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Clinical Trial Results:
A Phase III, randomised, double-blind, multicentre, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of dolutegravir plus lamivudine compared to dolutegravir plus tenofovir/emtricitabine in HIV-1-infected treatment-naïve adults

Summary
EudraCT number	2016-000459-28
Trial protocol	DE BE PT ES FR IT
Global end of trial date

Results information
Results version number	v1
This version publication date	13 Apr 2019
First version publication date	13 Apr 2019
Other versions	v2 , v3

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

205543

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, ViiV Healthcare, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, ViiV Healthcare, 1 8664357343, GSKClinicalSupportHD@gsk.com

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

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

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

Analysis stage

Interim

Date of interim/final analysis

09 Jul 2018

Is this the analysis of the primary completion data?

Yes

Primary completion date

04 Apr 2018

Global end of trial reached?

Main objective of the trial

To demonstrate non-inferior antiviral activity of DTG + 3TC versus DTG + TDF/FTC at 48 weeks in HIV-1-infected, ART-naïve participants

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Jul 2016

Long term follow-up planned

Yes

Long term follow-up rationale

Ethical reason

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

Argentina: 77

Country: Number of subjects enrolled

Australia: 14

Country: Number of subjects enrolled

Belgium: 8

Country: Number of subjects enrolled

Canada: 13

Country: Number of subjects enrolled

France: 10

Country: Number of subjects enrolled

Germany: 16

Country: Number of subjects enrolled

Italy: 52

Country: Number of subjects enrolled

Mexico: 43

Country: Number of subjects enrolled

Peru: 23

Country: Number of subjects enrolled

Poland: 9

Country: Number of subjects enrolled

Portugal: 20

Country: Number of subjects enrolled

Romania: 21

Country: Number of subjects enrolled

Russian Federation: 87

Country: Number of subjects enrolled

Spain: 98

Country: Number of subjects enrolled

Switzerland: 13

Country: Number of subjects enrolled

Taiwan: 55

Country: Number of subjects enrolled

United States: 135

Country: Number of subjects enrolled

United Kingdom: 28

Worldwide total number of subjects

722

EEA total number of subjects

262

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)

719

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study is a Phase 3, randomized, double-blind, parallel group, non-inferiority study. A total of 104 investigational centers in 18 countries randomized one or more participants in this multicenter study. The results presented are based on the primary analysis at Week 48.

Screening details

Total of 722 participants were enrolled and randomized; however only 719 participants (3 participants were never dosed following randomization as they withdrew consent to participate in study) were dosed in to the study to receive either dolutegravir plus lamivudine (DTG+3TC) or dolutegravir plus tenofovir/emtricitabine (DTG+TDF/FTC).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor

Are arms mutually exclusive

Yes

DTG + 3TC

Arm description

Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.

Arm type

Experimental

Investigational medicinal product name

Dolutegravir (DTG)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

DTG 50 mg tablet, oral administration, once daily.

Investigational medicinal product name

Lamivudine (3TC)

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

3TC 300 mg capsule, oral administration, once daily.

DTG + TDF/FTC

Arm description

Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.

Arm type

Active comparator

Investigational medicinal product name

Dolutegravir (DTG)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

DTG 50 mg tablet, oral administration, once daily.

Investigational medicinal product name

Tenofovir disoproxil fumarate/emtricitabine fixed-dose combination (TDF/FTC)

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

300 mg TDF/ 200 mg FTC capsule, oral administration, once daily.

Number of subjects in period 1 ^[1]	DTG + 3TC	DTG + TDF/FTC
Started	360	359
Completed	0	0
Not completed	360	359
Adverse event, serious fatal	2	-
Consent withdrawn by subject	7	6
Physician decision	2	2
Adverse event, non-fatal	6	5
Protocol specific withdrawal criteria	-	2
Ongoing at the time of the analysis	330	335
Lost to follow-up	6	5
Lack of efficacy	2	2
Protocol deviation	5	2

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 of 722 participants were enrolled and randomized however only 719 participants (3 participants were never dosed following randomization as they withdrew consent to participate in study) were dosed in to the study to receive either dolutegravir plus lamivudine (DTG+3TC) or dolutegravir plus tenofovir/emtricitabine (DTG+TDF/FTC).

Baseline characteristics

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Reporting group title

DTG + 3TC

Reporting group description

Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.

Reporting group title

DTG + TDF/FTC

Reporting group description

Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.

Reporting group values	DTG + 3TC	DTG + TDF/FTC	Total
Number of subjects	360	359	719
Age categorical
Units: Subjects
Overall number of baseline subjects	360	359	719
Age Continuous
Units: Years
arithmetic mean (standard deviation)	34.6 ( 10.72 )	34.4 ( 10.35 )	-
Sex: Female, Male
Units: Subjects
Female	54	46	100
Male	306	313	619
Race/Ethnicity, Customized
Units: Subjects
American (Am) Indian or Alaska (Al.) native	21	24	45
Asian-Central/South Asian heritage (H.)	0	3	3
Asian - East Asian H.	28	26	54
Asian - South East Asian H.	6	1	7
Black or African Am	55	40	95
Native Hawaiian or other Pacific Islander	0	5	5
White (Wt)-Arabic/North African H.	3	3	6
Wt-Wt/Caucasian (Ca.)/European (Eu.) H.	234	246	480
Am Indian or Al. native and Wt	12	10	22
Black or African Am and Wt	1	1	2

End points

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Reporting group title

DTG + 3TC

Reporting group description

Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.

Reporting group title

DTG + TDF/FTC

Reporting group description

Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.

Primary: Percentage of participants with plasma Human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL (c/mL) at Week 48

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End point title

Percentage of participants with plasma Human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL (c/mL) at Week 48

End point description

Percentage of participants with HIV-1 RNA<50 c/mL was obtained using Food and Drug Administration (FDA) Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of invetigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel (CMH) weights. Intent-To-Treat Exposed (ITT-E) Population was used which comprised of all randomized participants who receive at least one dose of study treatment.

End point type

Primary

End point timeframe

Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[1]	359 ^[2]
Units: Percentage of participants
number (confidence interval 95%)	93 (90.4 to 95.7)	94 (91.4 to 96.4)

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

Stat 1

Statistical analysis description

Difference in proportion was based on CMH stratified analysis adjusting for Baseline stratification factors: Plasma HIV-1 RNA (<= vs. >100,000 copies per milliliter) and CD4+ cell count (<= vs. >200 cells per cubic millimeter [cells/mm^3].

Comparison groups

DTG + TDF/FTC v DTG + 3TC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Adjusted difference in proportion

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.3

upper limit

2.9

Notes
[3] - Treatment with DTG+ 3TC was to be declared non-inferior to treatment with DTG+TDF/FTC if the lower end of a two-sided 95% confidence interval for the difference between the two groups in response rates at Week 48 was greater than -10%.

Secondary: Percentage of participants with plasma HIV-1 RNA <50 c/mL at Weeks 24

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End point title

Percentage of participants with plasma HIV-1 RNA <50 c/mL at Weeks 24

End point description

Percentage of participants with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. This endpoint was analyzed using a stratified analysis with CMH weights.

End point type

Secondary

End point timeframe

Week 24

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[4]	359 ^[5]
Units: Percentage of participants
number (confidence interval 95%)	94 (91.4 to 96.4)	94 (91.4 to 96.4)

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

Stat 1

Statistical analysis description

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

^[6]

Method

Parameter type

Adjusted difference in proportion

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.6

Notes
[6] - Treatment with DTG+ 3TC was to be declared non-inferior to treatment with DTG+TDF/FTC if the lower end of a two-sided 95% confidence interval for the difference between the two groups in response rates at Week 48 was greater than -10%.

Secondary: Time to viral suppression (HIV-1 RNA <50 c/mL)

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End point title

Time to viral suppression (HIV-1 RNA <50 c/mL)

End point description

Time of viral suppression is defined as the first viral load value <50 c/mL. Nonparametric Kaplan-Meier method was performed. Participants who withdrew for any reason without being suppressed were censored at date of withdrawal. Participants who have not been withdrawn and have not had viral suppression at time of the analysis were censored at last viral load date. Confidence Interval (CI) was estimated using the Brookmeyer-Crowley method. Median along with first Quartile and third Quartile have been presented.

