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Clinical Trial Results:
A Phase III, randomized, multicenter, parallel-group, non inferiority study evaluating the efficacy, safety, and tolerability of switching to dolutegravir plus rilpivirine from current INSTI-, NNRTI-, or PI-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed

Summary
EudraCT number	2014-005148-16
Trial protocol	ES DE GB FR IT
Global end of trial date

Results information
Results version number	v6(current)
This version publication date	06 Nov 2020
First version publication date	12 Aug 2017
Other versions	v1 , v2 , v3 , v4 , v5
Version creation reason	New data added to full data set Include summary for sub study of 202094
Summary report(s)	202094 study results - Sub study of 201636 and 201637 studies (EudraCT #2014-005147-40 &#2014-005148-16)

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

201637

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

ViiV Healthcare

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

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

Interim

Date of interim/final analysis

20 Feb 2017

Is this the analysis of the primary completion data?

Yes

Primary completion date

16 Sep 2016

Global end of trial reached?

Main objective of the trial

To demonstrate the non-inferior antiviral activity of switching to dolutegravir (DTG) plus rilpivirine (RPV) once daily compared to continuation of current antiretroviral regimen (CAR) over 48 weeks in HIV-1 infected antiretroviral therapy (ART)-experienced virologically suppressed subjects.

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

21 Apr 2015

Long term follow-up planned

Yes

Long term follow-up rationale

Scientific research

Long term follow-up duration

4 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 245

Country: Number of subjects enrolled

Taiwan: 17

Country: Number of subjects enrolled

United Kingdom: 4

Country: Number of subjects enrolled

United States: 40

Country: Number of subjects enrolled

Argentina: 24

Country: Number of subjects enrolled

Australia: 34

Country: Number of subjects enrolled

Canada: 37

Country: Number of subjects enrolled

France: 30

Country: Number of subjects enrolled

Germany: 39

Country: Number of subjects enrolled

Italy: 18

Country: Number of subjects enrolled

Russian Federation: 30

Worldwide total number of subjects

518

EEA total number of subjects

336

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)

507

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study was a 148-week, Phase III, randomized, open-label, active-controlled, multicenter, parallel-group, non-inferiority study to assess the antiviral activity and safety of a two-drug regimen of dolutegravir (DTG) + rilpivirine (RPV) compared with current antiretroviral regimen (CAR). The study was conducted at 60 centers in 11 countries.

Screening details

Total 639 participants were screened (121 failed), 518 participants were randomized and 2 participants withdrew before being exposed to study drug. The study included a Screening phase, an early switch phase, a late switch phase, and a continuation phase. The results presented are based on the interim analysis of the Late Switch Phase (Week 148).

Period 1 title

Early Switch Phase (Up to Week 52)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

DTG + RPV

Arm description

Participants received DTG 50 milligrams (mg) + RPV 25 mg together once daily at approximately the same time, with a meal, in an open-label fashion up to Week 52 during early switch phase. Participants continued to receive DTG 50 mg + RPV 25 mg up to Week 148 during the Late Switch Phase.

Arm type

Experimental

Investigational medicinal product name

Rilpivirine Tablets 25 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received rilpivirine tablets 25 mg once daily, with a meal, in an open-label fashion up to Week 52 during early switch phase.

Investigational medicinal product name

Dolutegravir Tablets 50 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received dolutegravir tablets 50 mg once daily, with a meal, in an open-label fashion up to Week 52 during early switch phase

Current antiretroviral regimen

Arm description

Participants continued to receive their current antiretroviral regimen (two nucleoside reverse transcriptase inhibitor [NRTIs] + a third agent). A third agent included either an: integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). CAR was administered according to the approved labeling in an open-label fashion up to Week 52 during early switch phase. At Week 52, participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) <50 copies per milliliter (c/mL), switched to DTG 50 mg + RPV 25 mg once daily and were followed until Week 148.

Arm type

Active comparator

Investigational medicinal product name

Current antiretroviral regimen (not IMP)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received their current antiretroviral regimen (2 NRTIs + a third agent). A third agent included either of INSTI, NNRTI, or PI. CAR was administered according to the approved labeling in an open-label fashion up to Week 52 during early switch phase.

Number of subjects in period 1 ^[1]	DTG + RPV	Current antiretroviral regimen
Started	261	255
Completed	245	239
Not completed	16	16
Consent withdrawn by subject	2	7
Physician decision	-	1
Adverse event, non-fatal	11	1
Reached stopping criteria	1	1
Lost to follow-up	1	1
Lack of efficacy	1	2
Protocol deviation	-	3

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: Total 518 participants were randomized, of which 2 participants withdrew before being exposed to study drug.

Period 2 title

Late Switch Phase (Week 52 to Week 148)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

DTG + RPV

Arm description

Arm type

Experimental

Investigational medicinal product name

Rilpivirine Tablets 25 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received rilpivirine tablets 25 mg once daily, with a meal, in an open-label fashion from Week 52 to Week 148 during late Switch phase.

Investigational medicinal product name

Dolutegravir Tablets 50 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received dolutegravir tablets 50 mg once daily, with a meal, in an open-label fashion from Week 52 to Week 148 during late switch phase.

Current antiretroviral regimen

Arm description

Arm type

Active comparator

Investigational medicinal product name

Rilpivirine Tablets 25 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received rilpivirine tablets 25 mg once daily, with a meal, in an open-label fashion from Week 52 to Week 148 during late Switch phase.

Investigational medicinal product name

Dolutegravir Tablets 50 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received dolutegravir tablets 50 mg once daily, with a meal, in an open-label fashion from Week 52 to Week 148 during late switch phase.

Number of subjects in period 2	DTG + RPV	Current antiretroviral regimen
Started	245	239
Completed	222	221
Not completed	23	18
Consent withdrawn by subject	2	6
Physician decision	-	1
Adverse event, non-fatal	10	6
Reached stopping criteria	1	-
Lost to follow-up	2	2
Lack of efficacy	5	3
Protocol deviation	3	-

Baseline characteristics

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Reporting group title

DTG + RPV

Reporting group description

Reporting group title

Current antiretroviral regimen

Reporting group description

Reporting group values	DTG + RPV	Current antiretroviral regimen	Total
Number of subjects	261	255	516
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	253	252	505
From 65-84 years	8	3	11
85 years and over	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	43.3 ( 11.34 )	43.2 ( 9.64 )	-
Sex: Female, Male
Units: Subjects
Female	62	57	119
Male	199	198	397
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	11	7	18
Central/South Asian Heritage	0	1	1
Japanese/East Asian (EA) Heritage (H.)/South EA H.	13	15	28
Black/African American	13	19	32
Native Hawaiian or other Pacific Islander	1	0	1
White	223	212	435
African American/ African H. and White	0	1	1

End points

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Reporting group title

DTG + RPV

Reporting group description

Reporting group title

Current antiretroviral regimen

Reporting group description

Reporting group title

DTG + RPV

Reporting group description

Reporting group title

Current antiretroviral regimen

Reporting group description

Subject analysis set title

DTG 50 mg PK Parameter Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received DTG 50 mg + RPV 25 mg together once daily, with a meal, in an open-label fashion up to Week 148 during early switch and late switch phase. The arm is specific for participants in the PK Parameter Population.

Subject analysis set title

RPV 25 mg PK Parameter Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received DTG 50 mg +RPV 25 mg together once daily, with a meal, in an open-label fashion up to Week 148 during early switch and late switch phase. The arm is specific for participants in the PK Parameter Population.

Subject analysis set title

CAR-DTG 50 mg LS PK Parameter Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants from CAR arm received DTG 50 mg + RPV 25 mg together once daily, with a meal, in an open-label fashion from Week 52 to Week 148 during late switch phase. The arm is specific for participants in LS PK Parameter Population.

Subject analysis set title

CAR-RPV 25mg LS PK Parameter Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants from CAR arm received DTG 50 mg +RPV 25 mg together once daily, with a meal, in an open-label fashion from Week 52 to Week 148 during late switch phase. The arm is specific for participants in LS PK Parameter Population.

Subject analysis set title

DTG 50 mg PK Parameter NNRTI Subset

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received DTG 50 mg + RPV 25 mg together once daily, with a meal, in an open-label fashion up to Week 52 during early switch phase. The arm is specific for participants in PK Parameter NNRTI Subset extra sampling Population.

Subject analysis set title

RPV 25 mg PK Parameter NNRTI Subset

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received DTG 50 mg +RPV 25 mg together once daily, with a meal, in an open-label fashion up to Week 52 during early switch phase. The arm is specific for participants in PK Parameter NNRTI Subset extra sampling Population.

Primary: Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using snapshot algorithm

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End point title

Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using snapshot algorithm

End point description

Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 48 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to demonstrate the non-inferior antiviral activity of switching to DTG+RPV once daily compared to continuation of CAR over 48 weeks in HIV-1 infected antiretroviral therapy (ART)-experienced participants. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest. Plasma samples were collected for quantitative analysis of HIV-1 RNA. The Intent-to-Treat Exposed (ITT-E) population consisted of all randomly assigned participants who received at least one dose of study drug.

End point type

Primary

End point timeframe

Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[1]	255 ^[2]
Units: Percentage of participants
number (not applicable)	94	94

Notes
[1] - ITT-E Population
[2] - ITT-E Population

Statistical Analysis 1

Statistical analysis description

Estimates based on Cochran-Mantel Haenszel stratified analysis adjusting for Baseline stratification factors: Age group (< or >=50 years old) and Baseline third agent (PI, NNRTI, INSTI).

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

^[3]

Method

Parameter type

Risk difference (RD)

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-3.9

upper limit

4.2

Notes
[3] - Non-inferiority can be concluded if the lower bound of a two-sided 95% confidence interval for the difference in response rates between the two treatment arms is greater than -10%.

Secondary: Changes from Baseline in cluster designation (CD)4+ lymphocyte count at Weeks 24 and 48

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End point title

Changes from Baseline in cluster designation (CD)4+ lymphocyte count at Weeks 24 and 48

End point description

Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunological activity of DTG + RPV once daily compared to continuation of CAR. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1), Weeks 24 and 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[4]	255 ^[5]
Units: Cells per millimeter cube (mm^3)
arithmetic mean (standard deviation)
Week 24, n=251, 250	42.0 ( 172.29 )	42.4 ( 164.85 )
Week 48, n=245, 241	28.0 ( 169.35 )	18.4 ( 159.34 )

Notes
[4] - ITT-E Population
[5] - ITT-E Population

No statistical analyses for this end point

Secondary: Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 24 using snapshot algorithm

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End point title

Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 24 using snapshot algorithm

End point description

Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 24 using the FDA snapshot algorithm was assessed to evaluate the antiviral activity of DTG +RPV once daily compared to continuation of CAR. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest. Plasma samples were collected for quantitative analysis of HIV-1 RNA.

End point type

Secondary

End point timeframe

Week 24

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[6]	255 ^[7]
Units: Percentage of participants
number (not applicable)	97	98

Notes
[6] - ITT-E Population
[7] - ITT-E Population

Statistical Analysis 1

Statistical analysis description

Cochran-Mantel Haenszel stratified analysis adjusting for Baseline stratification factors: Age group (< or >=50 years old) and Baseline third agent (PI, NNRTI, INSTI). No formal non-inferiority margin has been pre-specified for secondary endpoints.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Risk difference (RD)

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

1.8

Secondary: Number of participants with common non-serious adverse event (AE), any serious AE (SAE), AE of maximum toxicity grade 1, 2, 3 or 4 and AE leading to discontinuation (AELD)

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End point title

Number of participants with common non-serious adverse event (AE), any serious AE (SAE), AE of maximum toxicity grade 1, 2, 3 or 4 and AE leading to discontinuation (AELD)

End point description

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a medicinal product, whether or not considered related to medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention were categorized as SAE. AEs were graded using the Division of Acquired Immunodeficiency Syndrome (AIDS) grading. Grade 1=mild; Grade 2=moderate, Grade 3=severe and Grade 4=potentially life-threatening. Common AEs were those with >5% incidence for either treatment. This summary presents results as reported after all participants completed the Early Switch Phase.

End point type

Secondary

End point timeframe

Up to Week 52

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[8]	255 ^[9]
Units: Participants
Common non-serious AE	61	59
Any SAE	18	9
Maximum toxicity Grade 1 AE	119	122
Maximum toxicity Grade 2 AE	59	47
Maximum toxicity Grade 3 AE	16	4
Maximum toxicity Grade 4 AE	1	1
AELD	12	1

Notes
[8] - Safety Population included all randomized participants who received at least one dose of study drug
[9] - Safety Population included all randomized participants who received at least one dose of study drug

No statistical analyses for this end point

Secondary: Number of participants with maximum post-baseline emergent chemistry toxicities over 48 weeks

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End point title

Number of participants with maximum post-baseline emergent chemistry toxicities over 48 weeks

End point description

Blood samples were collected to evaluate alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin, chloride, creatinine, glucose, potassium, phosphate, sodium, blood urea nitrogen (BUN), total carbon dioxide, lipase, creatine phosphokinase and creatinine clearance. Value obtained at Day 1 was considered as Baseline value. Number of participants who experienced maximum grade toxicity post-baseline in clinical chemistry over 48 weeks was summarized. Clinical chemistry toxicities were graded using the Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events. Grade 1=mild; Grade 2=moderate, Grade 3=severe and Grade 4=potentially life-threatening. For all laboratory parameters, one assessment out of range was sufficient to be considered a chemistry toxicity.

