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Clinical Trial Results:
A Phase 3 Randomized, Open Label Study to Evaluate Switching from Regimens Consisting of a Ritonavir-boosted Protease Inhibitor and Two Nucleoside Reverse Transcriptase Inhibitors to Emtricitabine/Rilpivirine/ Tenofovir Disoproxil Fumarate (FTC/RPV/TDF) Fixed-dose Regimen in Virologically Suppressed, HIV-1 Infected Patients

Summary
EudraCT number	2010-023178-37
Trial protocol	GB DE ES BE IT AT
Global end of trial date	28 Oct 2014

Results information
Results version number	v1(current)
This version publication date	05 Jun 2016
First version publication date	05 Jun 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GS-US-264-0106

ISRCTN number

US NCT number

NCT01252940

WHO universal trial number (UTN)

Sponsor organisation name

Gilead Sciences

Sponsor organisation address

333 Lakeside Drive, Foster City, CA, United States, 94404

Public contact

Clinical Trial Mailbox, Gilead Sciences International Ltd, ClinicalTrialDisclosures@gilead.com

Scientific contact

Clinical Trial Mailbox, Gilead Sciences International Ltd, ClinicalTrialDisclosures@gilead.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

28 Oct 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Oct 2014

Was the trial ended prematurely?

Main objective of the trial

To evaluate the non-inferiority of emtricitabine 200 mg/rilpivirine 25 mg/tenofovir disoproxil fumarate 300 mg (FTC/RPV/TDF) formulated as a single-tablet regimen (STR) and taken once daily relative to regimens consisting of a ritonavir-boosted protease inhibitor (PI/r) and 2 nucleoside reverse transcriptase inhibitors (NRTIs) in maintaining HIV-1 RNA < 50 copies/mL at Week 24.

Protection of trial subjects

The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Nov 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 20

Country: Number of subjects enrolled

United Kingdom: 23

Country: Number of subjects enrolled

Austria: 26

Country: Number of subjects enrolled

Belgium: 28

Country: Number of subjects enrolled

France: 43

Country: Number of subjects enrolled

Germany: 43

Country: Number of subjects enrolled

Italy: 26

Country: Number of subjects enrolled

Canada: 25

Country: Number of subjects enrolled

Puerto Rico: 18

Country: Number of subjects enrolled

United States: 230

Worldwide total number of subjects

482

EEA total number of subjects

209

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

477

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants were enrolled at 110 sites in the North America and Europe. The first participant was screened on 17 November 2010. The last participant observation was on 28 October 2014.

Screening details

617 participants were screened.

Period 1 title

Main Study Phase

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

FTC/RPV/TDF

Arm description

Participants were randomized to switch from their existing treatment regimen to the emtricitabine (FTC)/rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF) single-tablet regimen (STR) at the beginning of the study.

Arm type

Experimental

Investigational medicinal product name

Emtricitabine/rilpivirine/tenofovir disoproxil fumarate

Investigational medicinal product code

Other name

Complera®, Eviplera®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) 200/25/300 mg single-tablet regimen (STR) administered orally with a meal once daily

SBR/Delayed Switch

Arm description

Participants were randomized to stay on their existing treatment regimen (Stay on Baseline Regimen (SBR)) at the beginning of the study through Week 24, and switch to the FTC/RPV/TDF STR (Delayed Switch) at the Week 24 visit. Their existing treatment regimen consisted of protease inhibitor (PI) + ritonavir (RTV) + 2 two nucleoside reverse transcriptase inhibitors (NRTIs). Protease inhibitors (PIs) may have included amprenavir, atazanavir, darunavir, fosamprenavir, Kaletra (lopinavir/ritonavir, coformulated), ritonavir, and saquinavir. PIs were administered according to prescribing information. Ritonavir (RTV) was administered according to prescribing information. NRTIs may have included abacavir, emtricitabine, Combivir (lamivudine/zidovudine, coformulated), Epzicom (abacavir/lamivudine, coformulated), lamivudine, stavudine, tenofovir DF, Truvada® (emtricitabine/tenofovir DF, coformulated), and zidovudine. NRTIs were administered according to prescribing information.