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[7]	359 ^[8]
Units: Days
median (inter-quartile range (Q1-Q3))	29.0 (29.0 to 55.0)	29.0 (29.0 to 57.0)

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

Stat 1

Statistical analysis description

Hazard ratios were estimated using the Cox proportional hazard regression model.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.825 ^[9]

Method

Generalised Wilcoxon procedure

Parameter type

Hazard ratio (HR)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.18

Notes
[9] - The generalised Wilcoxon procedure was used to estimate a p-value for detecting a difference in cumulative incidence curves between treatment groups.

Secondary: CD4+ cell counts at Weeks 24 and 48

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End point title

CD4+ cell counts at Weeks 24 and 48

End point description

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+ cells. Analysis was performed by flow cytometry. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Weeks 24 and 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[10]	359 ^[11]
Units: Cells/mm^3
arithmetic mean (standard deviation)
Week 24, n=349,345	650.4 ( 257.02 )	633.0 ( 287.37 )
Week 48, n=337,340	688.1 ( 266.39 )	689.8 ( 308.49 )

Notes
[10] - ITT-E Population
[11] - ITT-E Population

No statistical analyses for this end point

Secondary: Changes from Baseline in CD4+ cell counts at Week 24 and 48

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End point title

Changes from Baseline in CD4+ cell counts at Week 24 and 48

End point description

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+ cells. Analysis was performed by flow cytometry. Baseline value is defined as the the latest pre-dose assessment. Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted least mean and standard error has been presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for the following covariates/factors: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction, and Baseline CD4+ cell count and visit interaction, with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[12]	359 ^[13]
Units: Cells/mm^3
least squares mean (standard error)
Week 24, n=349, 345	188.8 ( 8.77 )	163.2 ( 9.08 )
Week 48, n=337, 340	225.7 ( 8.94 )	217.2 ( 9.93 )

Notes
[12] - ITT-E Population
[13] - ITT-E Population

Stat 1

Statistical analysis description

Week 24. Following covariates/factors were adjusted: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction and Baseline CD4+ cell count and visit interaction with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.043

Method

Mixed Model Repeated Measures (MMRM)

Parameter type

Mean difference (net)

Point estimate

25.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

50.4

Stat 2

Statistical analysis description

Week 48. Following covariates/factors were adjusted: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction and Baseline CD4+ cell count and visit interaction with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.523

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

8.5

Confidence interval

level

95%

sides

2-sided

lower limit

-17.7

upper limit

34.8

Secondary: Number of participants with HIV-1 Disease Progression

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End point title

Number of participants with HIV-1 Disease Progression

End point description

HIV-associated conditions were recorded during the study and was assessed according to the 2014 Centers for Disease Control and Prevention (CDC) Classification System for HIV Infection in Adults. Disease progressions summarize participants who had HIV infection stage 3 associated conditions or death. Indicators of clinical disease progression were defined as: CDC Category Stage 1 at enrollment to Stage 3 event; CDC Category Stage 2 at enrolment to Stage 3 event; CDC Category Stage 3 at enrolment to New Stage 3 Event; CDC Category Stage 1, 2 or 3 at enrollment to Death.

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[14]	359 ^[15]
Units: Participants
No disease progression	356	358
From CDC Stage 1 to CDC Stage 3 Event	0	0
From CDC Stage 2 to CDC Stage 3 Event	1	1
From CDC Stage 3 to New CDC Stage 3 Event	1	0
From CDC Stage 1, 2 or 3 to Death	2	0

Notes
[14] - ITT-E Population
[15] - ITT-E Population

No statistical analyses for this end point

Secondary: Number of participants with treatment-emergent genotypic resistance

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End point title

Number of participants with treatment-emergent genotypic resistance

End point description

Number of participants, who meet confirmed virologic withdrawal (CVW) criteria, with treatment emergent genotypic resistance to Integrase strand transfer inhibitor (INSTI) and/or Nucleoside reverse transcriptase inhibitor (NRTI) was summarized. The Viral Genotypic Population comprised of all participants in the ITT-E population who have available on-treatment genotypic resistance data.

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	2 ^[16]	2 ^[17]
Units: Participants
INSTI Mutations	0	0
Major mutations of the NRTI	0	0

Notes
[16] - Viral Genotypic Population
[17] - Viral Genotypic Population

No statistical analyses for this end point

Secondary: Number of participants with treatment-emergent phenotypic resistance

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End point title

Number of participants with treatment-emergent phenotypic resistance

End point description

Number of participants, who meet CVW criteria, with treatment emergent phenotypic resistance to INSTI and/or NRTI were summarized. Assessment of antiviral activity of anti-retroviral therapy (ART) using phenotypic test results were interpreted through a proprietary algorithm (from Monogram Biosciences) and provides the overall susceptibility of the drugs (Abacavir [ABC], elvitegravir [EGV], raltegravir [RAL], zidovudine [AZT], stavudine [D4T], didanosine [DDI]), emtricitabine [FTC], tenofovir disiproxil fumarate [TDF]). Partially sensitive and resistant cells were considered resistant in this analysis. Number of participants with phenotype at time of CVW by phenotypic cut-off at or prior to Week 48 have been presented. The Viral Phenotypic Population comprised of all participants in the ITT-E population who have available on-treatment phenotypic resistance data. Only those participants 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 + 3TC	DTG + TDF/FTC
Number of subjects analysed	2 ^[18]	2 ^[19]
Units: Participants
INSTI, DTG, Sensitive, n=2,1	2	1
INSTI, DTG, Resistant, n=2,1	0	0
INSTI, EVG, Sensitive, n=2,1	2	1
INSTI, EVG, Resistant, n=2,1	0	0
INSTI, RAL, Sensitive, n=2,1	2	1
INSTI, RAL, Resistant, n=2,1	0	0
NRTI, 3TC, Sensitive, n=2,2	2	2
NRTI, 3TC, Resistant, n=2,2	0	0
NRTI, ABC, Sensitive, n=2,2	2	2
NRTI, ABC, Resistant, n=2,2	0	0
NRTI, AZT, Sensitive, n=2,2	2	2
NRTI, AZT, Resistant, n=2,2	0	0
NRTI, D4T, Sensitive, n=2,2	2	2
NRTI, D4T, Resistant, n=2,2	0	0
NRTI, DDI, Sensitive, n=2,2	2	2
NRTI, DDI, Resistant, n=2,2	0	0
NRTI, FTC, Sensitive, n=2,2	2	2
NRTI, FTC, Resistant, n=2,2	0	0
NRTI, TDF, Sensitive, n=2,2	2	2
NRTI, TDF, Resistant, n=2,2	0	0

Notes
[18] - Viral Phenotypic Population
[19] - Viral Phenotypic Population

No statistical analyses for this end point

Secondary: Number of participants with any adverse event (AE) and serious AE (SAE)

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End point title

Number of participants with any adverse event (AE) and serious AE (SAE)

End point description

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the 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 or event associated with liver injury and impaired liver function were categorized as SAE. Safety Population was used which comprised of all participants who received at least one dose of study treatment Analyses presented herein used a data cut-off date of 22 May 2018 (for Week 48 database freeze), i.e. may include data collected after a participant’s Week 48 visit..

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[20]	359 ^[21]
Units: Participants
Any AE	267	284
Any SAE	29	33

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

No statistical analyses for this end point

Secondary: Number of participants with AEs by maximum severity grades

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End point title

Number of participants with AEs by maximum severity grades

End point description

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented. Analyses presented herein used a data cut-off date of 22 May 2018 (for Week 48 database freeze), i.e. may include data collected after a participant’s Week 48 visit.

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[22]	359 ^[23]
Units: Participants
Grade 1 AEs	79	93
Grade 2 AEs	161	159
Grade 3 AEs	19	29
Grade 4 AEs	6	3
Grade 5 AEs	2	0

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

No statistical analyses for this end point

Secondary: Number of participants with any drug related AEs and drug related AEs by maximum grade

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End point title

Number of participants with any drug related AEs and drug related AEs by maximum grade

End point description

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the DAIDS toxicity scales from Grade 1 to 5. (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with drug related AEs and drug related AEs by by maximum grade have been presented. Analyses presented herein used a data cut-off date of 22 May 2018 (for Week 48 database freeze), i.e. may include data collected after a participant’s Week 48 visit.