End point type

Secondary

End point timeframe

Up to 48 weeks

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[10]	255 ^[11]
Units: Participants
Grade 1	92	80
Grade 2	72	79
Grade 3	11	16
Grade 4	1	10

Notes
[10] - Safety Population
[11] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with maximum post-baseline emergent hematology toxicities over 48 weeks

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End point title

Number of participants with maximum post-baseline emergent hematology toxicities over 48 weeks

End point description

Blood samples were collected to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, mean corpuscular volume (MCV), red blood cell (RBC) count, white blood cell (WBC) count and platelet count. Value obtained at Day 1 was considered as Baseline value. Number of participants who experienced maximum grade toxicity post-baseline in hematology over 48 weeks was summarized. Participants were graded using the Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events. Grade 1=mild; Grade 2=moderate, Grade 3=severe and Grade 4=potentially life-threatening. For all laboratory parameters, one assessment out of range was sufficient to be considered a hematology toxicity.

End point type

Secondary

End point timeframe

Up to 48 weeks

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[12]	255 ^[13]
Units: Participants
Grade 1	11	11
Grade 2	2	2
Grade 3	3	0
Grade 4	1	0

Notes
[12] - Safety Population
[13] - Safety Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in high-sensitivity C-reactive protein (hs-CRP) at Week 48

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End point title

Mean change from Baseline in high-sensitivity C-reactive protein (hs-CRP) at Week 48

End point description

Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess hs-CRP. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	246 ^[14]	239 ^[15]
Units: mg/Liter (L)
arithmetic mean (standard deviation)	0.10 ( 5.383 )	0.80 ( 8.527 )

Notes
[14] - Safety Population
[15] - Safety Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in cystatin C at Week 48

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End point title

Mean change from Baseline in cystatin C at Week 48

End point description

Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess cystatin C. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	246 ^[16]	237 ^[17]
Units: mg/L
arithmetic mean (standard deviation)	-0.02 ( 0.110 )	-0.01 ( 0.108 )

Notes
[16] - Safety Population
[17] - Safety Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in D-Dimer at Week 48

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End point title

Mean change from Baseline in D-Dimer at Week 48

End point description

Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess D-Dimer. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	239 ^[18]	228 ^[19]
Units: Nanomole/L fibrinogen equivalent units
arithmetic mean (standard deviation)	0.01 ( 1.629 )	-0.13 ( 2.932 )

Notes
[18] - Safety Population
[19] - Safety Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in fatty acid binding protein 2 (FABP) and soluble CD14 at Week 48

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End point title

Mean change from Baseline in fatty acid binding protein 2 (FABP) and soluble CD14 at Week 48

End point description

Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess FABP and soluble CD14. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[20]	255 ^[21]
Units: Nanogram/milliliter
arithmetic mean (standard deviation)
FABP, n=245, 236	-1.50 ( 1.278 )	-0.99 ( 1.441 )
Soluble CD14, n=245, 237	456.69 ( 731.833 )	802.26 ( 878.304 )

Notes
[20] - Safety Population
[21] - Safety Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in Soluble CD163 and oxidized low density lipoprotein (LDL) at Week 48

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End point title

Mean change from Baseline in Soluble CD163 and oxidized low density lipoprotein (LDL) at Week 48

End point description

Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess soluble CD163 and oxidized LDL. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[22]	255 ^[23]
Units: Microgram/Liter
arithmetic mean (standard deviation)
Soluble CD163, n=245, 236	65.38 ( 180.869 )	53.94 ( 215.621 )
Oxidized LDL, n=245, 237	60.87 ( 504.345 )	13.92 ( 575.305 )

Notes
[22] - Safety Population
[23] - Safety Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in retinol binding protein (RBP), serum creatinine and glucose at Week 48

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End point title

Mean change from Baseline in retinol binding protein (RBP), serum creatinine and glucose at Week 48

End point description

Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess RBP, serum creatinine and glucose. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[24]	255 ^[25]
Units: mg/deciliter (dL)
arithmetic mean (standard deviation)
RBP, n=245, 237	-0.13 ( 0.825 )	0.00 ( 0.872 )
Serum creatinine, n=245, 241	0.100 ( 0.1053 )	-0.003 ( 0.0847 )
Glucose, n=242, 235	0.187 ( 19.5808 )	3.220 ( 10.0987 )

Notes
[24] - Safety Population
[25] - Safety Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in urine phosphate at Week 48

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End point title

Mean change from Baseline in urine phosphate at Week 48

End point description

Urine biomarker samples were collected to at Baseline (Day 1) and Week 48 to assess urine phosphate. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	235 ^[26]	229 ^[27]
Units: Millimoles (mmol)/ L
arithmetic mean (standard deviation)	1.335 ( 16.7211 )	-0.798 ( 15.3771 )

Notes
[26] - Safety Population
[27] - Safety Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in beta-2-microglobulin (B2M) (blood and urine), urine RBP and 25 hydroxy-vitamin D (blood) at Week 48

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End point title

Mean change from Baseline in beta-2-microglobulin (B2M) (blood and urine), urine RBP and 25 hydroxy-vitamin D (blood) at Week 48

End point description

Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess B2M and 25 hydroxy-vitamin D. Urine biomarker samples were collected to assess B2M and RBP. Change from Baseline was calculated as value at indicated time point minus Baseline value. For 25 hydroxy-vitamin D, analysis of changes from Baseline was performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[28]	255 ^[29]
Units: Nanomoles (nmol)/L
arithmetic mean (standard deviation)
B2M, blood, n=245, 238	-16.8800 ( 34.89330 )	-4.7501 ( 43.04355 )
25 hydroxy-vitamin D, blood, n=243, 239	-13.9 ( 25.30 )	-9.2 ( 19.55 )
Urine B2M, n=72, 78	-173.2820 ( 1311.24142 )	62.3209 ( 391.32049 )
Urine RBP, n=232, 224	-6.8123 ( 24.09650 )	-0.0631 ( 11.99886 )

Notes
[28] - Safety Population
[29] - Safety Population

Statistical Analysis 1

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.007 ^[30]

Method

ANCOVA

Confidence interval

Notes
[30] - P-value for interaction between treatment group and Baseline third agent (25 hydroxy-vitamin D)

Statistical Analysis 2

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.011 ^[31]

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.861

Confidence interval

level

95%

sides

2-sided

lower limit

0.767

upper limit

0.967

Notes
[31] - P value to assess difference between treatment groups (25 hydroxy-vitamin D - INSTI)

Statistical Analysis 3

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.745 ^[32]

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

1.012

Confidence interval

level

95%

sides

2-sided

lower limit

0.943

upper limit

1.085

Notes
[32] - P value to assess difference between treatment groups (25 hydroxy-vitamin D - NNRTI)

Statistical Analysis 4

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.018 ^[33]

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.877

Confidence interval

level

95%

sides

2-sided

lower limit

0.787

upper limit

0.977

Notes
[33] - P value to assess difference between treatment groups (25 hydroxy-vitamin D - PI)

Secondary: Mean change from Baseline in urine albumin/creatinine ratio and urine protein/creatinine ratio at Week 48

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End point title

Mean change from Baseline in urine albumin/creatinine ratio and urine protein/creatinine ratio at Week 48

End point description

Urine biomarker samples were collected at Baseline (Day 1) and Week 48 to assess urine albumin/creatinine ratio and urine protein/creatinine ratio. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[34]	255 ^[35]
Units: Grams (g)/ mol
arithmetic mean (standard deviation)
Urine albumin/creatinine ratio, n=178, 181	-0.78 ( 5.116 )	-0.64 ( 9.538 )
Urine protein/creatinine ratio, n=192, 193	-2.73 ( 12.683 )	1.23 ( 5.088 )

Notes
[34] - Safety Population
[35] - Safety Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in bone-specific alkaline phosphatase, procollagen 1 N-terminal propeptide, osteocalcin, Type 1 Collagen C-telopeptides and soluble vascular cell adhesion molecule (sVCAM) at Week 48

Top of page

End point title

Mean change from Baseline in bone-specific alkaline phosphatase, procollagen 1 N-terminal propeptide, osteocalcin, Type 1 Collagen C-telopeptides and soluble vascular cell adhesion molecule (sVCAM) at Week 48

End point description

Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess bone-specific alkaline phosphatase, procollagen 1 N-terminal propeptide, osteocalcin, Type 1 Collagen C-telopeptides and sVCAM. Change from Baseline was calculated as value at indicated time point minus Baseline value. For bone-specific alkaline phosphatase, procollagen 1-N-propeptide, osteocalcin and type 1 collagen C-telopeptide, analyses of changes from Baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[36]	255 ^[37]
Units: Microgram (ug)/ L
arithmetic mean (standard deviation)
Bone-specific alkaline phosphatase, n=246, 236	-3.18 ( 5.678 )	0.92 ( 4.634 )
Procollagen type 1 N-propeptide, n=245, 237	-5.8 ( 20.00 )	0.3 ( 19.28 )
Osteocalcin, n=245, 235	-5.11 ( 7.334 )	-1.14 ( 6.017 )
Type I Collagen C-Telopeptides, n=243, 238	-0.15 ( 0.313 )	-0.09 ( 0.344 )
sVCAM, n=245, 237	-2.63 ( 571.182 )	37.42 ( 617.486 )

Notes
[36] - Safety Population
[37] - Safety Population

Statistical Analysis 1

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.001 ^[38]

Method

ANCOVA

Confidence interval

Notes
[38] - P-value for interaction between treatment group and Baseline third agent (bone-specific alkaline phosphatase)

Statistical Analysis 2

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[39]

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.728

Confidence interval

level

95%

sides

2-sided

lower limit

0.686

upper limit

0.773

Notes
[39] - P value to assess difference between treatment groups (bone-specific alkaline phosphatase - NNRTI)

Statistical Analysis 3

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.004 ^[40]

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.865

Confidence interval

level

95%

sides

2-sided

lower limit

0.785

upper limit

0.954

Notes
[40] - P value to assess difference between treatment groups (bone-specific alkaline phosphatase - INSTI)

Statistical Analysis 4

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[41]

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.788

Confidence interval

level

95%

sides

2-sided

lower limit

0.719

upper limit

0.864

Notes
[41] - P value to assess difference between treatment groups (bone-specific alkaline phosphatase - PI)

Statistical Analysis 5

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.677 ^[42]

Method

ANCOVA

Confidence interval

Notes
[42] - P-value for interaction between treatment group and Baseline third agent (procollagen type 1-N-propeptide)

Statistical Analysis 6

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[43]

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.867

Confidence interval

level

95%

sides

2-sided

lower limit

0.823

upper limit

0.914

Notes
[43] - P value to assess difference between treatment groups (procollagen type 1-N-propeptide)

Statistical Analysis 7

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[44]

Method

ANCOVA

Confidence interval

Notes
[44] - P-value for interaction between treatment group and Baseline third agent (osteocalcin)

Statistical Analysis 8

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[45]

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.853

Confidence interval

level

95%

sides

2-sided

lower limit

0.799

upper limit

0.91

Notes
[45] - P value to assess difference between treatment groups (osteocalcin - NNRTI)

Statistical Analysis 9

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.028 ^[46]

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.886

Confidence interval

level

95%

sides

2-sided

lower limit

0.796

upper limit

0.987

Notes
[46] - P value to assess difference between treatment groups (osteocalcin - INSTI)

Statistical Analysis 10

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[47]

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.743

Confidence interval

level

95%

sides

2-sided

lower limit

0.672

upper limit

0.822

Notes
[47] - P value to assess difference between treatment groups (osteocalcin - PI)

Statistical Analysis 11

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.782 ^[48]

Method

ANCOVA

Confidence interval

Notes
[48] - P-value for interaction between treatment group and Baseline third agent (type 1 collagen cross-linked C-telopeptide)

Statistical Analysis 12

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[49]

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.818

Confidence interval

level

95%

sides

2-sided

lower limit

0.751

upper limit

0.891

Notes
[49] - P value to assess difference between treatment groups (type 1 collagen cross-linked C-telopeptide)

Secondary: Mean change from Baseline in interleukin 6 (IL-6) at Week 48

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End point title

Mean change from Baseline in interleukin 6 (IL-6) at Week 48

End point description

Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess IL-6. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	245 ^[50]	237 ^[51]
Units: Nanograms (ng)/L
arithmetic mean (standard deviation)	-0.08 ( 2.373 )	-0.07 ( 2.761 )

Notes
[50] - Safety Population
[51] - Safety Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in insulin resistance based on homeostasis model assessment of insulin resistance (HOMA-IR) at Week 48

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End point title

Mean change from Baseline in insulin resistance based on homeostasis model assessment of insulin resistance (HOMA-IR) at Week 48

End point description

Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess insulin resistance. Change from Baseline was calculated as value at indicated time point minus Baseline value. The homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR ) index , the product of basal glucose and insulin levels divided by 22.5, is regarded as a simple, inexpensive, and reliable surrogate measure of insulin resistance. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	237 ^[52]	224 ^[53]
Units: HOMA-IR Score
arithmetic mean (standard deviation)	0.50 ( 4.780 )	0.80 ( 3.938 )

Notes
[52] - Safety Population
[53] - Safety Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in fasting lipids at Weeks 24 and 48

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End point title

Mean change from Baseline in fasting lipids at Weeks 24 and 48

End point description

Blood samples were collected at Baseline (Day 1), Week 24 and Week 48 to assess fasting lipids which included total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1), Weeks 24 and 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[54]	255 ^[55]
Units: Millimoles (mmol)/ L
arithmetic mean (standard deviation)
Total cholesterol, Week 24, n=237, 229	-0.015 ( 0.7539 )	0.020 ( 0.5777 )
Total cholesterol, Week 48, n=237, 230	-0.079 ( 0.7926 )	-0.038 ( 0.6148 )
LDL cholesterol calculation, Week 24, n=231, 221	0.085 ( 0.5940 )	0.055 ( 0.5232 )
LDL cholesterol calculation, Week 48, n=229, 220	-0.049 ( 0.6276 )	-0.076 ( 0.5280 )
HDL cholesterol direct, Week 24, n=237, 229	-0.024 ( 0.2365 )	-0.051 ( 0.2258 )
HDL cholesterol direct, Week 48, n=237, 230	0.051 ( 0.2386 )	0.049 ( 0.2489 )
Triglycerides, Week 24, n=237, 229	-0.184 ( 1.0102 )	0.040 ( 0.9164 )
Triglycerides, Week 48, n=237, 230	-0.169 ( 1.0062 )	-0.021 ( 1.0156 )

Notes
[54] - Safety Population
[55] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with genotypic resistance-Early switch Phase

Top of page

End point title

Number of participants with genotypic resistance-Early switch Phase

End point description

Plasma samples were collected for drug resistance testing. Genotypic Resistance data for the following drugs (Rilpivirine [RPV], Dolutegravir [DTG]) in participants Meeting Confirmed Virologic Withdrawal (CVW) criteria has been presented. CVW resistance Population comprised of all participants in the ITT-E Population who met CVW through the end of visit window (Week 48, Week 100 or Week 148) and have available on-treatment genotypic resistance data at the time CVW criterion is met.