Arm type

Experimental

Investigational medicinal product name

Emtricitabine/rilpivirine/tenofovir disoproxil fumarate

Investigational medicinal product code

Other name

Complera®, Eviplera®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

FTC/RPV/TDF 200/25/300 mg STR administered orally with a meal once daily

Number of subjects in period 1 ^[1]	FTC/RPV/TDF	SBR/Delayed Switch
Started	317	159
Completed 24 Weeks (SBR/Delayed Switch)	0 ^[2]	153
Completed	295	149
Not completed	22	10
Physician decision	1	-
Adverse event, non-fatal	3	1
Subject Non-compliance	1	1
Withdrawal by Subject	6	5
Protocol Violation	4	2
Lost to follow-up	6	1
Lack of efficacy	1	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 6 participants who were randomized but not treated are not included in the subject disposition table. NOTE: For the SBR/Delayed Switch group, 152 participants switched regimens at Week 24. Discontinuations after switch: withdrawal by subject = 2; adverse event = 1; and protocol violation = 1.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This milestone only applies to the SBR/Delayed Switch group.

Period 2 title

Extension Phase

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

FTC/RPV/TDF

Arm description

Participants were randomized to switch from their existing treatment regimen to the FTC/RPV/TDF STR at the beginning of the study. Following Week 48, participants may have continued to receive FTC/RPV/TDF STR per protocol before switching to a commercially available source.

Arm type

Experimental

Investigational medicinal product name

Emtricitabine/rilpivirine/tenofovir disoproxil fumarate

Investigational medicinal product code

Other name

Complera®, Eviplera®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

FTC/RPV/TDF 200/25/300 mg STR administered orally with a meal once daily

SBR/Delayed Switch

Arm description

Participants were randomized to stay on their existing treatment regimen at the beginning of the study through Week 24, and switch to the FTC/RPV/TDF STR (Delayed Switch) at the Week 24 visit. Their existing treatment regimen consisted of PI+RTV+ 2 two NRTIs. PIs may have included amprenavir, atazanavir, darunavir, fosamprenavir, Kaletra (lopinavir/ritonavir, coformulated), ritonavir, and saquinavir. PIs were administered according to prescribing information. RTV was administered according to prescribing information. NRTIs may have included abacavir, emtricitabine, Combivir (lamivudine/zidovudine, coformulated), Epzicom (abacavir/lamivudine, coformulated), lamivudine, stavudine, tenofovir DF, Truvada® (emtricitabine/tenofovir DF, coformulated), and zidovudine. NRTIs were administered according to prescribing information. Following Week 48, participants may have continued to receive FTC/RPV/TDF STR per protocol before switching to a commercially available source.

Arm type

Experimental

Investigational medicinal product name

Emtricitabine/rilpivirine/tenofovir disoproxil fumarate

Investigational medicinal product code

Other name

Complera®, Eviplera®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

FTC/RPV/TDF 200/25/300 mg STR administered orally with a meal once daily

Number of subjects in period 2 ^[3]	FTC/RPV/TDF	SBR/Delayed Switch
Started	110	49
Completed	100	46
Not completed	10	3
Physician decision	-	1
Adverse event, non-fatal	2	1
Subject Non-compliance	1	-
Withdrawal by Subject	1	1
Lost to follow-up	5	-
Lack of efficacy	1	-

Notes
[3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: FTC/RPV/TDF group: 110 participants completing the main study continued in extension phase. SBR/Delayed Switch Group: 49 participants completing the main study continued in extension phase.