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[24]	359 ^[25]
Units: Participants
Any drug related AE	55	75
Drug related AEs with maximum toxicity Grade 1	34	53
Drug related AEs with maximum toxicity Grade 2	17	17
Drug related AEs with maximum toxicity Grade 3	3	4
Drug related AEs with maximum toxicity Grade 4	1	1
Drug related AEs with maximum toxicity Grade 5	0	0

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

No statistical analyses for this end point

Secondary: Number of participants with maximum post-Baseline emergent hematology toxicities

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End point title

Number of participants with maximum post-Baseline emergent hematology toxicities

End point description

Blood samples were collected up to Week 48 for assessment of platelet count, neutrophils, hemoglobin, and Leukocytes. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Only those participants with maximum post-Baseline emergent hematology toxicities in any of the listed hematology parameters have been presented.

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[26]	359 ^[27]
Units: Participants
Hemoglobin, Grades 1 to 4	8	7
Hemoglobin, Grades 2 to 4	5	4
Hemoglobin, Grades 3 to 4	2	1
Hemoglobin, Grade 1	3	3
Hemoglobin, Grade 2	3	3
Hemoglobin, Grade 3	1	1
Hemoglobin, Grade 4	1	0
Leukocytes, Grades 1 to 4	4	3
Leukocytes, Grades 2 to 4	1	0
Leukocytes, Grades 3 to 4	0	0
Leukocytes, Grade 1	3	3
Leukocytes, Grade 2	1	0
Leukocytes, Grade 3	0	0
Leukocytes, Grade 4	0	0
Neutrophils, Grades 1 to 4	14	6
Neutrophils, Grades 2 to 4	4	2
Neutrophils, Grades 3 to 4	1	1
Neutrophils, Grade 1	10	4
Neutrophils, Grade 2	3	1
Neutrophils, Grade 3	1	1
Neutrophils, Grade 4	0	0
Platelets, Grades 1 to 4	11	9
Platelets, Grades 2 to 4	5	5
Platelets, Grades 3 to 4	0	0
Platelets, Grade 1	6	4
Platelets, Grade 2	5	5
Platelets, Grade 3	0	0
Platelets, Grade 4	0	0

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

No statistical analyses for this end point

Secondary: Number of participants with maximum post-Baseline emergent chemistry toxicities

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End point title

Number of participants with maximum post-Baseline emergent chemistry toxicities

End point description

Blood samples were collected up to Week 48 for assessment of Alanine Aminotransferase (ALT), Aspartate aminotransferase (AST), Albumin, Alkaline Phosphatase (ALP), Bilirubin, Carbon dioxide (CO2), Cholesterol, Creatine kinase (CPK), Creatinine, Direct Bilirubin, Glomerular filtration rate (GFR), Hypercalcemia, Hyperglycemia, Hyperkalemia, Hypernatremia, Hypocalcemia, Hypoglycemia, Hypokalemia and Hyponatremia, Low density lipid (LDL) Cholesterol, Lactate Dehydrogenase, Lipase and Phosphate. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Only those participants with maximum post-Baseline emergent chemistry toxicities in any of the chemistry parameters have been presented.

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[28]	359 ^[29]
Units: Participants
ALT, Grades 1 to 4	43	51
ALT, Grades 2 to 4	17	22
ALT, Grades 3 to 4	9	10
ALT, Grade 1	26	29
ALT, Grade 2	8	12
ALT, Grade 3	4	4
ALT, Grade 4	5	6
Albumin, Grades 1 to 4	0	1
Albumin, Grades 2 to 4	0	1
Albumin, Grades 3 to 4	0	1
Albumin, Grade 1	0	0
Albumin, Grade 2	0	0
Albumin, Grade 3	0	1
Albumin, Grade 4	0	0
ALP, Grades 1 to 4	6	14
ALP, Grades 2 to 4	2	3
ALP, Grades 3 to 4	0	1
ALP, Grade 1	4	11
ALP, Grade 2	2	2
ALP, Grade 3	0	1
ALP, Grade 4	0	0
AST, Grades 1 to 4	42	56
AST, Grades 2 to 4	17	23
AST, Grades 3 to 4	7	12
AST, Grade 1	25	33
AST, Grade 2	10	11
AST, Grade 3	3	9
AST, Grade 4	4	3
Bilirubin, Grades 1 to 4	33	38
Bilirubin, Grades 2 to 4	8	11
Bilirubin, Grades 3 to 4	3	3
Bilirubin, Grade 1	25	27
Bilirubin, Grade 2	5	8
Bilirubin, Grade 3	0	2
Bilirubin, Grade 4	3	1
CO2, Grades 1 to 4	71	87
CO2, Grades 2 to 4	6	2
CO2, Grades 3 to 4	0	0
CO2, Grade 1	65	85
CO2, Grade 2	6	2
CO2, Grade 3	0	0
CO2, Grade 4	0	0
Cholesterol, Grades 1 to 4	70	26
Cholesterol, Grades 2 to 4	11	5
Cholesterol, Grades 3 to 4	0	0
Cholesterol, Grade 1	59	21
Cholesterol, Grade 2	11	5
Cholesterol, Grade 3	0	0
Cholesterol, Grade 4	0	0
CK, Grades 1 to 4	61	48
CK, Grades 2 to 4	34	28
CK, Grades 3 to 4	19	17
CK, Grade 1	27	20
CK, Grade 2	15	11
CK, Grade 3	9	6
CK, Grade 4	10	11
Creatinine, Grades 1 to 4	14	19
Creatinine, Grades 2 to 4	3	2
Creatinine, Grades 3 to 4	0	1
Creatinine, Grade 1	11	17
Creatinine, Grade 2	3	1
Creatinine, Grade 3	0	1
Creatinine, Grade 4	0	0
Direct Bilirubin, Grades 1 to 4	7	7
Direct Bilirubin, Grades 2 to 4	7	7
Direct Bilirubin, Grades 3 to 4	7	7
Direct Bilirubin, Grade 1	0	0
Direct Bilirubin, Grade 2	0	0
Direct Bilirubin, Grade 3	7	7
Direct Bilirubin, Grade 4	0	0
GFR, Grades 1 to 4	154	190
GFR, Grades 2 to 4	154	190
GFR, Grades 3 to 4	13	18
GFR, Grade 1	0	0
GFR, Grade 2	141	172
GFR, Grade 3	13	17
GFR, Grade 4	0	1
Hypercalcaemia, Grades 1 to 4	3	5
Hypercalcaemia, Grades 2 to 4	0	1
Hypercalcaemia, Grades 3 to 4	0	1
Hypercalcemia, Grade 1	3	4
Hypercalcaemia, Grade 2	0	0
Hypercalcaemia, Grade 3	0	0
Hypercalcaemia, Grade 4	0	1
Hyperglycaemia, Grades 1 to 4	74	57
Hyperglycaemia, Grades 2 to 4	30	21
Hyperglycaemia, Grades 3 to 4	2	3
Hyperglycaemia, Grade 1	44	36
Hyperglycaemia, Grade 2	28	18
Hyperglycaemia, Grade 3	2	2
Hyperglycaemia, Grade 4	0	1
Hyperkalemia, Grades 1 to 4	4	4
Hyperkalemia, Grades 2 to 4	1	0
Hyperkalemia, Grades 3 to 4	0	0
Hyperkalemia, Grade 1	3	4
Hyperkalemia, Grade 2	1	0
Hyperkalemia, Grade 3	0	0
Hyperkalemia, Grade 4	0	0
Hypernatremia, Grades 1 to 4	1	5
Hypernatremia, Grades 2 to 4	0	0
Hypernatremia, Grades 3 to 4	0	0
Hypernatremia, Grade 1	1	5
Hypernatremia, Grade 2	0	0
Hypernatremia, Grade 3	0	0
Hypernatremia, Grade 4	0	0
Hypocalcaemia, Grades 1 to 4	7	10
Hypocalcaemia, Grades 2 to 4	1	5
Hypocalcaemia, Grades 3 to 4	0	1
Hypocalcaemia, Grade 1	6	5
Hypocalcaemia, Grade 2	1	4
Hypocalcaemia, Grade 3	0	1
Hypocalcaemia, Grade 4	0	0
Hypoglycaemia, Grades 1 to 4	13	13
Hypoglycaemia, Grades 2 to 4	4	4
Hypoglycaemia, Grades 3 to 4	3	1
Hypoglycaemia, Grade 1	9	9
Hypoglycaemia, Grade 2	1	3
Hypoglycaemia, Grade 3	2	0
Hypoglycaemia, Grade 4	1	1
Hypokalemia, Grades 1 to 4	3	0
Hypokalemia, Grades 2 to 4	0	0
Hypokalemia, Grades 3 to 4	0	0
Hypokalemia, Grade 1	3	0
Hypokalemia, Grade 2	0	0
Hypokalemia, Grade 3	0	0
Hypokalemia, Grade 4	0	0
Hyponatremia, Grades 1 to 4	14	18
Hyponatremia, Grades 2 to 4	0	2
Hyponatremia, Grades 3 to 4	0	0
Hyponatremia, Grade 1	14	16
Hyponatremia, Grade 2	0	2
Hyponatremia, Grade 3	0	0
Hyponatremia, Grade 4	0	0
LDL Cholesterol, Grades 1 to 4	48	22
LDL Cholesterol, Grades 2 to 4	14	5
LDL Cholesterol, Grades 3 to 4	3	0
LDL Cholesterol, Grade 1	34	17
LDL Cholesterol, Grade 2	11	5
LDL Cholesterol, Grade 3	3	0
LDL Cholesterol, Grade 4	0	0
Lactate Dehydrogenase, Grades 1 to 4	3	2
Lactate Dehydrogenase, Grades 2 to 4	3	0
Lactate Dehydrogenase, Grades 3 to 4	0	0
Lactate Dehydrogenase, Grade 1	0	2
Lactate Dehydrogenase, Grade 2	3	0
Lactate Dehydrogenase, Grade 3	0	0
Lactate Dehydrogenase, Grade 4	0	0
Lipase, Grades 1 to 4	48	60
Lipase, Grades 2 to 4	21	28
Lipase, Grades 3 to 4	2	10
Lipase, Grade 1	27	32
Lipase, Grade 2	19	18
Lipase, Grade 3	0	9
Lipase, Grade 4	2	1
Phosphate, Grades 1 to 4	53	51
Phosphate, Grades 2 to 4	31	33
Phosphate, Grades 3 to 4	2	4
Phosphate, Grade 1	22	18
Phosphate, Grade 2	29	29
Phosphate, Grade 3	2	4
Phosphate, Grade 4	0	0
Triglycerides, Grades 1 to 4	58	52
Triglycerides, Grades 2 to 4	11	7
Triglycerides, Grades 3 to 4	3	1
Triglycerides, Grade 1	47	45
Triglycerides, Grade 2	8	6
Triglycerides, Grade 3	3	1
Triglycerides, Grade 4	0	0