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	1 ^[56]	0 ^[57]
Units: Participants
INSTI, DTG, Susceptible	1
INSTI, DTG, Potential low-level resistance	0
INSTI, DTG, Low-level resistance	0
INSTI, DTG, Intermediate resistance	0
INSTI, DTG, High-level resistance	0
NNRTI, RPV, Susceptible	0
NNRTI, RPV, Potential low-level resistance	0
NNRTI, RPV, Low-level resistance	0
NNRTI, RPV, Intermediate resistance	1
NNRTI, RPV, High-level resistance	0

Notes
[56] - CVW resistance Population
[57] - CVW resistance Population

No statistical analyses for this end point

Secondary: Number of participants with genotypic resistance-DTG+RPV early switch group through Early and Late Switch Phase

Top of page

End point title

Number of participants with genotypic resistance-DTG+RPV early switch group through Early and Late Switch Phase ^[58]

End point description

Plasma samples were collected for drug resistance testing. Genotypic Resistance data for the following drugs (DTG, Elvitegravir [EVG], Raltegravir [RAL], Delavirdine [DLV], Efavirenz [EFV], Etravirine [ETR], Nevirapine [NVP], RPV, Lamivudine [3TC], Abacavir [ABC], FTC, TDF, Zidovudine [ZDV], Stavudine [d4T], Didanosine [ddI], Atazanavir/r [ATV/r], DRV/r, Fosamprenavir/r [FPV/r], Indinavir/r [IDV/r], Lopinavir/r [LPV/r], Nelfinavir [NFV], Ritonavir [RTV], Saquinavir/r [SQV/r], Tipranavir/r [TPV/r]) in participants Meeting Confirmed Virologic Withdrawal Criteria has been presented.

End point type

Secondary

End point timeframe

Up to Week 148

Notes
[58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were performed.

End point values	DTG + RPV
Number of subjects analysed	2 ^[59]
Units: Participants
INI, DTG, Susceptible	2
INI, DTG, Potential low-level resistance	0
INI, DTG, Low-level resistance	0
INI, DTG, Intermediate resistance	0
INI, DTG, High-level resistance	0
INI, EVG, Susceptible	2
INI, EVG, Potential low-level resistance	0
INI, EVG, Low-level resistance	0
INI, EVG, Intermediate resistance	0
INI, EVG, High-level resistance	0
INI, RAL, Susceptible	2
INI, RAL, Potential low-level resistance	0
INI, RAL, Low-level resistance	0
INI, RAL, Intermediate resistance	0
INI, RAL, High-level resistance	0
NNRTI, DLV, Susceptible	2
NNRTI, DLV, Potential low-level resistance	0
NNRTI, DLV, Low-level resistance	0
NNRTI, DLV, Intermediate resistance	0
NNRTI, DLV, High-level resistance	0
NNRTI, EFV, Susceptible	0
NNRTI, EFV, Potential low-level resistance	0
NNRTI, EFV, Low-level resistance	1
NNRTI, EFV, Intermediate resistance	0
NNRTI, EFV, High-level resistance	1
NNRTI, ETR, Susceptible	0
NNRTI, ETR, Potential low-level resistance	0
NNRTI, ETR, Low-level resistance	1
NNRTI, ETR, Intermediate resistance	0
NNRTI, ETR, High-level resistance	1
NNRTI, NVP, Susceptible	0
NNRTI, NVP, Potential low-level resistance	0
NNRTI, NVP, Low-level resistance	0
NNRTI, NVP, Intermediate resistance	1
NNRTI, NVP, High-level resistance	1
NNRTI, RPV, Susceptible	0
NNRTI, RPV, Potential low-level resistance	0
NNRTI, RPV, Low-level resistance	0
NNRTI, RPV, Intermediate resistance	1
NNRTI, RPV, High-level resistance	1
NRTI, 3TC, Susceptible	2
NRTI, 3TC, Potential low-level resistance	0
NRTI, 3TC, Low-level resistance	0
NRTI, 3TC, Intermediate resistance	0
NRTI, 3TC, High-level resistance	0
NRTI, ABC, Susceptible	2
NRTI, ABC, Potential low-level resistance	0
NRTI, ABC, Low-level resistance	0
NRTI, ABC, Intermediate resistance	0
NRTI, ABC, High-level resistance	0
NRTI, FTC, Susceptible	2
NRTI, FTC, Potential low-level resistance	0
NRTI, FTC, Low-level resistance	0
NRTI, FTC, Intermediate resistance	0
NRTI, FTC, High-level resistance	0
NRTI, TDF, Susceptible	2
NRTI, TDF, Potential low-level resistance	0
NRTI, TDF, Low-level resistance	0
NRTI, TDF, Intermediate resistance	0
NRTI, TDF, High-level resistance	0
NRTI, ZDV, Susceptible	2
NRTI, ZDV, Potential low-level resistance	0
NRTI, ZDV, Low-level resistance	0
NRTI, ZDV, Intermediate resistance	0
NRTI, ZDV, High-level resistance	0
NRTI, d4T, Susceptible	2
NRTI, d4T, Potential low-level resistance	0
NRTI, d4T, Low-level resistance	0
NRTI, d4T, Intermediate resistance	0
NRTI, d4T, High-level resistance	0
NRTI, ddI, Susceptible	2
NRTI, ddI, Potential low-level resistance	0
NRTI, ddI, Low-level resistance	0
NRTI, ddI, Intermediate resistance	0
NRTI, ddI, High-level resistance	0
PI, ATV/r, Susceptible	2
PI, ATV/r, Potential low-level resistance	0
PI, ATV/r, Low-level resistance	0
PI, ATV/r, Intermediate resistance	0
PI, ATV/r, High-level resistance	0
PI, DRV/r, Susceptible	2
PI, DRV/r, Potential low-level resistance	0
PI, DRV/r, Low-level resistance	0
PI, DRV/r, Intermediate resistance	0
PI, DRV/r, High-level resistance	0
PI, FPV/r, Susceptible	2
PI, FPV/r, Potential low-level resistance	0
PI, FPV/r, Low-level resistance	0
PI, FPV/r, Intermediate resistance	0
PI, FPV/r, High-level resistance	0
PI, IDV/r, Susceptible	2
PI, IDV/r, Potential low-level resistance	0
PI, IDV/r, Low-level resistance	0
PI, IDV/r, Intermediate resistance	0
PI, IDV/r, High-level resistance	0
PI, LPV/r, Susceptible	2
PI, LPV/r, Potential low-level resistance	0
PI, LPV/r, Low-level resistance	0
PI, LPV/r, Intermediate resistance	0
PI, LPV/r, High-level resistance	0
PI, NFV, Susceptible	2
PI, NFV, Potential low-level resistance	0
PI, NFV, Low-level resistance	0
PI, NFV, Intermediate resistance	0
PI, NFV, High-level resistance	0
PI, RTV, Susceptible	2
PI, RTV, Potential low-level resistance	0
PI, RTV, Low-level resistance	0
PI, RTV, Intermediate resistance	0
PI, RTV, High-level resistance	0
PI, SQV/r, Susceptible	2
PI, SQV/r, Potential low-level resistance	0
PI, SQV/r, Low-level resistance	0
PI, SQV/r, Intermediate resistance	0
PI, SQV/r, High-level resistance	0
PI, TPV/r, Susceptible	2
PI, TPV/r, Potential low-level resistance	0
PI, TPV/r, Low-level resistance	0
PI, TPV/r, Intermediate resistance	0
PI, TPV/r, High-level resistance	0

Notes
[59] - CVW resistance Population

No statistical analyses for this end point

Secondary: Number of participants with genotypic resistance-CAR Late Switch Group through Late Switch Phase

Top of page

End point title

Number of participants with genotypic resistance-CAR Late Switch Group through Late Switch Phase

End point description

Plasma samples were collected for drug resistance testing. Genotypic Resistance data for the following drugs (DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r) in participants Meeting CVW Criteria has been presented. Late Switch (LS) CVW resistance Population comprised of all participants in the LS-ITT-E Population who met CVW through the end of visit window (Week 48, Week 100 or Week 148) and had available on-treatment genotypic resistance data at the time CVW criterion is met.

End point type

Secondary

End point timeframe

Post-LS Baseline (Week 52) up to Week 148

End point values	Current antiretroviral regimen
Number of subjects analysed	239 ^[60]
Units: Participants
INI, DTG, Susceptible	1
INI, DTG, Potential low-level resistance	0
INI, DTG, Low-level resistance	0
INI, DTG, Intermediate resistance	0
INI, DTG, High-level resistance	0
INI, EVG, Susceptible	1
INI, EVG, Potential low-level resistance	0
INI, EVG, Low-level resistance	0
INI, EVG, Intermediate resistance	0
INI, EVG, High-level resistance	0
INI, RAL, Susceptible	1
INI, RAL, Potential low-level resistance	0
INI, RAL, Low-level resistance	0
INI, RAL, Intermediate resistance	0
INI, RAL, High-level resistance	0
NNRTI, DLV, Susceptible	1
NNRTI, DLV, Potential low-level resistance	0
NNRTI, DLV, Low-level resistance	0
NNRTI, DLV, Intermediate resistance	0
NNRTI, DLV, High-level resistance	0
NNRTI, EFV, Susceptible	0
NNRTI, EFV, Potential low-level resistance	0
NNRTI, EFV, Low-level resistance	0
NNRTI, EFV, Intermediate resistance	0
NNRTI, EFV, High-level resistance	1
NNRTI, ETR, Susceptible	0
NNRTI, ETR, Potential low-level resistance	0
NNRTI, ETR, Low-level resistance	0
NNRTI, ETR, Intermediate resistance	1
NNRTI, ETR, High-level resistance	0
NNRTI, NVP, Susceptible	0
NNRTI, NVP, Potential low-level resistance	0
NNRTI, NVP, Low-level resistance	0
NNRTI, NVP, Intermediate resistance	0
NNRTI, NVP, High-level resistance	1
NNRTI, RPV, Susceptible	0
NNRTI, RPV, Potential low-level resistance	0
NNRTI, RPV, Low-level resistance	0
NNRTI, RPV, Intermediate resistance	0
NNRTI, RPV, High-level resistance	1
NRTI, 3TC, Susceptible	1
NRTI, 3TC, Potential low-level resistance	0
NRTI, 3TC, Low-level resistance	0
NRTI, 3TC, Intermediate resistance	0
NRTI, 3TC, High-level resistance	0
NRTI, ABC, Susceptible	1
NRTI, ABC, Potential low-level resistance	0
NRTI, ABC, Low-level resistance	0
NRTI, ABC, Intermediate resistance	0
NRTI, ABC, High-level resistance	0
NRTI, FTC, Susceptible	1
NRTI, FTC, Potential low-level resistance	0
NRTI, FTC, Low-level resistance	0
NRTI, FTC, Intermediate resistance	0
NRTI, FTC, High-level resistance	0
NRTI, TDF, Susceptible	1
NRTI, TDF, Potential low-level resistance	0
NRTI, TDF, Low-level resistance	0
NRTI, TDF, Intermediate resistance	0
NRTI, TDF, High-level resistance	0
NRTI, ZDV, Susceptible	1
NRTI, ZDV, Potential low-level resistance	0
NRTI, ZDV, Low-level resistance	0
NRTI, ZDV, Intermediate resistance	0
NRTI, ZDV, High-level resistance	0
NRTI, d4T, Susceptible	1
NRTI, d4T, Potential low-level resistance	0
NRTI, d4T, Low-level resistance	0
NRTI, d4T, Intermediate resistance	0
NRTI, d4T, High-level resistance	0
NRTI, ddI, Susceptible	1
NRTI, ddI, Potential low-level resistance	0
NRTI, ddI, Low-level resistance	0
NRTI, ddI, Intermediate resistance	0
NRTI, ddI, High-level resistance	0
PI, ATV/r, Susceptible	1
PI, ATV/r, Potential low-level resistance	0
PI, ATV/r, Low-level resistance	0
PI, ATV/r, Intermediate resistance	0
PI, ATV/r, High-level resistance	0
PI, DRV/r, Susceptible	1
PI, DRV/r, Potential low-level resistance	0
PI, DRV/r, Low-level resistance	0
PI, DRV/r, Intermediate resistance	0
PI, DRV/r, High-level resistance	0
PI, FPV/r, Susceptible	1
PI, FPV/r, Potential low-level resistance	0
PI, FPV/r, Low-level resistance	0
PI, FPV/r, Intermediate resistance	0
PI, FPV/r, High-level resistance	0
PI, IDV/r, Susceptible	1
PI, IDV/r, Potential low-level resistance	0
PI, IDV/r, Low-level resistance	0
PI, IDV/r, Intermediate resistance	0
PI, IDV/r, High-level resistance	0
PI, LPV/r, Susceptible	1
PI, LPV/r, Potential low-level resistance	0
PI, LPV/r, Low-level resistance	0
PI, LPV/r, Intermediate resistance	0
PI, LPV/r, High-level resistance	0
PI, NFV, Susceptible	1
PI, NFV, Potential low-level resistance	0
PI, NFV, Low-level resistance	0
PI, NFV, Intermediate resistance	0
PI, NFV, High-level resistance	0
PI, RTV, Susceptible	1
PI, RTV, Potential low-level resistance	0
PI, RTV, Low-level resistance	0
PI, RTV, Intermediate resistance	0
PI, RTV, High-level resistance	0
PI, SQV/r, Susceptible	1
PI, SQV/r, Potential low-level resistance	0
PI, SQV/r, Low-level resistance	0
PI, SQV/r, Intermediate resistance	0
PI, SQV/r, High-level resistance	0
PI, TPV/r, Susceptible	1
PI, TPV/r, Potential low-level resistance	0
PI, TPV/r, Low-level resistance	0
PI, TPV/r, Intermediate resistance	0
PI, TPV/r, High-level resistance	0