Baseline characteristics

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Reporting group title

FTC/RPV/TDF

Reporting group description

Reporting group title

SBR/Delayed Switch

Reporting group description

Reporting group values	FTC/RPV/TDF	SBR/Delayed Switch	Total
Number of subjects	317	159	476
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	41 ( 9.2 )	43 ( 9.7 )	-
Gender categorical
Units: Subjects
Female	44	15	59
Male	273	144	417
Ethnicity
Units: Subjects
Hispanic or Latino	51	31	82
Not Hispanic or Latino	264	128	392
Unknown or Not Reported	2	0	2
Race
Units: Subjects
White	241	124	365
Black or African American	61	22	83
American Indian or Alaska Native	3	2	5
Asian	6	2	8
Other	6	9	15
Baseline HIV-1 RNA Category
Units: Subjects
< 50 Copies/mL	299	152	451
50 to < 200 Copies/mL	10	6	16
200 to < 400 Copies/mL	2	0	2
400 to < 1000 Copies/mL	2	0	2
≥ 1000 Copies/mL	4	1	5
Stratification based on antiretroviral (ARV) use
Units: Subjects
TDF or FTC/TDF + lopinavir (LPV)/ritonavir (RTV)	82	49	131
TDF or FTC/TDF + Other PI +RTV	178	81	259
Non-TDF-containing regimen + LPV/RTV	15	9	24
Non-TDF-containing regimen + Other PI+RTV	42	20	62

End points

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Reporting group title

FTC/RPV/TDF

Reporting group description

Reporting group title

SBR/Delayed Switch

Reporting group description

Reporting group title

FTC/RPV/TDF

Reporting group description

Reporting group title

SBR/Delayed Switch

Reporting group description

Primary: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis)

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End point title

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis)

End point description

The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the FDA snapshot analysis. Full Analysis Set: participants who were randomized into the study and received at least one dose of study drug.

End point type

Primary

End point timeframe

Week 24

End point values	FTC/RPV/TDF	SBR/Delayed Switch
Number of subjects analysed	317	159
Units: percentage of participants
number (not applicable)	93.7	89.9

HIV-1 RNA < 50 Copies/mL at Week 24

Statistical analysis description

A 95% confidence interval (CI) for the difference between treatment groups in the percentages of virologic success was constructed using normal approximation. Noninferiority was assessed using a conventional 95% CI approach, with a noninferiority margin of 12%. It would be concluded that the FTC/RPV/TDF STR group was not inferior to the SBR group if the lower bound of the 2-sided 95% CI of the difference (FTC/RPV/TDF STR – SBR) in the response rate was greater than -12%.

Comparison groups

FTC/RPV/TDF v SBR/Delayed Switch

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

Mean difference (net)

Point estimate

3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

9.1

Secondary: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis)

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End point title

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis)

End point description

The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the FDA snapshot analysis. By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF. Participants in the Full Analysis Set in the FTC/RPV/TDF and the Delayed Switch to FTC/RPV/TDF groups were analyzed.

End point type

Secondary

End point timeframe

Week 48

End point values	FTC/RPV/TDF	SBR/Delayed Switch
Number of subjects analysed	317	152
Units: percentage of participants
number (not applicable)	89.3	92.1

No statistical analyses for this end point

Secondary: Change From Baseline in Cluster of Differentiation 4 (CD4) Count Through Week 24

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End point title

Change From Baseline in Cluster of Differentiation 4 (CD4) Count Through Week 24

End point description

The mean (SD) change in CD4 count was analyzed from baseline through Week 24. Participants in the Full Analysis Set who had CD4 measurements at both baseline and Week 24 were analyzed.

End point type

Secondary

End point timeframe

Baseline to Week 24

End point values	FTC/RPV/TDF	SBR/Delayed Switch
Number of subjects analysed	298	148
Units: cells/mm^3
arithmetic mean (standard deviation)	20 ( 149.3 )	32 ( 158.1 )

No statistical analyses for this end point

Secondary: Change From Baseline in CD4 Count Through Week 48

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End point title

Change From Baseline in CD4 Count Through Week 48

End point description

The mean (SD) change in CD4 count was analyzed from baseline through Week 48. By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF. Participants in the Full Analysis Set who had CD4 measurements at both baseline and Week 48 were analyzed.