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

No statistical analyses for this end point

Secondary: Number of participants who discontinue treatment due to AEs over Weeks 24, 48

Top of page

End point title

Number of participants who discontinue treatment due to AEs over Weeks 24, 48

End point description

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants who discontinued treatment due to AEs have been reported. Analyses presented herein used a data cut-off date of 19 January 2018 and 22 May 2018, respectively, for the Week 24 database freeze and Week 48 database freeze), i.e. may include data collected after a participant’s Week 24 or 48 visit, respectively.

End point type

Secondary

End point timeframe

Weeks 24 and 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[30]	359 ^[31]
Units: Participants
Up to Week 24	6	4
Up to Week 48	8	8

Notes
[30] - Safety Population
[31] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in renal biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48

Top of page

End point title

Change from Baseline in renal biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48

End point description

Blood and/or urine samples were collected to perform evaluation of renal inflammation biomarkers which included Serum Cystatin C and Serum Retinol Binding Protein (RBP). Baseline value is the the latest pre-dose assessment. Change from Baseline was defined as value at indicated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and at Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[32]	359 ^[33]
Units: Milligrams per Liter (mg/L)
least squares mean (standard error)
Serum Cystatin C, Week 24, n=345,345	-0.04 ( 0.005 )	0.00 ( 0.005 )
Serum Cystatin C, Week 48, n=335,336	-0.05 ( 0.005 )	-0.04 ( 0.006 )
Serum RBP, Week 24, n=345,343	1.2 ( 0.42 )	1.4 ( 0.48 )
Serum RBP, Week 48, n=334, 334	0.6 ( 0.45 )	-0.1 ( 0.42 )

Notes
[32] - Safety Population
[33] - Safety Population

Stat 1

Statistical analysis description

Week 24. Serum Cystatin C.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

-0.02

Stat 2

Statistical analysis description

Week 48. Serum Cystatin C.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.022

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

Stat 3

Statistical analysis description

Week 24. Serum RBP.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.797

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

1.1

Stat 4

Statistical analysis description

Week 48. Serum RBP.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.258

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

1.9

Secondary: Change from Baseline in renal biomarkers-Serum GFR from cystatin C Adjusted using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR from creatinine adjusted using CKD-EPI at Weeks 24, 48

Top of page

End point title

Change from Baseline in renal biomarkers-Serum GFR from cystatin C Adjusted using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR from creatinine adjusted using CKD-EPI at Weeks 24, 48

End point description

Blood samples were collected to perform evaluation of renal inflammation biomarkers which included Serum GFR from cystatin C adjusted using CKD-EPI (GFR-cystatin C adjusted) and Serum or Plasma GFR from creatinine adjusted using CKD-EPI. Baseline value is the latest pre-dose Assessment. Change from Baseline was defined as value at the indicated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and at Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[34]	359 ^[35]
Units: Milliliter/minute/1.73 meter^2
arithmetic mean (standard error)
GFR Cystatin C adjusted, Week 24, n=345,345	3.8 ( 0.66 )	0.2 ( 0.65 )
GFR Cystatin C adjusted, Week 48, n=335,336	5.4 ( 0.64 )	3.6 ( 0.64 )
GFR creatinine adjusted, Week 24, n=346,344	-12.0 ( 0.64 )	-15.4 ( 0.59 )
GFR creatinine adjusted, Week 48, n=335, 337	-12.1 ( 0.60 )	-15.4 ( 0.61 )

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

Stat 1

Statistical analysis description

Week 24. GFR Cystatin C adjusted.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.8

upper limit

5.4

Stat 2

Statistical analysis description

Week 48. GFR Cystatin C adjusted.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.056

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

3.5

Stat 3

Statistical analysis description

Week 24. GFR creatinine adjusted

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.7

upper limit

5.2

Stat 4

Statistical analysis description

Week 48. GFR creatinine adjusted.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.3

Confidence interval

level

95%

sides

2-sided

lower limit

1.6

upper limit

Secondary: Change from Baseline in renal biomarker-Serum or Plasma Creatinine at Weeks 24, 48

Top of page

End point title

Change from Baseline in renal biomarker-Serum or Plasma Creatinine at Weeks 24, 48

End point description

Blood and samples were collected to perform evaluation of renal inflammation biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the the latest pre-dose assessment. Change from Baseline was calculated as value at the inidcated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and at Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[36]	359 ^[37]
Units: Micromoles per Liter (umol/L)
arithmetic mean (standard deviation)
Serum or Plasma Creatinine, Week 24, n=346, 344	10.51 ( 0.548 )	13.53 ( 0.507 )
Serum or Plasma Creatinine, Week 48, n=335, 337	10.32 ( 0.519 )	13.44 ( 0.540 )

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

Stat 1

Statistical analysis description

Week 24. Serum Plasma Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.02

Confidence interval

level

95%

sides

2-sided

lower limit

-4.49

upper limit

-1.55

Stat 2

Statistical analysis description

Week 48. Serum Plasma creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.12

Confidence interval

level

95%

sides

2-sided

lower limit

-4.59

upper limit

-1.65

Secondary: Ratio to Baseline in renal biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48

Top of page

End point title

Ratio to Baseline in renal biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48