Notes
[60] - Late Switch CVW resistance Population

No statistical analyses for this end point

Secondary: Number of participants with phenotypic resistance-Early switch Phase

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End point title

Number of participants with phenotypic resistance-Early switch Phase

End point description

Plasma samples were collected for drug resistance testing. Phenotypic Resistance data for the following drugs (DTG, RAL, EVG, RPV, ETR, 3TC, ABC, FTC, TDF, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, SQV/r, TPV/r) in participants Meeting CVW criteria has been presented.

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	1 ^[61]	0 ^[62]
Units: Participants
NNRTI, RPV, Resistant	0
NNRTI, RPV, Sensitive	1
NNRTI, ETR, Resistant	0
NNRTI, ETR, Partially Sensitive	0
NNRTI, ETR, Sensitive	1
NNRTI, DLV, Resistant	0
NNRTI, DLV, Sensitive	1
NNRTI, EFV, Resistant	0
NNRTI, EFV, Sensitive	1
NNRTI, NVP, Resistant	0
NNRTI, NVP, Sensitive	1
NRTI, 3TC, Resistant	0
NRTI, 3TC, Sensitive	1
NRTI, ABC, Resistant	0
NRTI, ABC, Partially Sensitive	0
NRTI, ABC, Sensitive	1
NRTI, TDF, Resistant	0
NRTI, TDF, Partially Sensitive	0
NRTI, TDF, Sensitive	1
NRTI, d4T, Resistant	0
NRTI, d4T, Sensitive	1
NRTI, ddI, Resistant	0
NRTI, ddI, Partially Sensitive	0
NRTI, ddI, Sensitive	1
NRTI, FTC, Resistant	0
NRTI, FTC, Sensitive	1
NRTI, ZDV, Resistant	0
NRTI, ZDV, Sensitive	1
PI, ATV/r, Resistant	0
PI, ATV/r, Sensitive	1
PI, DRV/r, Resistant	0
PI, DRV/r, Partially Sensitive	0
PI, DRV/r, Sensitive	1
PI, FPV/r, Resistant	0
PI, FPV/r, Partially Sensitive	0
PI, FPV/r, Sensitive	1
PI, IDV/r, Resistant	0
PI, IDV/r, Sensitive	1
PI, LPV/r, Resistant	0
PI, LPV/r, Partially Sensitive	0
PI, LPV/r, Sensitive	1
PI, SQV/r, Resistant	0
PI, SQV/r, Partially Sensitive	0
PI, SQV/r, Sensitive	1
PI, TPV/r, Resistant	0
PI, TPV/r, Partially Sensitive	0
PI, TPV/r, Sensitive	1
PI, NFV, Resistant	0
PI, NFV, Sensitive	1
PI, RTV, Resistant	0
PI, RTV, Sensitive	1

Notes
[61] - CVW resistance Population
[62] - CVW resistance Population

No statistical analyses for this end point

Secondary: Number of participants with phenotypic resistance-DTG+RPV early switch group through Early and Late Switch Phase

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End point title

Number of participants with phenotypic resistance-DTG+RPV early switch group through Early and Late Switch Phase ^[63]

End point description

Plasma samples were collected for drug resistance testing. Phenotypic Resistance data for the following drugs (DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r) in participants Meeting CVW criteria has been presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Up to Week 148

Notes
[63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were performed.

End point values	DTG + RPV
Number of subjects analysed	2 ^[64]
Units: Participants
INI, DTG, Resistant, n=1	0
INI, DTG, Partially Sensitive, n=1	0
INI, DTG, Sensitive, n=1	1
INI, EVG, Resistant, n=1	0
INI, EVG, Partially sensitive, n=1	0
INI, EVG, Sensitive, n=1	1
INI, RAL, Resistant, n=1	1
INI, RAL, Partially sensitive, n=1	0
INI, RAL, Sensitive, n=1	0
NNRTI, DLV, Resistant, n=2	1
NNRTI, DLV, Partially Sensitive, n=2	0
NNRTI, DLV, Sensitive, n=2	1
NNRTI, EFV, Resistant, n=2	1
NNRTI, EFV, Partially sensitive, n=2	0
NNRTI, EFV, Sensitive, n=2	1
NNRTI, ETR, Resistant, n=2	1
NNRTI, ETR, Partially sensitive, n=2	0
NNRTI, ETR, Sensitive, n=2	1
NNRTI, NVP, Resistant, n=2	1
NNRTI, NVP, Partially sensitive, n=2	0
NNRTI, NVP, Sensitive, n=2	1
NNRTI, RPV, Resistant, n=2	1
NNRTI, RPV, Partially sensitive, n=2	0
NNRTI, RPV, Sensitive, n=2	1
NRTI, 3TC, Resistant, n=2	0
NRTI, 3TC, Partially sensitive, n=2	0
NRTI, 3TC, Sensitive, n=2	2
NRTI, ABC, Resistant, n=2	0
NRTI, ABC, Partially sensitive, n=2	0
NRTI, ABC, Sensitive, n=2	2
NRTI, FTC, Resistant, n=2	0
NRTI, FTC, Partially sensitive, n=2	0
NRTI, FTC, Sensitive, n=2	2
NRTI, TDF, Resistant, n=2	0
NRTI, TDF, Partially sensitive, n=2	0
NRTI, TDF, Sensitive, n=2	2
NRTI, ZDV, Resistant, n=2	0
NRTI, ZDV, Partially sensitive, n=2	0
NRTI, ZDV, Sensitive, n=2	2
NRTI, d4T, Resistant, n=2	0
NRTI, d4T, Partially sensitive, n=2	0
NRTI, d4T, Sensitive, n=2	2
NRTI, ddI, Resistant, n=2	0
NRTI, ddI, Partially sensitive, n=2	0
NRTI, ddI, Sensitive, n=2	2
PI, ATV/r, Resistant, n=2	0
PI, ATV/r, Partially sensitive, n=2	0
PI, ATV/r, Sensitive, n=2	2
PI, DRV/r, Resistant, n=2	0
PI, DRV/r, Partially sensitive, n=2	0
PI, DRV/r, Sensitive, n=2	2
PI, FPV/r, Resistant, n=2	0
PI, FPV/r, Partially sensitive, n=2	0
PI, FPV/r, Sensitive, n=2	2
PI, IDV/r, Resistant, n=2	0
PI, IDV/r, Partially sensitive, n=2	0
PI, IDV/r, Sensitive, n=2	2
PI, LPV/r, Resistant, n=2	0
PI, LPV/r, Partially sensitive, n=2	0
PI, LPV/r, Sensitive, n=2	2
PI, NFV, Resistant, n=2	0
PI, NFV, Partially sensitive, n=2	0
PI, NFV, Sensitive, n=2	2
PI, RTV, Resistant, n=2	0
PI, RTV, Partially sensitive, n=2	0
PI, RTV, Sensitive, n=2	2
PI, SQV/r, Resistant, n=2	0
PI, SQV/r, Partially sensitive, n=2	0
PI, SQV/r, Sensitive, n=2	2
PI, TPV/r, Resistant, n=2	0
PI, TPV/r, Partially sensitive, n=2	0
PI, TPV/r, Sensitive, n=2	2

Notes
[64] - CVW resistance Population

No statistical analyses for this end point

Secondary: Number of participants with phenotypic resistance-CAR Late Switch Group through Late Switch Phase

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End point title

Number of participants with phenotypic resistance-CAR Late Switch Group through Late Switch Phase

End point description

End point type

Secondary

End point timeframe

Post-LS Baseline (Week 52) up to Week 148

End point values	Current antiretroviral regimen
Number of subjects analysed	1 ^[65]
Units: Participants
NNRTI, DLV, Resistant	1
NNRTI, DLV, Partially Sensitive	0
NNRTI, DLV, Sensitive	0
NNRTI, EFV, Resistant	1
NNRTI, EFV, Partially sensitive	0
NNRTI, EFV, Sensitive	0
NNRTI, ETR, Resistant	0
NNRTI, ETR, Partially sensitive	1
NNRTI, ETR, Sensitive	0
NNRTI, NVP, Resistant	1
NNRTI, NVP, Partially sensitive	0
NNRTI, NVP, Sensitive	0
NNRTI, RPV, Resistant	1
NNRTI, RPV, Partially sensitive	0
NNRTI, RPV, Sensitive	0
NRTI, 3TC, Resistant	0
NRTI, 3TC, Partially sensitive	0
NRTI, 3TC, Sensitive	1
NRTI, ABC, Resistant	0
NRTI, ABC, Partially sensitive	0
NRTI, ABC, Sensitive	1
NRTI, FTC, Resistant	0
NRTI, FTC, Partially sensitive	0
NRTI, FTC, Sensitive	1
NRTI, TDF, Resistant	0
NRTI, TDF, Partially sensitive	0
NRTI, TDF, Sensitive	1
NRTI, ZDV, Resistant	0
NRTI, ZDV, Partially sensitive	0
NRTI, ZDV, Sensitive	1
NRTI, d4T, Resistant	0
NRTI, d4T, Partially sensitive	0
NRTI, d4T, Sensitive	1
NRTI, ddI, Resistant	0
NRTI, ddI, Partially sensitive	0
NRTI, ddI, Sensitive	1
PI, ATV/r, Resistant	0
PI, ATV/r, Partially sensitive	0
PI, ATV/r, Sensitive	1
PI, DRV/r, Resistant	0
PI, DRV/r, Partially sensitive	0
PI, DRV/r, Sensitive	1
PI, FPV/r, Resistant	0
PI, FPV/r, Partially sensitive	0
PI, FPV/r, Sensitive	1
PI, IDV/r, Resistant	0
PI, IDV/r, Partially sensitive	0
PI, IDV/r, Sensitive	1
PI, LPV/r, Resistant	0
PI, LPV/r, Partially sensitive	0
PI, LPV/r, Sensitive	1
PI, NFV, Resistant	0
PI, NFV, Partially sensitive	0
PI, NFV, Sensitive	1
PI, RTV, Resistant	0
PI, RTV, Partially sensitive	0
PI, RTV, Sensitive	1
PI, SQV/r, Resistant	0
PI, SQV/r, Partially sensitive	0
PI, SQV/r, Sensitive	1
PI, TPV/r, Resistant	0
PI, TPV/r, Partially sensitive	0
PI, TPV/r, Sensitive	1

Notes
[65] - LS CVW resistance Population

No statistical analyses for this end point

Secondary: Pre-dose concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 in participants switching to DTG + RPV-DTG+RPV early switch group through Early and Late Switch Phase

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End point title

Pre-dose concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 in participants switching to DTG + RPV-DTG+RPV early switch group through Early and Late Switch Phase

End point description

Two separate blood samples for DTG and RPV were collected pre-dose at Weeks 4, 24, 48, 56, 76 and 100. Pre-dose concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 is summarized for the participants switching to DTG + RPV in the early+late switch phase. Pharmacokinetic (PK) Parameter Population consisted of all participants who received DTG +RPV and provided at least one evaluable estimate of predose concentration (C0). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Pre-dose at Week 4, 24, 48, 56, 76 and 100

End point values	DTG 50 mg PK Parameter Population	RPV 25 mg PK Parameter Population
Number of subjects analysed	254 ^[66]	254 ^[67]
Units: ug/ L
arithmetic mean (standard deviation)
Week 4, n=176, 175	1578.88 ( 1170.967 )	79.50 ( 38.230 )
Week 24, n=207, 207	1447.23 ( 917.677 )	90.21 ( 46.302 )
Week 48, n=215, 215	1384.36 ( 889.829 )	91.41 ( 47.073 )
Week 56, n=214, 213	1637.74 ( 1063.391 )	90.55 ( 45.686 )
Week 76, n=219, 219	1507.81 ( 913.263 )	92.51 ( 46.223 )
Week 100, n=220, 221	1532.10 ( 916.975 )	91.98 ( 44.683 )

