillitis	0/12 (0%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Upper respiratory tract infection	0/12 (0%)		1/28 (3.6%)		0/15 (0%)		11/37 (29.7%)
Urinary tract infection	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Viral upper respiratory tract infection	0/12 (0%)		1/28 (3.6%)		0/15 (0%)		2/37 (5.4%)
Injury, poisoning and procedural complications
Epicondylitis	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		0/37 (0%)
Limb injury	0/12 (0%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Metabolism and nutrition disorders
Hyperglycaemia	0/12 (0%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		1/37 (2.7%)
Back pain	0/12 (0%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Nervous system disorders
Dizziness	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		1/37 (2.7%)
Headache	0/12 (0%)		0/28 (0%)		0/15 (0%)		4/37 (10.8%)
Neuropathy peripheral	0/12 (0%)		1/28 (3.6%)		1/15 (6.7%)		3/37 (8.1%)
Psychiatric disorders
Insomnia	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		1/37 (2.7%)
Renal and urinary disorders
Nephrolithiasis	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		1/37 (2.7%)
Reproductive system and breast disorders
Dysmenorrhoea	0/12 (0%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Respiratory, thoracic and mediastinal disorders
Cough	0/12 (0%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Dyspnoea	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		0/37 (0%)
Oropharyngeal pain	0/12 (0%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Skin and subcutaneous tissue disorders
Eosinophilic cellulitis	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		0/37 (0%)
Rash	1/12 (8.3%)		0/28 (0%)		0/15 (0%)		2/37 (5.4%)
Vascular disorders
Hypertension	0/12 (0%)		0/28 (0%)		1/15 (6.7%)		1/37 (2.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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