End point description

Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers: Urine and Serum B2M, Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine. Baseline value was the latest pre-dose assessment. Change from Baseline was performed on log-transformed data. Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Geometric mean ratio and 95% CI of geometric mean ratio have been presented. Biomarkers were Adjusted for treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, loge transformed Baseline biomarker value, treatment and visit interaction, and loge transformed Baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[38]	359 ^[39]
Units: Ratio
geometric mean (confidence interval 95%)
Serum B2M, Week 24, n=344,346	0.809 (0.794 to 0.824)	0.882 (0.867 to 0.898)
Serum B2M, Week 48, n=335,336	0.811 (0.796 to 0.827)	0.887 (0.871 to 0.904)
Urine B2M, Week 24, n=124,106	0.844 (0.755 to 0.944)	1.129 (0.974 to 1.309)
Urine B2M, Week 48, n=109, 103	0.917 (0.804 to 1.046)	1.323 (1.066 to 1.642)
Urine Albumin/Creatinine, Week 24, n=259, 251	0.907 (0.844 to 0.976)	1.021 (0.940 to 1.109)
Urine Albumin/Creatinine , Week 48, n=249, 240	0.911 (0.835 to 0.994)	0.971 (0.891 to 1.058)
Urine B2M/Urine Creatinine , Week 24, n=122, 104	0.880 (0.779 to 0.993)	1.126 (0.988 to 1.282)
Urine B2M/Urine Creatinine , Week 48, n=108, 103	0.969 (0.854 to 1.099)	1.307 (1.077 to 1.586)
Urine Phosphate, Week 24, n=343, 340	1.041 (0.955 to 1.134)	1.063 (0.978 to 1.157)
Urine Phosphate , Week 48, n=335, 332	1.121 (1.031 to 1.220)	1.056 (0.974 to 1.144)
Urine Protein/Creatinine , Week 24, n=263,279	0.818 (0.779 to 0.859)	0.991 (0.941 to 1.043)
Urine Protein/Creatinine , Week 48, n=259, 261	0.866 (0.818 to 0.917)	1.007 (0.954 to 1.062)
Urine RBP 4, Week 24, n=340, 338	0.656 (0.591 to 0.729)	0.824 (0.738 to 0.921)
Urine RBP 4, Week 48, n=333, 331	0.740 (0.666 to 0.822)	0.819 (0.730 to 0.919)
Urine RBP 4/Urine Creatinine , Week 24, n=338, 335	0.670 (0.614 to 0.730)	0.811 (0.741 to 0.888)
Urine RBP 4/Urine Creatinine , Week 48, n=331, 328	0.749 (0.689 to 0.814)	0.844 (0.774 to 0.920)

Notes
[38] - Safety Population
[39] - Safety Population

Stat 1

Statistical analysis description

Week 24. Serum B2M.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.917

Confidence interval

level

95%

sides

2-sided

lower limit

0.893

upper limit

0.941

Stat 2

Statistical analysis description

Week 48. Serum B2M.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.914

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

0.939

Stat 3

Statistical analysis description

Week 24. Urine B2M.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.002

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.748

Confidence interval

level

95%

sides

2-sided

lower limit

0.621

upper limit

0.901

Stat 4

Statistical analysis description

Week 48. Urine B2M.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.005

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.693

Confidence interval

level

95%

sides

2-sided

lower limit

0.538

upper limit

0.892

Stat 5

Statistical analysis description

Week 24. Urine Albumin/Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.036

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.889

Confidence interval

level

95%

sides

2-sided

lower limit

0.796

upper limit

0.992

Stat 6

Statistical analysis description

Week 48. Urine Albumin/Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.308

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.938

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.061

Stat 7

Statistical analysis description

Week 24. Urine B2M/Urine Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.007

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.781

Confidence interval

level

95%

sides

2-sided

lower limit

0.654

upper limit

0.934

Stat 8

Statistical analysis description

Week 48. Urine B2M/Urine Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.012

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.742

Confidence interval

level

95%

sides

2-sided

lower limit

0.588

upper limit

0.935

Stat 9

Statistical analysis description

Week 24. Urine Phosphate.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.728

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.979

Confidence interval

level

95%

sides

2-sided

lower limit

0.868

upper limit

1.104

Stat 10

Statistical analysis description

Week 48. Urine Phosphate.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.311

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

1.062

Confidence interval

level

95%

sides

2-sided

lower limit

0.945

upper limit

1.194

Stat 11

Statistical analysis description

Week 24. Urine Protein/Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.826

Confidence interval

level

95%

sides

2-sided

lower limit

0.769

upper limit

0.887

Stat 12

Statistical analysis description

Week 48. Urine Protein/Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.795

upper limit

0.93

Stat 13

Statistical analysis description

Week 24. Urine RBP 4.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.003

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.796

Confidence interval

level

95%

sides

2-sided

lower limit

0.683

upper limit

0.927

Stat 14

Statistical analysis description

Week 48. Urine RBP 4.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.2

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.903

Confidence interval

level

95%

sides

2-sided

lower limit

0.773

upper limit

1.056

Stat 15

Statistical analysis description

Week 24. Urine RBP/Urine Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.003

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.826

Confidence interval

level

95%

sides

2-sided

lower limit

0.728

upper limit

0.936

Stat 16

Statistical analysis description

Week 48. Urine RBP/Urine Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.052

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.888

Confidence interval

level

95%

sides

2-sided

lower limit

0.787

upper limit

1.001

Secondary: Change from Baseline in bone biomarkers-Serum Bone Specific Alkaline Phosphatase (bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48

Top of page

End point title

Change from Baseline in bone biomarkers-Serum Bone Specific Alkaline Phosphatase (bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48

End point description

Blood samples were collected to perform evaluation of bone biomarkers which included bone-ALP, Serum Osteocalcin, PINP and CTX-1. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as value at the indicated time point minus Baseline value. Only those participants 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 at Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[40]	359 ^[41]
Units: Micrograms per Liter (ug/L)
arithmetic mean (standard error)
Bone-ALP, Week 24, n=345, 346	0.72 ( 0.171 )	3.38 ( 0.244 )
Bone-ALP, Week 48, n=334, 337	1.24 ( 0.198 )	4.33 ( 0.268 )
Serum Osteocalcin, Week 24, n=345, 346	2.13 ( 0.321 )	6.80 ( 0.368 )
Serum Osteocalcin, Week 48, n=335, 336	0.40 ( 0.326 )	6.30 ( 0.384 )
PINP, Week 24, n=344, 346	1.7 ( 0.95 )	15.2 ( 1.12 )
PINP, Week 48, n=335, 337	0.4 ( 0.79 )	13.3 ( 1.06 )
CTX-1, Week 24, n=342, 342	0.1541 ( 0.01247 )	0.2812 ( 0.01406 )
CTX-1, Week 48, n=332, 333	0.1345 ( 0.01496 )	0.3388 ( 0.01983 )

Notes
[40] - Safety Population
[41] - Safety Population

Stat 1

Statistical analysis description

Week 24, Bone ALP.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.66

Confidence interval

level

95%

sides

2-sided

lower limit

-3.25

upper limit

-2.08

Stat 2

Statistical analysis description

Week 48, Bone ALP.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.09

Confidence interval

level

95%

sides

2-sided

lower limit

-3.75

upper limit

-2.44

Stat 3

Statistical analysis description

Week 28, Serum Osteocalcin.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.67

Confidence interval

level

95%

sides

2-sided

lower limit

-5.63

upper limit

-3.71

Stat 4

Statistical analysis description

Week 48, Serum Osteocalcin.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.9

Confidence interval

level

95%

sides

2-sided

lower limit

-6.89

upper limit

-4.91

Stat 5

Statistical analysis description

Week 24, Serum PINP.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-16.4

upper limit

-10.6

Stat 6

Statistical analysis description

Week 48, Serum PINP.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-12.8

Confidence interval

level

95%

sides

2-sided

lower limit

-15.4

upper limit

-10.2

Stat 7

Statistical analysis description

Week 24, CTX-1

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.127

Confidence interval

level

95%

sides

2-sided

lower limit

-0.164

upper limit

-0.09

Stat 8

Statistical analysis description

Week 48, CTX-1.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.2043

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2532

upper limit

-0.1554

Secondary: Change from Baseline in bone biomarker-Serum Vitamin D at Weeks 24, 48

Top of page

End point title

Change from Baseline in bone biomarker-Serum Vitamin D at Weeks 24, 48

End point description

Blood samples were collected to perform evaluation of bone biomarker serum vitamin D. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as value at the indicated time point minus Baseline value.