Notes
[66] - PK Parameter Population
[67] - PK Parameter Population

No statistical analyses for this end point

Secondary: Pre-dose concentrations of DTG and RPV at Weeks 56, 76 and 100 in participants switching to DTG + RPV-CAR Late Switch Group through Late Switch Phase

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End point title

Pre-dose concentrations of DTG and RPV at Weeks 56, 76 and 100 in participants switching to DTG + RPV-CAR Late Switch Group through Late Switch Phase

End point description

Two separate blood samples for DTG and RPV were collected pre-dose at Weeks 56, 76 and 100. Pre-dose concentrations of DTG and RPV at Weeks 56, 76 and 100 is summarized for the participants switching to DTG + RPV in the late switch phase. Late Switch PK Parameter Population comprised of all participants who were randomized to CAR and received DTG + RPV in the Late Switch Phase and provided at least one evaluable estimate of pre-dose concentration (C0). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Pre-dose at Weeks 56, 76 and 100

End point values	CAR-DTG 50 mg LS PK Parameter Population	CAR-RPV 25mg LS PK Parameter Population
Number of subjects analysed	226 ^[68]	226 ^[69]
Units: ug/ L
arithmetic mean (standard deviation)
Week 56, n=203, 203	1544.75 ( 1049.595 )	77.27 ( 38.931 )
Week 76, n=210, 210	1806.77 ( 1019.300 )	91.46 ( 48.568 )
Week 100, n=215, 215	1881.97 ( 1160.587 )	90.89 ( 47.762 )

Notes
[68] - Late Switch PK Parameter Population
[69] - Late Switch PK Parameter Population

No statistical analyses for this end point

Secondary: Pre-dose concentrations of DTG and RPV at Weeks 2, 4 and 8 in the first 20 participants who switch from efavirenz (EFV) or nevirapine (NVP) to DTG + RPV

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End point title

Pre-dose concentrations of DTG and RPV at Weeks 2, 4 and 8 in the first 20 participants who switch from efavirenz (EFV) or nevirapine (NVP) to DTG + RPV

End point description

Two blood samples were collected pre-dose for DTG and RPV at Weeks 2 and 8 only for the first 20 participants who switch from EFV or NVP to DTG+RPV, in addition to the pre-dose blood sample collected at Week 4 for all subjects. One blood sample was collected pre-dose for EFV or NVP at Week 2 for the first 20 participants who switch from EFV or NVP to DTG + RPV. PK Parameter NNRTI Subset Extra Sampling Population consisted of the first approximately 20 participants in the PK Parameter NNRTI Subset population who have extra PK samples at weeks 2 and 8. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Pre-dose at Weeks 2, 4 and 8

End point values	DTG 50 mg PK Parameter NNRTI Subset	RPV 25 mg PK Parameter NNRTI Subset
Number of subjects analysed	28 ^[70]	28 ^[71]
Units: ug/ L
arithmetic mean (standard deviation)
Week 2, n=19, 19	834.58 ( 639.622 )	57.342 ( 29.5436 )
Week 4, n=22, 21	1218.23 ( 842.703 )	78.338 ( 31.4825 )
Week 8, n=26, 26	1472.50 ( 818.774 )	79.652 ( 40.7546 )

Notes
[70] - PK Parameter NNRTI Subset extra sampling Population
[71] - PK Parameter NNRTI Subset extra sampling Population

No statistical analyses for this end point

Secondary: Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 48 using snapshot algorithm by Baseline third agent treatment class

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End point title

Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 48 using snapshot algorithm by Baseline third agent treatment class

End point description

Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 48 using the FDA snapshot algorithm was assessed by Baseline third agent class to assess the impact of Baseline third agent class (INSTI, NNRTI, or PI) on efficacy, safety and tolerability of DTG +RPV compared to continuation of CAR. Plasma samples were collected for HIV-1 RNA at Baseline (Day 1), Week 4, 8, 12, 24, 36 and 48. The analysis was done using cochran-mantel haenszel test stratified by current antiretroviral third-agent class. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[72]	255 ^[73]
Units: Percentage of participants
number (not applicable)
NNRTI, n=144, 144	97	93
INSTI, n=59, 49	92	94
PI, n=58, 62	91	97

Notes
[72] - ITT-E Population
[73] - ITT-E Population

Statistical Analysis 1

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.179 ^[74]

Method

Chi-squared corrected

Confidence interval

Notes
[74] - One-sided p-value from weighted least squares chi-squared statistic. A p-value <=0.10 was used to indicate statistically significant evidence of heterogeneity in the difference in proportions across levels of each analysis strata.

Statistical Analysis 2

Statistical analysis description

NNRTI: No formal non-inferiority margin has been pre-specified for secondary endpoints

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Risk difference (RD)

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

8.6

Statistical Analysis 3

Statistical analysis description

INSTI: No formal non-inferiority margin has been pre-specified for secondary endpoints.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Risk difference (RD)

Point estimate

-2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-12.1

upper limit

7.4

Statistical Analysis 4

Statistical analysis description

PI: No formal non-inferiority margin has been pre-specified for secondary endpoints

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Risk difference (RD)

Point estimate

-5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-13.9

upper limit

3.1

Secondary: Changes from Baseline in CD4+ lymphocyte count at Week 48 by Baseline third agent treatment class

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End point title

Changes from Baseline in CD4+ lymphocyte count at Week 48 by Baseline third agent treatment class

End point description

Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out at Baseline (Day 1) and Week 48 to assess the impact of Baseline third agent class (INSTI, NNRTI, or PI) on efficacy, safety and tolerability of DTG +RPV compared to continuation of CAR. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[75]	255 ^[76]
Units: Cells per mm^3
arithmetic mean (standard deviation)
NNRTI, n=139, 133	49.7 ( 166.40 )	24.3 ( 160.32 )
INSTI, n=53, 46	-11.2 ( 176.56 )	10.3 ( 155.53 )
PI, n=53, 61	10.5 ( 163.67 )	12.2 ( 163.32 )

Notes
[75] - ITT-E Population
[76] - ITT-E Population

No statistical analyses for this end point

Secondary: Number of participants with any AE, AELD or AE with grade 1, 2, 3 or 4 toxicity over 48 weeks by Baseline third agent treatment class

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End point title

Number of participants with any AE, AELD or AE with grade 1, 2, 3 or 4 toxicity over 48 weeks by Baseline third agent treatment class

End point description

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any AE, AELD or AE with maximum grade toxicity experienced by any one participant over 48 weeks by Baseline third agent class (INSTI, NNRTI, or PI) is summarized. AEs were graded using the Division of AIDS grading. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Up to 48 weeks

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[77]	255 ^[78]
Units: Participants
Any AE, NNRTI, n=144, 144	106	96
Any AE, INSTI, n=59, 49	47	36
Any AE, PI, n=58, 62	42	42
NNRTI, Maximum toxicity Grade 1 AE, n=144, 144	68	76
NNRTI, Maximum toxicity Grade 2 AE, n=144, 144	30	19
NNRTI, Maximum toxicity Grade 3 AE, n=144, 144	8	0
NNRTI, Maximum toxicity Grade 4 AE, n=144, 144	0	1
INSTI, Maximum toxicity Grade 1 AE, n=59, 49	27	20
INSTI, Maximum toxicity Grade 2 AE, n=59, 49	15	15
INSTI, Maximum toxicity Grade 3 AE, n=59, 49	5	1
INSTI, Maximum toxicity Grade 4 AE, n=59, 49	0	0
PI, Maximum toxicity Grade 1 AE, n=58, 62	24	26
PI, Maximum toxicity Grade 2 AE, n=58, 62	14	13
PI, Maximum toxicity Grade 3 AE, n=58, 62	3	3
PI, Maximum toxicity Grade 4 AE, n=58, 62	1	0
AELD, NNRTI, n=144, 144	5	1
AELD, INSTI, n=59, 49	4	0
AELD, PI, n=58, 62	3	0

Notes
[77] - Safety Population
[78] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with maximum post-baseline emergent chemistry toxicities over 48 weeks by Baseline third agent treatment class

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End point title

Number of participants with maximum post-baseline emergent chemistry toxicities over 48 weeks by Baseline third agent treatment class

End point description

Blood samples were collected at Baseline (Day 1) and at Weeks 4, 8, 12, 24, 36 and 48 to evaluate ALT, albumin, ALP, AST, total bilirubin, chloride, creatinine, glucose, potassium, phosphate, sodium, BUN, total carbon dioxide, lipase, creatine phosphokinase and creatinine clearance. Number of participants who experienced maximum toxicity grade post-baseline in chemistry parameters over 48 weeks by Baseline third agent treatment class (INSTI, NNRTI, PI) is summarized. Clinical chemistry toxicities were graded using the DAIDS grading. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Up to 48 weeks

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[79]	255 ^[80]
Units: Participants
NNRTI, Grade 1, n=144, 144	51	52
NNRTI, Grade 2, n=144, 144	31	40
NNRTI, Grade 3, n=144, 144	7	4
NNRTI, Grade 4, n=144, 144	1	5
INSTI, Grade 1, n= 59, 49	19	11
INSTI, Grade 2, n=59, 49	23	18
INSTI, Grade 3, n= 59, 49	3	3
INSTI, Grade 4, n= 59, 49	0	2
PI, Grade 1, n= 58, 62	22	17
PI, Grade 2, n= 58, 62	18	21
PI, Grade 3, n= 58, 62	1	9
PI, Grade 4, n= 58, 62	0	3

Notes
[79] - Safety Population
[80] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with maximum post-baseline emergent hematology toxicities over 48 weeks by Baseline third agent treatment class

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End point title

Number of participants with maximum post-baseline emergent hematology toxicities over 48 weeks by Baseline third agent treatment class

End point description

Blood samples were collected at Baseline (Day 1) and at Weeks 4, 8, 12, 24, 36 and 48 to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, MCV, RBC count, WBC count and platelet count. Number of participants who experienced maximum toxicity grade post-baseline in hematology parameters over 48 weeks by Baseline third agent treatment class (INSTI, NNRTI, PI) was summarized. Hematology toxicities were graded using the DAIDS grading. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).

End point type

Secondary

End point timeframe

Up to 48 weeks

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[81]	255 ^[82]
Units: Participants
NNRTI; Grade 1; n= 144, 144	7	6
NNRTI; Grade 2; n= 144, 144	1	2
NNRTI; Grade 3; n= 144, 144	1	0
NNRTI; Grade 4; n= 144, 144	1	0
INI; Grade 1; n-= 59, 49	1	1
INI; Grade 2; n-= 59, 49	0	0
INI; Grade 3; n-= 59, 49	0	0
INI; Grade 4; n-= 59, 49	0	0
PI; Grade 1; n= 58, 62	3	4
PI; Grade 2; n= 58, 62	1	0
PI; Grade 3; n= 58, 62	2	0
PI; Grade 4; n= 58, 62	0	0

Notes
[81] - Safety Population
[82] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with observed genotypic resistance for participants meeting virologic withdrawal criteria by Baseline third agent treatment class

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End point title

Number of participants with observed genotypic resistance for participants meeting virologic withdrawal criteria by Baseline third agent treatment class

End point description

For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were to be analyzed in an attempt to obtain genotype data on as many samples as possible. Samples for drug resistance testing (genotypic) were to be collected at Day 1. Number of participants with genotypic resistance to CAR and to DTG or RPV for those meeting virologic withdrawal criteria in subgroups stratified based on Baseline third agent treatment class (INSTI, NNRTI, PI) were to be summarized. This outcome has not been analyzed as the number of participants was low (1 CVW per arm) and summaries by Baseline third agent were not provided. Therefore, data are not available for this outcome measure due to the insufficient number of participants with events.

End point type

Secondary

End point timeframe

Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	0 ^[83]	0 ^[84]
Units: Participants

Notes
[83] - CVW resistance Population
[84] - CVW resistance Population

No statistical analyses for this end point

Secondary: Number of participants with observed phenotypic resistance for participants meeting virologic withdrawal criteria by Baseline third agent treatment class

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End point title

Number of participants with observed phenotypic resistance for participants meeting virologic withdrawal criteria by Baseline third agent treatment class

End point description

For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were to be analyzed in an attempt to obtain phenotype data on as many samples as possible. Samples for drug resistance testing (phenotypic) were to be collected at Day 1. Number of participants with phenotypic resistance to CAR and to DTG or RPV for those meeting virologic withdrawal criteria in subgroups stratified based on Baseline third agent treatment class (INSTI, NNRTI, PI) were to be summarized. This outcome was not analyzed as the number of participants was low (1 CVW per arm) and summaries by Baseline third agent were not provided. Therefore, data are not available for this outcome measure due to the insufficient number of participants with events.