End point type

Secondary

End point timeframe

Baseline to Week 48

End point values	FTC/RPV/TDF	SBR/Delayed Switch
Number of subjects analysed	287	143
Units: cells/mm^3
arithmetic mean (standard deviation)	10 ( 144.1 )	-7 ( 154.1 )

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting Total Cholesterol Through Week 24

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End point title

Change From Baseline in Fasting Total Cholesterol Through Week 24

End point description

The mean (SD) change from baseline in fasting total cholesterol (mg/dL) through Week 24 was analyzed. Participants in the Safety Analysis Set who had measurements for total cholesterol at both baseline and Week 24 were analyzed.

End point type

Secondary

End point timeframe

Baseline to Week 24

End point values	FTC/RPV/TDF	SBR/Delayed Switch
Number of subjects analysed	269	134
Units: mg/dL
arithmetic mean (standard deviation)	-25 ( 30.2 )	-1 ( 25.9 )

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting Total Cholesterol Through Week 48

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End point title

Change From Baseline in Fasting Total Cholesterol Through Week 48

End point description

The mean (SD) change from baseline in fasting total cholesterol (mg/dL) through Week 48 was analyzed. By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF. Participants in the Safety Analysis Set who had measurements for total cholesterol at both baseline and Week 48 were analyzed.

End point type

Secondary

End point timeframe

Baseline to Week 48

End point values	FTC/RPV/TDF	SBR/Delayed Switch
Number of subjects analysed	265	139
Units: mg/dL
arithmetic mean (standard deviation)	-24 ( 32.9 )	-24 ( 32 )

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol Through Week 24

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End point title

Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol Through Week 24

End point description

The mean (SD) change from baseline in fasting HDL cholesterol (mg/dL) through Week 24 was analyzed. Participants in the Safety Analysis Set who had measurements for HDL cholesterol at both baseline and Week 24 were analyzed.

End point type

Secondary

End point timeframe

Baseline to Week 24

End point values	FTC/RPV/TDF	SBR/Delayed Switch
Number of subjects analysed	269	134
Units: mg/dL
arithmetic mean (standard deviation)	-4 ( 10.3 )	-1 ( 8.2 )

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting HDL Cholesterol Through Week 48

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End point title

Change From Baseline in Fasting HDL Cholesterol Through Week 48

End point description

The mean (SD) change from baseline in fasting HDL cholesterol (mg/dL) through Week 48 was analyzed. By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.

End point type

Secondary

End point timeframe

Baseline to Week 48

End point values	FTC/RPV/TDF	SBR/Delayed Switch
Number of subjects analysed	265	139
Units: mg/dL
arithmetic mean (standard deviation)	-2 ( 11.6 )	-2 ( 8 )

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting Direct Low-density Lipoprotein (LDL) Cholesterol Through Week 24

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End point title

Change From Baseline in Fasting Direct Low-density Lipoprotein (LDL) Cholesterol Through Week 24

End point description

The mean (SD) change from baseline in fasting direct LDL cholesterol (mg/dL) through Week 24 was analyzed. Participants in the Safety Analysis Set who had measurements for direct LDL cholesterol at both baseline and Week 24 were analyzed.

End point type

Secondary

End point timeframe

Baseline to Week 24

End point values	FTC/RPV/TDF	SBR/Delayed Switch
Number of subjects analysed	270	134
Units: mg/dL
arithmetic mean (standard deviation)	-16 ( 25.6 )	0 ( 23.7 )

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting Direct LDL Cholesterol Through Week 48

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End point title

Change From Baseline in Fasting Direct LDL Cholesterol Through Week 48

End point description

The mean (SD) change from baseline in fasting direct LDL cholesterol (mg/dL) through Week 48 was analyzed. By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF. Participants in the Safety Analysis Set who had measurements for direct LDL cholesterol at both baseline and Week 48 were analyzed.

End point type

Secondary

End point timeframe

Baseline to Week 48

End point values	FTC/RPV/TDF	SBR/Delayed Switch
Number of subjects analysed	265	139
Units: mg/dL
arithmetic mean (standard deviation)	-16 ( 27.1 )	-14 ( 26.8 )

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting Triglycerides Through Week 24

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End point title

Change From Baseline in Fasting Triglycerides Through Week 24

End point description

The mean (SD) change from baseline in fasting triglycerides through Week 24 was analyzed. Participants in the Safety Analysis Set who had measurements for triglycerides at both baseline and Week 24 were analyzed.