End point type

Secondary

End point timeframe

Baseline and at Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[42]	359 ^[43]
Units: Nanomoles per Liter (nmol/L)
least squares mean (standard error)
Serum Vitamin D, Week 24, n=346, 344	11.2 ( 1.08 )	15.4 ( 1.33 )
Serum Vitamin D, Week 48, n=336, 335	0.3 ( 0.92 )	0.4 ( 1.01 )

Notes
[42] - Safety Population
[43] - Safety Population

Stat 1

Statistical analysis description

Week 24

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.015

Method

MMRM

Parameter type

Median difference (net)

Point estimate

-4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-7.5

upper limit

-0.8

Stat 2

Statistical analysis description

Week 48

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.96

Method

MMRM

Parameter type

Median difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

2.6

Secondary: Percentage change from Baseline in fasting lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48

Top of page

End point title

Percentage change from Baseline in fasting lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48

End point description

Blood samples were collected to perform evaluation of fasting lipids which included Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides. Baseline value is defined as the latest pre-dose assessment (Day 1). Percentage change from Baseline was calculated as 100 multiplied by ([post-dose visit value minus Baseline value] divided by Baseline value). Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and at Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[44]	359 ^[45]
Units: Percentage change
arithmetic mean (standard deviation)
Serum or Plasma Cholesterol, Week 24, n=298, 310	5.0 ( 16.85 )	-4.5 ( 15.44 )
Serum or Plasma Cholesterol, Week 48, n=298, 307	9.3 ( 17.10 )	-3.3 ( 14.61 )
HDL Cholesterol, Direct, Week 24, n=299, 310	13.9 ( 25.17 )	7.2 ( 32.22 )
HDL Cholesterol, Direct, Week 48, n=299, 307	15.3 ( 23.75 )	4.0 ( 21.86 )
LDL Cholesterol, Week 24, n=298, 309	3.8 ( 25.85 )	-7.8 ( 21.13 )
LDL Cholesterol, Week 48, n=297, 307	10.7 ( 27.54 )	-4.1 ( 20.39 )
Triglycerides ,Week 24, n=299, 310	7.0 ( 40.45 )	0.5 ( 44.01 )
Triglycerides , Week 48, n=299, 307	7.3 ( 46.92 )	-0.3 ( 49.22 )

Notes
[44] - Safety Population
[45] - Safety Population

No statistical analyses for this end point

Secondary: Percentage change from Baseline in fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48

Top of page

End point title

Percentage change from Baseline in fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48

End point description

Blood samples were collected to perform evaluation of fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio. Baseline value is the the latest pre-dose assessment (Day 1). Percentage change from Baseline was calculated as 100 multiplied by ([post-dose visit value minus Baseline value] divided by Baseline value) Lipid last observation carried forwardd (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent is used in place of future observed values. Participants on lipid-lowering agents at Baseline are excluded. Only those participants 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 at Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[46]	359 ^[47]
Units: Percentage change
arithmetic mean (standard deviation)
Total/HDL Cholesterol Ratio, Week 24, n=298, 310	-4.4 ( 22.53 )	-7.5 ( 17.90 )
Total/HDL Cholesterol Ratio, Week 48, n=298, 307	-2.8 ( 17.86 )	-4.5 ( 18.25 )

Notes
[46] - Safety Population
[47] - Safety Population

No statistical analyses for this end point

Secondary: Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Weeks 24, 48

Top of page

End point title

Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Weeks 24, 48

End point description

Blood samples were collected to perform evaluation of fasting LDL cholesterol. Any abnormalities were evaluated by the investigator and graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Weeks 24 and 48 have been presented. Participants without any post-Baseline fasting LDL cholesterol value prior to Week 48 or those who had Baseline lipids-lowering agents were not included. Lipid Last Observation Carried Forward (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

End point type

Secondary

End point timeframe

Weeks 24 and 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[48]	359 ^[49]
Units: Percentage of participants
Week 24, n=313, 320	4	0
Week 48, n=324, 332	4	2

Notes
[48] - Safety Population
[49] - Safety Population

Stat 1

Statistical analysis description

Week 24

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

Fisher exact

Parameter type

Mean difference (final values)

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

5.6

Stat 2

Statistical analysis description

Week 48

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

P-value

= 0.037 ^[50]

Method

Fisher exact

Parameter type

Mean difference (final values)

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

5.4

Notes
[50] - Fisher's exact p-value

Secondary: Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with plasma HIV-1 RNA <50 c/mL at Week 24

Top of page

End point title

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with plasma HIV-1 RNA <50 c/mL at Week 24

End point description

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of invetigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200 cells/mm3, >200 cells/mm3 for group-1), Baseline HIV-1 RNA (<=100000, >100000 c/mL) and Race (White, African American/African heritage, Asian other). Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Week 24

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[51]	359 ^[52]
Units: Percentage of participants
Baseline CD4+ cell count Group-1, <=200,n=32,26	78	92
Baseline CD4+ cell count Group-1, >200,n=328,333	95	94
Female, n=54, 46	93	89
Male, n=306, 313	94	95
Age, <35,n= 209, 203	93	94
Age, 35 to <50,n=115, 122	96	94
Age, >=50, n=36, 34	94	91
Baseline plasma HIV-1 RNA, <=100000,n=294,282	94	95
Baseline plasma HIV-1 RNA, >100000,n=66, 77	92	90
Race, White, n=237,249	95	95
Race, African American/African H., n=55, 40	89	90
Race, Asian, n=34, 30	97	90
Race, Other, n=34, 40	91	93

Notes
[51] - ITT-E Population
[52] - ITT-E Population

No statistical analyses for this end point

Secondary: Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count Baseline HIV-1 RNA, race) with plasma HIV-1 RNA <50 c/mL at Week 48

Top of page

End point title

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count Baseline HIV-1 RNA, race) with plasma HIV-1 RNA <50 c/mL at Week 48

End point description

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of invetigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200 cells/mm3, >200 cells/mm3 for group-1), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian and other). Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[53]	359 ^[54]
Units: Percentage of participants
Baseline CD4+ cell count Group-1, <=200,n=32, 26	78	96
Baseline CD4+ cell count Group-1, >200,n=328,333	95	94
Female, n=54, 46	89	87
Male, n=306, 313	94	95
Age, <35,n= 209,203	92	94
Age, 35 to <50,n=115, 122	97	94
Age, >=50, n=36, 34	89	94
Baseline plasma HIV-1 RNA, <=100000,n=294,282	92	95
Baseline plasma HIV-1 RNA, >100000,n=66, 77	97	90
Race, White, n=237,249	96	96
Race, African American/African H., n=55, 40	80	88
Race, Asian, n=34, 30	97	90
Race, Other, n=34, 40	88	90

Notes
[53] - ITT-E Population
[54] - ITT-E Population

No statistical analyses for this end point

Secondary: Changes from Baseline in CD4+ cell counts at Week 48 by subgroups

Top of page

End point title

Changes from Baseline in CD4+ cell counts at Week 48 by subgroups

End point description

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is the the latest pre-dose assessment. Change from Baseline was defined as value at the inidicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from Analysis of Covariance (ANCOVA) model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360	359
Units: Cells/mm^3
least squares mean (standard error)
Baseline plasma HIV-1 RNA,<=100000, n=273,271	215.6 ( 10.67 )	208.7 ( 10.71 )
Baseline plasma HIV-1 RNA,>100000, n=64,69	261.8 ( 22.27 )	248.7 ( 21.30 )
Baseline CD4+ cell count,<=200, n=28, 25	210.9 ( 33.42 )	153.2 ( 35.29 )
Baseline CD4+ cell count,>200, n=309, 315	225.8 ( 10.00 )	221.7 ( 9.89 )
Age group-1, <35,n= 193, 191	234.2 ( 12.67 )	201.7 ( 12.72 )
Age group-1, 35 to <50, n=112, 117	212.7 ( 16.59 )	244.2 ( 16.31 )
Age group-1, >=50, n=32, 32	209.1 ( 31.20 )	203.9 ( 31.06 )
Age group-2, <50,n= 305, 308	226.4 ( 10.09 )	217.8 ( 10.03 )
Age group-2, >=50, n= 32, 32	208.5 ( 31.27 )	204.1 ( 31.14 )
Female, n=48, 41	236.2 ( 25.35 )	263.6 ( 27.50 )
Male, n=289, 299	222.8 ( 10.33 )	210.0 ( 10.17 )
Race group, White, n=227, 241	223.3 ( 11.70 )	214.2 ( 11.38 )
Race group, African Am/African H., n=45, 36	214.0 ( 26.25 )	233.7 ( 29.39 )
Race group, Asian, n=33, 27	205.0 ( 30.92 )	189.3 ( 33.90 )
Race group, Other, n=32, 36	270.2 ( 31.16 )	235.3 ( 29.47 )

Stat 1

Statistical analysis description

Baseline plasma HIV-1 RNA,<=100000. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, Baseline plasma HIV-1 RNA, and treatment and relevant Baseline plasma HIV-1 RNA interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

6.9

Confidence interval

level

95%

sides

2-sided

lower limit

-22.7

upper limit

36.6

Stat 2

Statistical analysis description

Baseline plasma HIV-1 RNA,>100000. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, Baseline plasma HIV-1 RNA, and treatment and Baseline plasma HIV-1 RNA interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