End point type

Secondary

End point timeframe

Week 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	0 ^[85]	0 ^[86]
Units: Participants

Notes
[85] - CVW resistance Population
[86] - CVW resistance Population

No statistical analyses for this end point

Secondary: Change from Baseline in fasting lipids at Weeks 24 and 48 by Baseline third agent treatment class

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End point title

Change from Baseline in fasting lipids at Weeks 24 and 48 by Baseline third agent treatment class

End point description

Blood samples were collected at Baseline (Day 1), Weeks 24 and 48 to assess fasting lipids which included total cholesterol (CHO), LDL cholesterol, HDL cholesterol and triglycerides. Change from Baseline was calculated as value at indicated time point minus Baseline value. 99999 indicates data could not be calculated due to insufficient participants. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1), Weeks 24 and 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[87]	255 ^[88]
Units: mmol/ L
arithmetic mean (standard deviation)
CHO, Week 24, overall, n=237, 229	1.015 ( 15.7472 )	1.300 ( 12.2269 )
CHO, Week 48, overall, n=237, 230	-0.165 ( 15.9301 )	0.194 ( 13.1071 )
CHO, Week 24, NNRTI, n=0, 132	99999 ( 99999 )	1.238 ( 12.4889 )
CHO, Week 48, NNRTI, n=0, 128	99999 ( 99999 )	0.281 ( 12.2469 )
CHO, Week 24, INSTI, n=0, 42	99999 ( 99999 )	1.973 ( 12.1365 )
CHO, Week 48, INSTI, n=0, 44	99999 ( 99999 )	2.798 ( 16.1468 )
CHO, Week 24, PI, n=0, 55	99999 ( 99999 )	0.936 ( 11.8530 )
CHO, Week 48, PI, n=0, 58	99999 ( 99999 )	-1.971 ( 12.2195 )
HDL CHO direct, Overall, Week 24, n=237, 229	0.557 ( 19.4929 )	-2.533 ( 16.3641 )
HDL CHO direct, Overall, Week 48, n=237,230	6.384 ( 20.9244 )	4.723 ( 18.3253 )
HDL CHO direct, NNRTI, Week 24, n=0, 132	99999 ( 99999 )	-2.562 ( 15.3521 )
HDL CHO direct, NNRTI, Week 48, n=0, 128	99999 ( 99999 )	4.307 ( 17.8013 )
HDL CHO direct, INSTI, Week 24, n=0, 42	99999 ( 99999 )	-3.097 ( 20.0002 )
HDL CHO direct, INSTI, Week 48, n=0, 44	99999 ( 99999 )	5.386 ( 20.6791 )
HDL CHO direct, PI, Week 24, n=0, 55	99999 ( 99999 )	-2.031 ( 15.9582 )
HDL CHO direct, PI, Week 48, n=0, 58	99999 ( 99999 )	5.140 ( 17.8779 )
LDL CHO calculation, Overall, Week 24, n=231, 221	5.838 ( 22.9614 )	4.395 ( 21.6685 )
LDL CHO calculation, Overall, Week 48, n=229, 220	1.137 ( 23.3849 )	-0.598 ( 20.6931 )
LDL CHO calculation, NNRTI, Week 24, n=0, 129	99999 ( 99999 )	5.959 ( 21.5692 )
LDL CHO calculation, NNRTI, Week 48, n=0, 124	99999 ( 99999 )	0.747 ( 19.2299 )
LDL CHO calculation, INSTI, Week 24, n=0, 40	99999 ( 99999 )	3.787 ( 17.6755 )
LDL CHO calculation, INSTI, Week 48, n=0, 42	99999 ( 99999 )	2.647 ( 24.0430 )
LDL CHO calculation, PI, Week 24, n=0, 52	99999 ( 99999 )	0.983 ( 24.5052 )
LDL CHO calculation, PI, Week 48, n=0, 54	99999 ( 99999 )	-6.212 ( 20.4774 )
Triglycerides, Overall, Week 24, n=237, 229	-0.825 ( 42.5565 )	9.379 ( 45.5529 )
Triglycerides, Overall, Week 48, n=237, 230	1.169 ( 51.9844 )	7.183 ( 44.7044 )
Triglycerides, NNRTI, Week 24, n=0, 132	99999 ( 99999 )	4.962 ( 40.6201 )
Triglycerides, NNRTI, Week 48, n=0, 128	99999 ( 99999 )	5.248 ( 41.7728 )
Triglycerides, INSTI, Week 24, n=0, 42	99999 ( 99999 )	18.204 ( 47.2348 )
Triglycerides, INSTI, Week 48, n=0, 44	99999 ( 99999 )	14.627 ( 56.2824 )
Triglycerides, PI, Week 24, n=0,55	99999 ( 99999 )	13.241 ( 54.2327 )
Triglycerides, PI, Week 48, n=0, 58	99999 ( 99999 )	5.806 ( 41.2106 )

Notes
[87] - Safety Population
[88] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 4, 24 and 48-Early Switch Phase

Top of page

End point title

Change from Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 4, 24 and 48-Early Switch Phase

End point description

Symptom Distress Module, also called HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Symptom count is based on which of the 20 symptoms were present in the participant and is the sum of the number of symptoms present and ranges from 0 (none) to 20 (all). Symptom bother score is based on the score for each symptom present ranging from 1 (it doesn't bother me) to 4 (it bothers me a lot). Symptom bother score is the unweighted sum of the bother item scores for each symptom. Symptom bother score ranges from 0 (minimum) to 80 (maximum). Last observation carried forward (LOCF) was used as primary method of analysis. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) Weeks 4, 24 and 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[89]	255 ^[90]
Units: Scores on a scale
arithmetic mean (standard deviation)
Symptom count, Week 4, n=224, 229	-1.1 ( 4.11 )	-0.8 ( 4.02 )
Symptom count, Week 24, n=228, 232	-0.7 ( 4.31 )	-0.8 ( 4.64 )
Symptom count, Week 48, n=228, 231	-0.5 ( 4.33 )	-0.4 ( 4.82 )
Symptom Bother Score, Week 4, n=224, 229	-2.8 ( 7.44 )	-1.8 ( 7.24 )
Symptom Bother Score, Week 24, n=228, 232	-1.8 ( 8.40 )	-1.7 ( 8.72 )
Symptom Bother Score, Week 48, n=228, 231	-1.5 ( 7.97 )	-0.7 ( 9.30 )

Notes
[89] - ITT-E Population
[90] - ITT-E Population

Statistical Analysis 1

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.43 ^[91]

Method

ANCOVA

Confidence interval

Notes
[91] - P-value for interaction between treatment group and Baseline symptom bother score (Week 4)

Statistical Analysis 2

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for age, Baseline third agent, gender, race and Baseline score.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.039 ^[92]

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.239

Confidence interval

level

95%

sides

2-sided

lower limit

-2.414

upper limit

-0.064

Notes
[92] - P value to assess difference between treatment groups (Symptom Bother Score - Week 4)

Statistical Analysis 3

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.542 ^[93]

Method

ANCOVA

Confidence interval

Notes
[93] - P-value for interaction between treatment group and Baseline symptom bother score (Week 24)

Statistical Analysis 4

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for age, Baseline third agent, gender, race and Baseline score.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.448 ^[94]

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.528

Confidence interval

level

95%

sides

2-sided

lower limit

-1.896

upper limit

0.84

Notes
[94] - P value to assess difference between treatment groups (Symptom Bother Score - Week 24)

Statistical Analysis 5

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.402 ^[95]

Method

ANCOVA

Confidence interval

Notes
[95] - P-value for interaction between treatment group and Baseline symptom bother score (Week 48)

Statistical Analysis 6

Statistical analysis description

Estimates are calculated from an ANCOVA model adjusting for age, Baseline third agent, gender, race and Baseline score.

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.164 ^[96]

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.037

Confidence interval

level

95%

sides

2-sided

lower limit

-2.501

upper limit

0.426

Notes
[96] - P value to assess difference between treatment groups (Symptom Bother Score - Week 48)

Secondary: Change from Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 56, 76, 100 and 148-DTG+RPV early switch group through Early and Late Switch Phase

Top of page

End point title

Change from Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 56, 76, 100 and 148-DTG+RPV early switch group through Early and Late Switch Phase ^[97]

End point description

The Symptom Distress Module, also called the HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Symptom count is based on which of the 20 symptoms were present in the participant. Symptom count is the sum of the number of symptoms present and ranges from 0 (none) to 20 (all). Symptom bother score is based on the score for each symptom present ranging from 1 (it doesn't bother me) to 4 (it bothers me a lot). Symptom bother score is the unweighted sum of the bother item scores for each symptom. The symptom bother score ranges from 0 (minimum bother score) to 80 (maximum bother score). LOCF was used as primary method of analysis. Change from Baseline is calculated as the value at specified time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Weeks 56, 76, 100 and 148

Notes
[97] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were performed.

End point values	DTG + RPV
Number of subjects analysed	228 ^[98]
Units: Scores on a scale
arithmetic mean (standard deviation)
Symptom count, Week 56	-0.8 ( 4.80 )
Symptom count, Week 76	-0.6 ( 4.66 )
Symptom count, Week 100	-0.5 ( 5.03 )
Symptom count, Week 148	-0.7 ( 4.87 )
Symptom Bother Score, Week 56	-1.8 ( 9.23 )
Symptom Bother Score, Week 76	-1.6 ( 8.70 )
Symptom Bother Score, Week 100	-1.4 ( 9.40 )
Symptom Bother Score, Week 148	-1.7 ( 9.54 )

Notes
[98] - ITT-E Population

No statistical analyses for this end point

Secondary: Change from LS Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 56, 76, 100 and 148-CAR Late Switch Group through Late Switch Phase

Top of page

End point title

Change from LS Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 56, 76, 100 and 148-CAR Late Switch Group through Late Switch Phase

End point description

The Symptom Distress Module, also called the HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Symptom count is based on which of the 20 symptoms were present in the participant. Symptom count is the sum of the number of symptoms present and ranges from 0 (none) to 20 (all). Symptom bother score is based on the score for each symptom present ranging from 1 (it doesn't bother me) to 4 (it bothers me a lot). Symptom bother score is the unweighted sum of the bother item scores for each symptom. The symptom bother score ranges from 0 (minimum) to 80 (maximum). LOCF was used as primary method of analysis. Change from LS Baseline is calculated as the value at specified time point minus LS Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

LS Baseline (Week 48), Weeks 56, 76, 100 and 148

End point values	Current antiretroviral regimen
Number of subjects analysed	239 ^[99]
Units: Scores on a scale
arithmetic mean (standard deviation)
Symptom count, Week 56, n=216	-0.9 ( 4.74 )
Symptom count, Week 76, n=220	-0.7 ( 4.29 )
Symptom count, Week 100, n=220	-0.4 ( 5.04 )
Symptom count, Week 148, n=220	-0.6 ( 4.81 )
Symptom Bother Score, Week 56 n=216	-2.1 ( 7.56 )
Symptom Bother Score, Week 76, n=220	-1.0 ( 7.61 )
Symptom Bother Score, Week 100, n=220	-0.8 ( 8.43 )
Symptom Bother Score, Week 148, n=220	-1.0 ( 8.54 )

Notes
[99] - LS ITT-E Population

No statistical analyses for this end point

Secondary: Change from Baseline treatment satisfaction using the HIV treatment satisfaction questionnaire (HIV TSQ) at Weeks 4, 24 and 48-Early Switch Phase

Top of page

End point title

Change from Baseline treatment satisfaction using the HIV treatment satisfaction questionnaire (HIV TSQ) at Weeks 4, 24 and 48-Early Switch Phase

End point description

The HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0 (very dissatisfied, inconvenient) to 6 (very satisfied, convenient). The items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscale scores: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). Higher scores indicated greater treatment satisfaction as compared to the past few weeks. The HIV TSQ was administered as a paper questionnaire. Change from Baseline is calculated as the value at specified time point minus Baseline value. Total score, lifestyle/ease score and General satisfaction/clinical sub-score (CS) have been summarized. LOCF was used as primary method of analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1), Weeks 4, 24 and 48

End point values	DTG + RPV	Current antiretroviral regimen
Number of subjects analysed	261 ^[100]	255 ^[101]
Units: Score on a scale
median (full range (min-max))
Total score, Week 4, n=253, 250	0.0 (-21 to 23)	0.0 (-22 to 22)
Total score, Week 24, n=257, 252	0.0 (-27 to 23)	0.0 (-24 to 24)
Total score, Week 48, n=257, 251	0.0 (-27 to 25)	0.0 (-50 to 23)
lifestyle/ease Sub-score, Week 4, n=252, 249	0.0 (-11 to 15)	0.0 (-11 to 7)
lifestyle/ease Sub-score, Week 24, n=257, 251	0.0 (-18 to 14)	0.0 (-17 to 10)
lifestyle/ease Sub-score, Week 48, n=257, 250	0.0 (-18 to 12)	0.0 (-21 to 11)
General Satisfaction/CS, Week 4, n=253, 250	0.0 (-13 to 14)	0.0 (-17 to 15)
General Satisfaction/CS, Week 24, n=257, 252	0.0 (-12 to 12)	0.0 (-15 to 15)
General Satisfaction/CS, Week 48, n=257, 251	0.0 (-13 to 14)	0.0 (-29 to 14)

Notes
[100] - ITT-E Population
[101] - ITT-E Population

Statistical Analysis 1

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.037 ^[102]

Method

Wilcoxon rank sum test

Confidence interval

Notes
[102] - P-value to assess HIVTSQs Total Score difference between treatment groups (Week 4)

Statistical Analysis 2

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.101 ^[103]

Method

Wilcoxon rank sum test

Confidence interval

Notes
[103] - P-value to assess HIVTSQs Total Score difference between treatment groups (Week 24)

Statistical Analysis 3

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.042 ^[104]

Method

Wilcoxon rank sum test

Confidence interval

Notes
[104] - P-value to assess HIVTSQs Total score difference between treatment groups (Week 48)

Statistical Analysis 4

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.132 ^[105]

Method

Wilcoxon rank sum test

Confidence interval

Notes
[105] - P-value to assess HIVTSQs lifestyle/ease sub- score difference between treatment groups (Week 4)

Statistical Analysis 5

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.022 ^[106]

Method

Wilcoxon rank sum test

Confidence interval

Notes
[106] - P-value to assess HIVTSQs lifestyle/ease sub- score difference between treatment groups (Week 24)

Statistical Analysis 6

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.004 ^[107]

Method

Wilcoxon rank sum test

Confidence interval

Notes
[107] - P-value to assess HIVTSQs lifestyle/ease sub- score difference between treatment groups (Week 48)

Statistical Analysis 7

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.076 ^[108]

Method

Wilcoxon rank sum test

Confidence interval

Notes
[108] - P-value to assess HIVTSQs General satisfaction/CS sub- score difference between treatment groups (Week 4)

Statistical Analysis 8

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.073 ^[109]

Method

Wilcoxon rank sum test

Confidence interval

Notes
[109] - P-value to assess HIVTSQs General satisfaction/CS sub- score difference between treatment groups (Week 24)

Statistical Analysis 9

Comparison groups

DTG + RPV v Current antiretroviral regimen

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

P-value

= 0.547 ^[110]

Method

Wilcoxon rank sum test

Confidence interval

Notes
[110] - P-value to assess HIVTSQs General satisfaction/CS sub- score difference between treatment groups (Week 48)

Secondary: Change from Baseline treatment satisfaction using the HIV TSQ at Weeks 56, 76, 100 and 148-DTG+RPV early switch group through Early and Late Switch Phase

Top of page

End point title

Change from Baseline treatment satisfaction using the HIV TSQ at Weeks 56, 76, 100 and 148-DTG+RPV early switch group through Early and Late Switch Phase ^[111]

End point description

The HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0 (very dissatisfied, inconvenient) to 6 (very satisfied, convenient). The items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscale scores: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). Higher scores indicated greater treatment satisfaction as compared to the past few weeks. The HIV TSQ was administered as a paper questionnaire. Change from Baseline is calculated as the value at specified time point minus Baseline value. Total score, lifestyle/ease score and General satisfaction/CS have been summarized. LOCF was used as primary method of analysis.