End point type

Secondary

End point timeframe

Baseline to Week 24

End point values	FTC/RPV/TDF	SBR/Delayed Switch
Number of subjects analysed	269	134
Units: mg/dL
arithmetic mean (standard deviation)	-53 ( 110 )	3 ( 100.1 )

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting Triglycerides Through Week 48

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End point title

Change From Baseline in Fasting Triglycerides Through Week 48

End point description

The mean (SD) change from baseline in fasting triglycerides through Week 48 was analyzed. By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF. Participants in the Safety Analysis Set who had measurements for triglycerides at both baseline and Week 48 were analyzed.

End point type

Secondary

End point timeframe

Baseline to Week 48

End point values	FTC/RPV/TDF	SBR/Delayed Switch
Number of subjects analysed	265	139
Units: mg/dL
arithmetic mean (standard deviation)	-64 ( 126.4 )	-80 ( 141.1 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline through end of study (average 54 weeks)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

FTC/RPV/TDF

Reporting group description

The adverse events reported in this group are those that occurred at any time during the study in participants who were randomized to switch from their existing treatment regimen to the FTC/RPV/TDF STR at the beginning of the study.

Reporting group title

SBR/Delayed Switch (up to Week 24)

Reporting group description

The adverse events reported in this group are those that occurred in the first 24 weeks of the study in participants who were randomized to stay on their existing treatment regimen (Stay on Baseline Regimen (SBR)) at the beginning of the study and switch to the FTC/RPV/TDF STR (Delayed Switch) at the Week 24 visit.

Reporting group title

SBR/Delayed Switch (After Week 24)

Reporting group description

The adverse events reported in this group are those that occurred after Week 24 in participants who were randomized to stay on their existing treatment regimen (Stay on Baseline Regimen (SBR)) at the beginning of the study and switch to the FTC/RPV/TDF STR (Delayed Switch) at Week 24 visit.