13.2

Confidence interval

level

95%

sides

2-sided

lower limit

-46.8

upper limit

73.2

Stat 3

Statistical analysis description

Baseline CD4+ cell count,<=200. Following covariates were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and Baseline CD4+ cell count interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

57.7

Confidence interval

level

95%

sides

2-sided

lower limit

-37.2

upper limit

152.5

Stat 4

Statistical analysis description

Baseline CD4+ cell count,>200. Following covariates were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and Baseline CD4+ cell count interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-23.5

upper limit

31.7

Stat 5

Statistical analysis description

Age Group-1,<35. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

32.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

67.7

Stat 6

Statistical analysis description

Age Group-1,35 to <50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-31.5

Confidence interval

level

95%

sides

2-sided

lower limit

-77.1

upper limit

14.2

Stat 7

Statistical analysis description

Age Group-1,>=50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-81.4

upper limit

91.8

Stat 10

Statistical analysis description

Female. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-27.3

Confidence interval

level

95%

sides

2-sided

lower limit

-100.8

upper limit

46.1

Stat 11

Statistical analysis description

Male. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

12.8

Confidence interval

level

95%

sides

2-sided

lower limit

-15.7

upper limit

41.2

Stat 12

Statistical analysis description

Race group-white. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

9.1

Confidence interval

level

95%

sides

2-sided

lower limit

-22.9

upper limit

41.1

Stat 13

Statistical analysis description

Race group-African Am/African H. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-19.8

Confidence interval

level

95%

sides

2-sided

lower limit

-97.1

upper limit

57.6

Stat 14

Statistical analysis description

Race group-Asian. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

15.7

Confidence interval

level

95%

sides

2-sided

lower limit

-74.4

upper limit

105.9

Stat 15

Statistical analysis description

Race group-Other. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-49

upper limit

119

Secondary: Changes from Baseline in CD4+ cell counts at Week 24 by subgroups

Top of page

End point title

Changes from Baseline in CD4+ cell counts at Week 24 by subgroups

End point description

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. It was evaluated by flow cytometry. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only. Only those participants 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 24

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[55]	359 ^[56]
Units: Cells/mm^3
arithmetic mean (standard error)
Baseline plasma HIV-1 RNA,<=100000, n=283,273	186.01 ( 9.948 )	148.21 ( 10.134 )
Baseline plasma HIV-1 RNA,>100000, n=66,72	193.90 ( 20.811 )	220.71 ( 19.814 )
Baseline CD4+ cell count,<=200, n=29, 26	167.95 ( 31.308 )	106.23 ( 32.990 )
Baseline CD4+ cell count,>200, n=320, 319	189.91 ( 9.362 )	167.35 ( 9.362 )
Age group, <35,n= 201, 193	190.12 ( 11.829 )	151.13 ( 12.050 )
Age group-1, 35 to <50, n=113, 119	180.50 ( 15.733 )	190.40 ( 15.404 )
Age group-1, >=50, n=32, 32	198.74 ( 28.411 )	133.21 ( 29.120 )
Female, n=52, 42	213.58 ( 23.225 )	153.92 ( 25.910 )
Male, n=297, 303	183.41 ( 9.719 )	164.18 ( 9.631 )
Race group, White, n=233, 240	182.20 ( 10.987 )	168.30 ( 10.846 )
Race group, African Am/African H., n=51, 39	214.17 ( 23.472 )	145.44 ( 26.841 )
Race group, Asian, n=33, 28	154.14 ( 29.401 )	141.22 ( 31.663 )
Race group, Other, n=32, 38	222.24 ( 29.643 )	163.05 ( 27.293 )

Notes
[55] - ITT-E Population.
[56] - ITT-E Population.

Stat 1

Statistical analysis description

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (net)

Point estimate

37.8

Confidence interval

level

95%

sides

2-sided

lower limit

9.98

upper limit

65.62

Stat 2

Statistical analysis description

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-26.81

Confidence interval

level

95%

sides

2-sided

lower limit

-82.72

upper limit

29.1

Stat 3

Statistical analysis description

Baseline CD4+ cell count,<=200. Following covariates were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and Baseline CD4+ cell count interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

61.72

Confidence interval

level

95%

sides

2-sided

lower limit

-26.94

upper limit

150.39

Stat 4

Statistical analysis description

Baseline CD4+ cell count,>200. Following covariates were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and Baseline CD4+ cell count interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (net)

Point estimate

22.57

Confidence interval

level

95%

sides

2-sided

lower limit

-3.42

upper limit

48.55

Stat 5

Statistical analysis description

Age Group,<35. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

38.99

Confidence interval

level

95%

sides

2-sided

lower limit

5.88

upper limit

72.09

Stat 6

Statistical analysis description

Age Group,35 to <50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-9.9

Confidence interval

level

95%

sides

2-sided

lower limit

-53.1

upper limit

33.3

Stat 7

Statistical analysis description

Age Group,>=50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

65.53

Confidence interval

level

95%

sides

2-sided

lower limit

-14.43

upper limit

145.5

Stat 8

Statistical analysis description

Female. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

59.66

Confidence interval

level

95%

sides

2-sided

lower limit

-8.62

upper limit

127.94

Stat 9

Statistical analysis description

Male. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

19.23

Confidence interval

level

95%

sides

2-sided

lower limit

-7.65

upper limit

46.1

Stat 10

Statistical analysis description

Race group-white. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

13.9

Confidence interval

level

95%

sides

2-sided

lower limit

-16.35

upper limit

44.15

Stat 11

Statistical analysis description

Race group-African Am/African H. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

68.74

Confidence interval

level

95%

sides

2-sided

lower limit

-1.24

upper limit

138.72

Stat 12

Statistical analysis description

Race group-Asian. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

12.93

Confidence interval

level

95%

sides

2-sided

lower limit

-71.9

upper limit

97.75

Stat 13

Statistical analysis description

Race group-Other. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

59.19

Confidence interval

level

95%

sides

2-sided

lower limit

-19.73

upper limit

138.11

Secondary: Change from Baseline in European Quality of Life (EuroQoL) – 5 Dimensions – 5 Levels (EQ-5D-5L) utility score at Weeks 4, 24 48

Top of page

End point title

Change from Baseline in European Quality of Life (EuroQoL) – 5 Dimensions – 5 Levels (EQ-5D-5L) utility score at Weeks 4, 24 48

End point description

EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The 5-item measure has 1 question assessing each of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no, 2=slight , 3=moderate, 4=severe and 5=extreme problems. The health state is defined by combining the levels of answers from each of the 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health. MMRM was run on LOCF dataset. Baseline was the latest pre-dose assessment and change from Baseline=post-dose value minus Baseline value. Only those participants 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 Weeks 4, 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[57]	359 ^[58]
Units: Scores on a scale
least squares mean (standard error)
Week 4, n=359, 355	0.0111 ( 0.00326 )	0.0130 ( 0.00510 )
Week 24, n=360, 358	0.0207 ( 0.00310 )	0.0203 ( 0.00347 )
Week 48, n=360, 358	0.0189 ( 0.00362 )	0.0208 ( 0.00342 )

Notes
[57] - ITT-E Population.
[58] - ITT-E Population.

Stat 1

Statistical analysis description

Week 4. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA , Baseline CD4+ cell count , and Baseline EQ-5D utility, treatment*visit and Baseline EQ- 5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.759

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.0019

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0137

upper limit

0.01

Stat 2

Statistical analysis description

Week 24. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA , Baseline CD4+ cell count, and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.943

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.0003

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0088

upper limit

0.0095

Stat 3

Statistical analysis description

Week 48. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA , Baseline CD4+ cell count, and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.703

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.0019

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0117

upper limit

0.0079

Secondary: Change from Baseline in EuroQol – 5 Dimensions – 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24 48

Top of page

End point title

Change from Baseline in EuroQol – 5 Dimensions – 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24 48

End point description

EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The 5-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value and change from Baseline=post-dose value minus Baseline value. Only those participants 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 Weeks 4, 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[59]	359 ^[60]
Units: Scores on a scale
least squares mean (standard error)
Week 4, n=358, 355	1.8 ( 0.50 )	3.1 ( 0.41 )
Week 24, n=359, 358	3.9 ( 0.43 )	4.5 ( 0.48 )
Week 48, n=359, 358	4.0 ( 0.43 )	4.6 ( 0.48 )

Notes
[59] - ITT-E Population.
[60] - ITT-E Population.