End point type

Secondary

End point timeframe

Baseline (Day 1), Weeks 56, 76, 100 and 148

Notes
[111] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were performed.

End point values	DTG + RPV
Number of subjects analysed	257 ^[112]
Units: Score on a scale
median (full range (min-max))
Total score, Week 56	0.0 (-37 to 26)
Total score, Week 76	1.0 (-35 to 26)
Total score, Week 100	0.0 (-27 to 26)
Total score, Week 148	1.0 (-38 to 26)
lifestyle/ease Sub-score, Week 56	0.0 (-21 to 12)
lifestyle/ease Sub-score, Week 76	0.0 (-21 to 12)
lifestyle/ease Sub-score, Week 100	0.0 (-18 to 12)
lifestyle/ease Sub-score, Week 148	0.0 (-18 to 12)
General Satisfaction/CS, Week 56	0.0 (-16 to 14)
General Satisfaction/CS, Week 76	0.0 (-15 to 14)
General Satisfaction/CS, Week 100	0.0 (-15 to 14)
General Satisfaction/CS, Week 148	0.0 (-26 to 14)

Notes
[112] - ITT-E Population

No statistical analyses for this end point

Secondary: Change from LS Baseline treatment satisfaction using the HIV TSQ at Weeks 56, 76, 100 and 148-CAR Late Switch Group through Late Switch Phase

Top of page

End point title

Change from LS Baseline treatment satisfaction using the HIV TSQ at Weeks 56, 76, 100 and 148-CAR Late Switch Group through Late Switch Phase

End point description

The HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0 (very dissatisfied, inconvenient) to 6 (very satisfied, convenient). The items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscale scores: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). Higher scores indicated greater treatment satisfaction as compared to the past few weeks. The HIV TSQ was administered as a paper questionnaire. Change from LS Baseline is calculated as the value at specified time point minus LS Baseline value. Total score, lifestyle/ease score and General satisfaction/CS have been summarized. LOCF was used as primary method of analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

LS Baseline (Week 48), Weeks 56, 76, 100 and 148

End point values	Current antiretroviral regimen
Number of subjects analysed	239 ^[113]
Units: Score on a scale
median (full range (min-max))
Total score, Week 56, n=235	0.0 (-17 to 52)
Total score, Week 76, n=239	0.0 (-26 to 52)
Total score, Week 100, n=239	0.0 (-17 to 51)
Total score, Week 148, n=239	0.0 (-17 to 51)
lifestyle/ease Sub-score, Week 56, n=235	0.0 (-10 to 22)
lifestyle/ease Sub-score, Week 76, n=239	0.0 (-12 to 22)
lifestyle/ease Sub-score, Week 100, n=239	0.0 (-9 to 22)
lifestyle/ease Sub-score, Week 148, n=239	0.0 (-10 to 22)
General Satisfaction/CS, Week 56, n=235	0.0 (-12 to 30)
General Satisfaction/CS, Week 76, n=239	0.0 (-15 to 30)
General Satisfaction/CS, Week 100, n=239	0.0 (-9 to 29)
General Satisfaction/CS, Week 148, n=239	0.0 (-9 to 29)

Notes
[113] - Late Switch ITT-E Population

No statistical analyses for this end point

Other pre-specified: Percentage of participants with plasma HIV-1 RNA <50 c/mL at Weeks 100 and 148 using the Snapshot algorithm-DTG+RPV early switch group through Early and Late Switch Phase

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End point title

Percentage of participants with plasma HIV-1 RNA <50 c/mL at Weeks 100 and 148 using the Snapshot algorithm-DTG+RPV early switch group through Early and Late Switch Phase ^[114]

End point description

Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with plasma HIV 1 RNA < 50 c/mL using the FDA snapshot algorithm was assessed. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest.

End point type

Other pre-specified

End point timeframe

Weeks 100 and 148

Notes
[114] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were performed.

End point values	DTG + RPV
Number of subjects analysed	261 ^[115]
Units: Percentage of participants
number (not applicable)
Week 100	89
Week 148	84

Notes
[115] - ITT-E Population

No statistical analyses for this end point

Other pre-specified: Change from Baseline in CD4+ lymphocyte count at Weeks 100 and 148-DTG+RPV early switch group through Early and Late Switch Phase

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End point title

Change from Baseline in CD4+ lymphocyte count at Weeks 100 and 148-DTG+RPV early switch group through Early and Late Switch Phase ^[116]

End point description

Blood samples were collected for CD4+ cell count assessment by flow cytometry. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).

End point type

Other pre-specified

End point timeframe

Baseline (Day 1), Weeks 100 and 148

Notes
[116] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were performed.

End point values	DTG + RPV
Number of subjects analysed	261 ^[117]
Units: Cells/mm^3
arithmetic mean (standard deviation)
Week 100; n=235	55.9 ( 202.56 )
Week 148; n=221	51.5 ( 205.98 )

Notes
[117] - ITT-E Population

No statistical analyses for this end point

Other pre-specified: Percentage of participants with plasma HIV-1 RNA <50 c/mL at Weeks 100 and 148 using the Snapshot algorithm-CAR Late Switch Group through Late Switch Phase

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End point title

Percentage of participants with plasma HIV-1 RNA <50 c/mL at Weeks 100 and 148 using the Snapshot algorithm-CAR Late Switch Group through Late Switch Phase

End point description

End point type

Other pre-specified

End point timeframe

Weeks 100 and 148

End point values	Current antiretroviral regimen
Number of subjects analysed	239 ^[118]
Units: Percentage of participants
number (not applicable)
Week 100	97
Week 148	93

Notes
[118] - LS ITT-E Population

No statistical analyses for this end point

Other pre-specified: Change from LS Baseline in CD4+ lymphocyte count at Weeks 100 and 148-CAR Late Switch Group through Late Switch Phase

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End point title

Change from LS Baseline in CD4+ lymphocyte count at Weeks 100 and 148-CAR Late Switch Group through Late Switch Phase

End point description

Blood samples were collected for CD4+ cell count assessment by flow cytometry. Change from LS Baseline was calculated as value at indicated time point minus LS Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).

End point type

Other pre-specified

End point timeframe

LS Baseline (Week 48), Weeks 100 and 148

End point values	Current antiretroviral regimen
Number of subjects analysed	239 ^[119]
Units: Cells/mm^3
arithmetic mean (standard deviation)
Week 100; n=231	20.9 ( 173.39 )
Week 148; n=225	6.5 ( 167.44 )

Notes
[119] - LS ITT-E Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Data presented for DTG+RPV (Early Switch) and CAR (Early Switch) represent safety events up to Week 52. Data for DTG+RPV (Early+Late Switch) represents safety events up to Week 148 and CAR (Late Switch) represents safety events from Week 52 to Week 148.

Adverse event reporting additional description

On treatment SAEs and non-serious AEs were reported for the Safety Population for DTG+RPV (Early Switch), CAR (Early Switch) and DTG+RPV (Early+Late Switch). LS Safety Population was used for CAR (Late Switch arm).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

DTG + RPV (Early Switch)

Reporting group description

Participants received DTG 50 milligrams (mg) + RPV 25 mg together once daily at approximately the same time, with a meal, in an open-label fashion up to Week 52 during early switch phase.

Reporting group title

CAR (Early Switch)

Reporting group description

Reporting group title

DTG + RPV (Early + Late Switch)

Reporting group description

Participants received DTG 50 mg + RPV 25 mg together once daily at approximately the same time, with a meal, in an open-label fashion up to Week 52 during early switch phase. Participants continued to receive DTG 50 mg + RPV 25 mg up to Week 148 during the Late Switch Phase.

Reporting group title

CAR (Late Switch)

Reporting group description

At Week 52, participants who received CAR during the early switch phase, with HIV-1 RNA <50 c/mL, switched to DTG 50 mg + RPV 25 mg once daily and were followed until Week 148.

Serious adverse events	DTG + RPV (Early Switch)	CAR (Early Switch)	DTG + RPV (Early + Late Switch)	CAR (Late Switch)
Total subjects affected by serious adverse events
subjects affected / exposed	19 / 261 (7.28%)	9 / 255 (3.53%)	38 / 261 (14.56%)	22 / 239 (9.21%)
number of deaths (all causes)	1	0	2	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Kaposi's sarcoma
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Papillary thyroid cancer
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anal squamous cell carcinoma
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Breast cancer metastatic
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hodgkin's disease
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Invasive ductal breast carcinoma
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Laryngeal cancer stage 0
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to lymph nodes
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thyroid cancer
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	3 / 239 (1.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 261 (0.00%)	1 / 255 (0.39%)	0 / 261 (0.00%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Jarisch-Herxheimer reaction
subjects affected / exposed	0 / 261 (0.00%)	1 / 255 (0.39%)	0 / 261 (0.00%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anaphylactic reaction
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Eosinophilic pneumonia acute
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 261 (0.00%)	1 / 255 (0.39%)	0 / 261 (0.00%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicide attempt
subjects affected / exposed	1 / 261 (0.38%)	1 / 255 (0.39%)	1 / 261 (0.38%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Completed suicide
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Injury, poisoning and procedural complications
Alcohol poisoning
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fibula fracture
subjects affected / exposed	0 / 261 (0.00%)	1 / 255 (0.39%)	0 / 261 (0.00%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Joint injury
subjects affected / exposed	0 / 261 (0.00%)	1 / 255 (0.39%)	0 / 261 (0.00%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	2 / 239 (0.84%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Accidental overdose
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Foreign body in gastrointestinal tract
subjects affected / exposed	0 / 261 (0.00%)	1 / 255 (0.39%)	0 / 261 (0.00%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hand fracture
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ligament rupture
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Procedural pain
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiomyopathy
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Torsade de pointes
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Headache
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Polyneuropathy
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Tympanic membrane perforation
subjects affected / exposed	0 / 261 (0.00%)	1 / 255 (0.39%)	0 / 261 (0.00%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Keratitis
subjects affected / exposed	0 / 261 (0.00%)	1 / 255 (0.39%)	0 / 261 (0.00%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal detachment
subjects affected / exposed	0 / 261 (0.00%)	1 / 255 (0.39%)	0 / 261 (0.00%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal adhesions
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis chronic
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal colic
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Haemarthrosis
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	2 / 261 (0.77%)	0 / 255 (0.00%)	2 / 261 (0.77%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abscess limb
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphogranuloma venereum
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Orchitis
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	2 / 261 (0.77%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Periorbital cellulitis
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	2 / 261 (0.77%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary sepsis
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rotavirus infection
subjects affected / exposed	1 / 261 (0.38%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute hepatitis C
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	2 / 261 (0.77%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abscess
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Carbuncle
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Groin abscess
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis A
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infectious colitis
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	0 / 261 (0.00%)	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Proctitis infectious
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 261 (0.00%)	0 / 255 (0.00%)	1 / 261 (0.38%)	0 / 239 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	DTG + RPV (Early Switch)	CAR (Early Switch)	DTG + RPV (Early + Late Switch)	CAR (Late Switch)
Total subjects affected by non serious adverse events
subjects affected / exposed	121 / 261 (46.36%)	106 / 255 (41.57%)	170 / 261 (65.13%)	132 / 239 (55.23%)
Nervous system disorders
Headache
subjects affected / exposed	17 / 261 (6.51%)	6 / 255 (2.35%)	27 / 261 (10.34%)	14 / 239 (5.86%)
occurrences all number	36	6	57	16
Dizziness
subjects affected / exposed	10 / 261 (3.83%)	0 / 255 (0.00%)	14 / 261 (5.36%)	8 / 239 (3.35%)
occurrences all number	10	0	16	8
General disorders and administration site conditions
Asthenia
subjects affected / exposed	8 / 261 (3.07%)	10 / 255 (3.92%)	14 / 261 (5.36%)	10 / 239 (4.18%)
occurrences all number	8	11	14	12
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	10 / 261 (3.83%)	11 / 255 (4.31%)	17 / 261 (6.51%)	10 / 239 (4.18%)
occurrences all number	13	11	23	12
Dyspepsia
subjects affected / exposed	9 / 261 (3.45%)	3 / 255 (1.18%)	18 / 261 (6.90%)	6 / 239 (2.51%)
occurrences all number	10	4	21	7
Psychiatric disorders
Insomnia
subjects affected / exposed	7 / 261 (2.68%)	4 / 255 (1.57%)	14 / 261 (5.36%)	7 / 239 (2.93%)
occurrences all number	8	4	17	7
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	17 / 261 (6.51%)	7 / 255 (2.75%)	25 / 261 (9.58%)	22 / 239 (9.21%)
occurrences all number	19	7	32	26
Back pain
subjects affected / exposed	6 / 261 (2.30%)	14 / 255 (5.49%)	17 / 261 (6.51%)	22 / 239 (9.21%)
occurrences all number	6	16	23	26
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	19 / 261 (7.28%)	27 / 255 (10.59%)	37 / 261 (14.18%)	30 / 239 (12.55%)
occurrences all number	21	41	53	37
Nasopharyngitis
subjects affected / exposed	21 / 261 (8.05%)	23 / 255 (9.02%)	48 / 261 (18.39%)	37 / 239 (15.48%)
occurrences all number	26	25	86	54
Bronchitis
subjects affected / exposed	17 / 261 (6.51%)	11 / 255 (4.31%)	28 / 261 (10.73%)	19 / 239 (7.95%)
occurrences all number	20	13	39	25
Pharyngitis
subjects affected / exposed	6 / 261 (2.30%)	7 / 255 (2.75%)	15 / 261 (5.75%)	20 / 239 (8.37%)
occurrences all number	8	7	17	24
Influenza
subjects affected / exposed	10 / 261 (3.83%)	4 / 255 (1.57%)	19 / 261 (7.28%)	8 / 239 (3.35%)
occurrences all number	10	5	19	8
Gastroenteritis
subjects affected / exposed	9 / 261 (3.45%)	6 / 255 (2.35%)	16 / 261 (6.13%)	9 / 239 (3.77%)
occurrences all number	10	6	23	9
Syphilis
subjects affected / exposed	4 / 261 (1.53%)	9 / 255 (3.53%)	13 / 261 (4.98%)	12 / 239 (5.02%)
occurrences all number	4	9	13	13
Sinusitis
subjects affected / exposed	9 / 261 (3.45%)	3 / 255 (1.18%)	15 / 261 (5.75%)	8 / 239 (3.35%)
occurrences all number	10	3	17	10
Respiratory tract infection
subjects affected / exposed	6 / 261 (2.30%)	3 / 255 (1.18%)	14 / 261 (5.36%)	4 / 239 (1.67%)
occurrences all number	8	5	16	5