Serious adverse events	FTC/RPV/TDF	SBR/Delayed Switch (up to Week 24)	SBR/Delayed Switch (After Week 24)
Total subjects affected by serious adverse events
subjects affected / exposed	21 / 317 (6.62%)	8 / 159 (5.03%)	9 / 152 (5.92%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of thyroid gland
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Arterial occlusive disease
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 317 (0.32%)	1 / 159 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Prostatism
subjects affected / exposed	0 / 317 (0.00%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sleep apnoea syndrome
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bipolar disorder
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Substance-induced mood disorder
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 317 (0.00%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Procedural pain
subjects affected / exposed	0 / 317 (0.00%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Stab wound
subjects affected / exposed	0 / 317 (0.00%)	1 / 159 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina unstable
subjects affected / exposed	0 / 317 (0.00%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Palpitations
subjects affected / exposed	0 / 317 (0.00%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Hypoaesthesia
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sensory loss
subjects affected / exposed	0 / 317 (0.00%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neuropathy peripheral
subjects affected / exposed	0 / 317 (0.00%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Visual acuity reduced
subjects affected / exposed	0 / 317 (0.00%)	1 / 159 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 317 (0.00%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephropathy toxic
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal impairment
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthritis reactive
subjects affected / exposed	0 / 317 (0.00%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bursitis
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal chest pain
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Polyarthritis
subjects affected / exposed	0 / 317 (0.00%)	1 / 159 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	3 / 317 (0.95%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute sinusitis
subjects affected / exposed	0 / 317 (0.00%)	1 / 159 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 317 (0.00%)	1 / 159 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lung infection
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Parainfluenzae virus infection
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Shigella infection
subjects affected / exposed	0 / 317 (0.00%)	1 / 159 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 317 (0.00%)	0 / 159 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 317 (0.00%)	1 / 159 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	1 / 317 (0.32%)	0 / 159 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 317 (0.00%)	1 / 159 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	FTC/RPV/TDF	SBR/Delayed Switch (up to Week 24)	SBR/Delayed Switch (After Week 24)
Total subjects affected by non serious adverse events
subjects affected / exposed	150 / 317 (47.32%)	38 / 159 (23.90%)	59 / 152 (38.82%)
Nervous system disorders
Headache
subjects affected / exposed	31 / 317 (9.78%)	6 / 159 (3.77%)	6 / 152 (3.95%)
occurrences all number	37	6	8
General disorders and administration site conditions
Fatigue
subjects affected / exposed	22 / 317 (6.94%)	5 / 159 (3.14%)	4 / 152 (2.63%)
occurrences all number	22	5	4
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	34 / 317 (10.73%)	8 / 159 (5.03%)	6 / 152 (3.95%)
occurrences all number	37	8	7
Nausea
subjects affected / exposed	13 / 317 (4.10%)	5 / 159 (3.14%)	10 / 152 (6.58%)
occurrences all number	13	5	10
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	23 / 317 (7.26%)	1 / 159 (0.63%)	2 / 152 (1.32%)
occurrences all number	23	1	2
Psychiatric disorders
Insomnia
subjects affected / exposed	21 / 317 (6.62%)	3 / 159 (1.89%)	9 / 152 (5.92%)
occurrences all number	21	3	9
Depression
subjects affected / exposed	18 / 317 (5.68%)	4 / 159 (2.52%)	6 / 152 (3.95%)
occurrences all number	18	4	6
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	13 / 317 (4.10%)	6 / 159 (3.77%)	8 / 152 (5.26%)
occurrences all number	16	6	8
Arthralgia
subjects affected / exposed	18 / 317 (5.68%)	2 / 159 (1.26%)	3 / 152 (1.97%)
occurrences all number	19	2	3
Infections and infestations
Nasopharyngitis
subjects affected / exposed	35 / 317 (11.04%)	8 / 159 (5.03%)	12 / 152 (7.89%)
occurrences all number	44	10	13
Upper respiratory tract infection
subjects affected / exposed	15 / 317 (4.73%)	5 / 159 (3.14%)	13 / 152 (8.55%)
occurrences all number	15	5	18

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

There were no limitations affecting the analysis or results.

http://www.ncbi.nlm.nih.gov/pubmed/2467052

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis)

Primary: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis)

Secondary: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis)

Secondary: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis)

Secondary: Change From Baseline in Cluster of Differentiation 4 (CD4) Count Through Week 24

Secondary: Change From Baseline in Cluster of Differentiation 4 (CD4) Count Through Week 24

Secondary: Change From Baseline in CD4 Count Through Week 48

Secondary: Change From Baseline in CD4 Count Through Week 48

Secondary: Change From Baseline in Fasting Total Cholesterol Through Week 24

Secondary: Change From Baseline in Fasting Total Cholesterol Through Week 24

Secondary: Change From Baseline in Fasting Total Cholesterol Through Week 48

Secondary: Change From Baseline in Fasting Total Cholesterol Through Week 48

Secondary: Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol Through Week 24

Secondary: Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol Through Week 24

Secondary: Change From Baseline in Fasting HDL Cholesterol Through Week 48

Secondary: Change From Baseline in Fasting HDL Cholesterol Through Week 48

Secondary: Change From Baseline in Fasting Direct Low-density Lipoprotein (LDL) Cholesterol Through Week 24

Secondary: Change From Baseline in Fasting Direct Low-density Lipoprotein (LDL) Cholesterol Through Week 24

Secondary: Change From Baseline in Fasting Direct LDL Cholesterol Through Week 48

Secondary: Change From Baseline in Fasting Direct LDL Cholesterol Through Week 48

Secondary: Change From Baseline in Fasting Triglycerides Through Week 24

Secondary: Change From Baseline in Fasting Triglycerides Through Week 24

Secondary: Change From Baseline in Fasting Triglycerides Through Week 48

Secondary: Change From Baseline in Fasting Triglycerides Through Week 48

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

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