More information

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Were there any global substantial amendments to the protocol? Yes

26 Feb 2015

Protocol was amended to include additional pharmacokinetic visits for the first 20 participants in the NNRTI subset who switch from efavirenz (EFV) or nevirapine (NVP) in the early switch phase and additional pharmacokinetic visits for all participants in the late switch phase, addition of stratification by planned participation in the DEXA substudy, revisions to inclusion and exclusion criteria, revision to the definition of study completion, edits to the time and events table, revisions to suicidal risk monitoring section, and minor clarifications and corrections of typographical errors.

08 Jun 2015

Protocol was amended to include reasons for switch for PI-class aligned with other ART class switches, revisions to stratified analysis of the primary endpoint, revisions to virologic withdrawal Criteria, references to study drug versus investigational product, and minor clarifications and corrections of typographical errors.Protocol was amended to include reasons for switch for PI-class aligned with other ART class switches, revisions to stratified analysis of the primary endpoint, revisions to virologic withdrawal Criteria, references to study drug versus investigational product, and minor clarifications and corrections of typographical errors.

27 Feb 2018

Protocol was amended to include: the introduction of commercially derived supplies of DTG as IP; included statements to clarify that in Taiwan and Russia, the Symptoms Distress Module is not utilized as no validated translations are available. Two editorial revisions were made to aid clarity and correct a typographical error.

03 Jul 2018

Changes were made to the protocol to manage and mitigate risks following identification of a potential safety issue related to neural tube defect in infants born to women with exposure to dolutegravir at the time of conception. The descriptions of the dolutegravir and rilpivirine Investigator’s Brochures were updated. The Risk Assessment table was updated to include language regarding risk and mitigation of neural tube defects. Inclusion criterion number 5 was updated to exclude the double barrier method of contraception, which does not meet updated GSK/ViiV criteria for a highly effective method. Acceptable methods of contraception were clarified. Withdrawal Criteria were updated to include a reminder that females of reproductive potential who change their minds and desire to be pregnant, or who state they are no longer willing to comply with the approved pregnancy avoidance methods should also be withdrawn from the study. The Time and Events Table was updated to include a reminder for investigators to check at every visit that females of reproductive potential are avoiding pregnancy. References was revised to update the references for the dolutegravir Investigator’s Brochure and the rilpivirine Investigator’s Brochure to the current versions, and to include a new reference citing methods of highly effective contraception.

10 Sep 2019

Changes were made to the protocol applicable only in the Russian Federation. This country-specific amendment was to facilitate treatment of participants recruited in the Russian Federation with the DTG/RPV fixed dose combination (FDC) tablet to satisfy a regulatory requirement for data of participants recruited locally who have received the DTG/RPV FDC. The reference section was updated to include the current versions of the dolutegravir Investigator’s Brochure and the rilpivirine Investigator’s Brochure.

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.

None reported

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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 plasma HIV-1 RNA <50 c/mL at Week 48 using snapshot algorithm

Primary: Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using snapshot algorithm

Secondary: Changes from Baseline in cluster designation (CD)4+ lymphocyte count at Weeks 24 and 48

Secondary: Changes from Baseline in cluster designation (CD)4+ lymphocyte count at Weeks 24 and 48

Secondary: Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 24 using snapshot algorithm

Secondary: Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 24 using snapshot algorithm

Secondary: Number of participants with common non-serious adverse event (AE), any serious AE (SAE), AE of maximum toxicity grade 1, 2, 3 or 4 and AE leading to discontinuation (AELD)

Secondary: Number of participants with common non-serious adverse event (AE), any serious AE (SAE), AE of maximum toxicity grade 1, 2, 3 or 4 and AE leading to discontinuation (AELD)

Secondary: Number of participants with maximum post-baseline emergent chemistry toxicities over 48 weeks

Secondary: Number of participants with maximum post-baseline emergent chemistry toxicities over 48 weeks

Secondary: Number of participants with maximum post-baseline emergent hematology toxicities over 48 weeks

Secondary: Number of participants with maximum post-baseline emergent hematology toxicities over 48 weeks

Secondary: Mean change from Baseline in high-sensitivity C-reactive protein (hs-CRP) at Week 48

Secondary: Mean change from Baseline in high-sensitivity C-reactive protein (hs-CRP) at Week 48

Secondary: Mean change from Baseline in cystatin C at Week 48

Secondary: Mean change from Baseline in cystatin C at Week 48

Secondary: Mean change from Baseline in D-Dimer at Week 48

Secondary: Mean change from Baseline in D-Dimer at Week 48

Secondary: Mean change from Baseline in fatty acid binding protein 2 (FABP) and soluble CD14 at Week 48

Secondary: Mean change from Baseline in fatty acid binding protein 2 (FABP) and soluble CD14 at Week 48

Secondary: Mean change from Baseline in Soluble CD163 and oxidized low density lipoprotein (LDL) at Week 48

Secondary: Mean change from Baseline in Soluble CD163 and oxidized low density lipoprotein (LDL) at Week 48

Secondary: Mean change from Baseline in retinol binding protein (RBP), serum creatinine and glucose at Week 48

Secondary: Mean change from Baseline in retinol binding protein (RBP), serum creatinine and glucose at Week 48

Secondary: Mean change from Baseline in urine phosphate at Week 48

Secondary: Mean change from Baseline in urine phosphate at Week 48

Secondary: Mean change from Baseline in beta-2-microglobulin (B2M) (blood and urine), urine RBP and 25 hydroxy-vitamin D (blood) at Week 48

Secondary: Mean change from Baseline in beta-2-microglobulin (B2M) (blood and urine), urine RBP and 25 hydroxy-vitamin D (blood) at Week 48

Secondary: Mean change from Baseline in urine albumin/creatinine ratio and urine protein/creatinine ratio at Week 48

Secondary: Mean change from Baseline in urine albumin/creatinine ratio and urine protein/creatinine ratio at Week 48

Secondary: Mean change from Baseline in bone-specific alkaline phosphatase, procollagen 1 N-terminal propeptide, osteocalcin, Type 1 Collagen C-telopeptides and soluble vascular cell adhesion molecule (sVCAM) at Week 48

Secondary: Mean change from Baseline in bone-specific alkaline phosphatase, procollagen 1 N-terminal propeptide, osteocalcin, Type 1 Collagen C-telopeptides and soluble vascular cell adhesion molecule (sVCAM) at Week 48

Secondary: Mean change from Baseline in interleukin 6 (IL-6) at Week 48

Secondary: Mean change from Baseline in interleukin 6 (IL-6) at Week 48

Secondary: Mean change from Baseline in insulin resistance based on homeostasis model assessment of insulin resistance (HOMA-IR) at Week 48

Secondary: Mean change from Baseline in insulin resistance based on homeostasis model assessment of insulin resistance (HOMA-IR) at Week 48

Secondary: Mean change from Baseline in fasting lipids at Weeks 24 and 48

Secondary: Mean change from Baseline in fasting lipids at Weeks 24 and 48

Secondary: Number of participants with genotypic resistance-Early switch Phase

Secondary: Number of participants with genotypic resistance-Early switch Phase

Secondary: Number of participants with genotypic resistance-DTG+RPV early switch group through Early and Late Switch Phase

Secondary: Number of participants with genotypic resistance-DTG+RPV early switch group through Early and Late Switch Phase

Secondary: Number of participants with genotypic resistance-CAR Late Switch Group through Late Switch Phase

Secondary: Number of participants with genotypic resistance-CAR Late Switch Group through Late Switch Phase

Secondary: Number of participants with phenotypic resistance-Early switch Phase

Secondary: Number of participants with phenotypic resistance-Early switch Phase

Secondary: Number of participants with phenotypic resistance-DTG+RPV early switch group through Early and Late Switch Phase

Secondary: Number of participants with phenotypic resistance-DTG+RPV early switch group through Early and Late Switch Phase

Secondary: Number of participants with phenotypic resistance-CAR Late Switch Group through Late Switch Phase

Secondary: Number of participants with phenotypic resistance-CAR Late Switch Group through Late Switch Phase

Secondary: Pre-dose concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 in participants switching to DTG + RPV-DTG+RPV early switch group through Early and Late Switch Phase

Secondary: Pre-dose concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 in participants switching to DTG + RPV-DTG+RPV early switch group through Early and Late Switch Phase

Secondary: Pre-dose concentrations of DTG and RPV at Weeks 56, 76 and 100 in participants switching to DTG + RPV-CAR Late Switch Group through Late Switch Phase

Secondary: Pre-dose concentrations of DTG and RPV at Weeks 56, 76 and 100 in participants switching to DTG + RPV-CAR Late Switch Group through Late Switch Phase

Secondary: Pre-dose concentrations of DTG and RPV at Weeks 2, 4 and 8 in the first 20 participants who switch from efavirenz (EFV) or nevirapine (NVP) to DTG + RPV

Secondary: Pre-dose concentrations of DTG and RPV at Weeks 2, 4 and 8 in the first 20 participants who switch from efavirenz (EFV) or nevirapine (NVP) to DTG + RPV

Secondary: Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 48 using snapshot algorithm by Baseline third agent treatment class

Secondary: Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 48 using snapshot algorithm by Baseline third agent treatment class

Secondary: Changes from Baseline in CD4+ lymphocyte count at Week 48 by Baseline third agent treatment class

Secondary: Changes from Baseline in CD4+ lymphocyte count at Week 48 by Baseline third agent treatment class

Secondary: Number of participants with any AE, AELD or AE with grade 1, 2, 3 or 4 toxicity over 48 weeks by Baseline third agent treatment class

Secondary: Number of participants with any AE, AELD or AE with grade 1, 2, 3 or 4 toxicity over 48 weeks by Baseline third agent treatment class

Secondary: Number of participants with maximum post-baseline emergent chemistry toxicities over 48 weeks by Baseline third agent treatment class

Secondary: Number of participants with maximum post-baseline emergent chemistry toxicities over 48 weeks by Baseline third agent treatment class

Secondary: Number of participants with maximum post-baseline emergent hematology toxicities over 48 weeks by Baseline third agent treatment class

Secondary: Number of participants with maximum post-baseline emergent hematology toxicities over 48 weeks by Baseline third agent treatment class

Secondary: Number of participants with observed genotypic resistance for participants meeting virologic withdrawal criteria by Baseline third agent treatment class

Secondary: Number of participants with observed genotypic resistance for participants meeting virologic withdrawal criteria by Baseline third agent treatment class

Secondary: Number of participants with observed phenotypic resistance for participants meeting virologic withdrawal criteria by Baseline third agent treatment class

Secondary: Number of participants with observed phenotypic resistance for participants meeting virologic withdrawal criteria by Baseline third agent treatment class

Secondary: Change from Baseline in fasting lipids at Weeks 24 and 48 by Baseline third agent treatment class