Stat 1

Statistical analysis description

Week 4. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count and Baseline EQ-5D utility, treatment*visit and Baseline EQ- 5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.045

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

Stat 2

Statistical analysis description

Week 24. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.358

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.7

Stat 3

Statistical analysis description

Week 48. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.328

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.6

Adverse events

Top of page

Timeframe for reporting adverse events

Post-Baseline SAEs and non-SAEs were collected from start of the study treatment up to Week 48 (data cut-off for primary analysis).

Adverse event reporting additional description

Post-Baseline SAEs and non-serious AEs were reported for the Safety Population.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

DTG + 3TC

Reporting group description

Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.

Reporting group title

DTG + TDF/FTC

Reporting group description

Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.

Serious adverse events	DTG + 3TC	DTG + TDF/FTC
Total subjects affected by serious adverse events
subjects affected / exposed	29 / 360 (8.06%)	33 / 359 (9.19%)
number of deaths (all causes)	2	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
subjects affected / exposed	2 / 360 (0.56%)	3 / 359 (0.84%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Anal cancer stage 0
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
B-cell lymphoma
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Burkitt's lymphoma
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Non-Hodgkin's lymphoma
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fracture
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Fracture of penis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intentional overdose
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple fractures
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Penetrating abdominal trauma
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural complication
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Thermal burn
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Tachycardia
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Sciatica
subjects affected / exposed	1 / 360 (0.28%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Ophthalmic vein thrombosis
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 360 (0.28%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal hernia
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	0 / 360 (0.00%)	2 / 359 (0.56%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatotoxicity
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Suicide attempt
subjects affected / exposed	3 / 360 (0.83%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 3	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	1 / 360 (0.28%)	2 / 359 (0.56%)
occurrences causally related to treatment / all	1 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Acute psychosis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Alcoholic psychosis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Urethral meatus stenosis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Hepatitis A
subjects affected / exposed	3 / 360 (0.83%)	3 / 359 (0.84%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Acute hepatitis C
subjects affected / exposed	1 / 360 (0.28%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 360 (0.28%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial colitis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Epididymitis
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Salmonellosis
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Soft tissue infection
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tuberculous pleurisy
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Varicella zoster virus infection
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	DTG + 3TC	DTG + TDF/FTC
Total subjects affected by non serious adverse events
subjects affected / exposed	189 / 360 (52.50%)	215 / 359 (59.89%)
Nervous system disorders
Headache
subjects affected / exposed	31 / 360 (8.61%)	31 / 359 (8.64%)
occurrences all number	38	36
Dizziness
subjects affected / exposed	7 / 360 (1.94%)	13 / 359 (3.62%)
occurrences all number	9	14
General disorders and administration site conditions
Fatigue
subjects affected / exposed	10 / 360 (2.78%)	6 / 359 (1.67%)
occurrences all number	12	6
Influenza like illness
subjects affected / exposed	10 / 360 (2.78%)	6 / 359 (1.67%)
occurrences all number	11	6
Pyrexia
subjects affected / exposed	8 / 360 (2.22%)	5 / 359 (1.39%)
occurrences all number	8	6
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	35 / 360 (9.72%)	35 / 359 (9.75%)
occurrences all number	40	38
Nausea
subjects affected / exposed	15 / 360 (4.17%)	23 / 359 (6.41%)
occurrences all number	15	24
Abdominal pain
subjects affected / exposed	6 / 360 (1.67%)	12 / 359 (3.34%)
occurrences all number	6	13
Haemorrhoids
subjects affected / exposed	8 / 360 (2.22%)	10 / 359 (2.79%)
occurrences all number	8	10
Constipation
subjects affected / exposed	8 / 360 (2.22%)	8 / 359 (2.23%)
occurrences all number	9	8
Toothache
subjects affected / exposed	7 / 360 (1.94%)	9 / 359 (2.51%)
occurrences all number	7	9
Vomiting
subjects affected / exposed	8 / 360 (2.22%)	8 / 359 (2.23%)
occurrences all number	8	8
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	11 / 360 (3.06%)	9 / 359 (2.51%)
occurrences all number	13	9
Cough
subjects affected / exposed	7 / 360 (1.94%)	8 / 359 (2.23%)
occurrences all number	7	8
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	4 / 360 (1.11%)	10 / 359 (2.79%)
occurrences all number	4	11
Psychiatric disorders
Insomnia
subjects affected / exposed	11 / 360 (3.06%)	16 / 359 (4.46%)
occurrences all number	11	19
Anxiety
subjects affected / exposed	9 / 360 (2.50%)	11 / 359 (3.06%)
occurrences all number	9	11
Depression
subjects affected / exposed	6 / 360 (1.67%)	8 / 359 (2.23%)
occurrences all number	6	8
Renal and urinary disorders
Dysuria
subjects affected / exposed	8 / 360 (2.22%)	2 / 359 (0.56%)
occurrences all number	8	2
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	16 / 360 (4.44%)	12 / 359 (3.34%)
occurrences all number	18	14
Arthralgia
subjects affected / exposed	10 / 360 (2.78%)	15 / 359 (4.18%)
occurrences all number	11	15
Infections and infestations
Nasopharyngitis
subjects affected / exposed	22 / 360 (6.11%)	41 / 359 (11.42%)
occurrences all number	28	47
Upper respiratory tract infection
subjects affected / exposed	32 / 360 (8.89%)	22 / 359 (6.13%)
occurrences all number	38	26
Pharyngitis
subjects affected / exposed	13 / 360 (3.61%)	19 / 359 (5.29%)
occurrences all number	15	19
Influenza
subjects affected / exposed	8 / 360 (2.22%)	17 / 359 (4.74%)
occurrences all number	8	19
Syphilis
subjects affected / exposed	10 / 360 (2.78%)	12 / 359 (3.34%)
occurrences all number	12	12
Respiratory tract infection viral
subjects affected / exposed	11 / 360 (3.06%)	9 / 359 (2.51%)
occurrences all number	13	13
Bronchitis
subjects affected / exposed	8 / 360 (2.22%)	10 / 359 (2.79%)
occurrences all number	9	11
Gastroenteritis
subjects affected / exposed	7 / 360 (1.94%)	11 / 359 (3.06%)
occurrences all number	7	13
Tonsillitis
subjects affected / exposed	10 / 360 (2.78%)	8 / 359 (2.23%)
occurrences all number	10	9
Gonorrhoea
subjects affected / exposed	9 / 360 (2.50%)	7 / 359 (1.95%)
occurrences all number	9	8
Chlamydial infection
subjects affected / exposed	7 / 360 (1.94%)	8 / 359 (2.23%)
occurrences all number	8	8
Rhinitis
subjects affected / exposed	2 / 360 (0.56%)	9 / 359 (2.51%)
occurrences all number	2	9
Genital herpes
subjects affected / exposed	1 / 360 (0.28%)	8 / 359 (2.23%)
occurrences all number	1	12
Metabolism and nutrition disorders
Vitamin D deficiency
subjects affected / exposed	8 / 360 (2.22%)	4 / 359 (1.11%)
occurrences all number	8	4

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Were there any global substantial amendments to the protocol? Yes

29 Nov 2017

The double barrier method of contraception (male condom combined with a vaginal spermicide) was added as a permitted method for preventing pregnancy in females of reproductive potential. Exclusion criterion 15 (limitations on investigational drug use) was broadened to include additional countries as needed. Inclusion of Portugal was required by the Portuguese National Ethics Committee for Clinical Research. Assessment of weight at Weeks 96 and 144 was added to monitor the incidence of significant weight gain with DTG use. Assessment of inflammation biomarkers ([interleukin {IL}-6, high sensitivity C-reactive protein {hs-CRP}) at Day 1, and Weeks 48, 96 and 144, and Assessment of telomere length at Day 1, and Weeks 96 and 144, were added as new exploratory endpoints. For clarification purposes, the peripheral blood mononuclear cell (PBMC) sample in Section 7.1 (Time and Events table) and Section 7.6.1 (Human immuno deficiency virus [HIV-1] Exploratory Analyses) was renamed as a whole blood sample. The Day 1 PBMC sample (now named whole blood sample) originally designated for virology use was additionally designated for telomere length measurement, where possible. Additional whole blood samples were added for measurement of telomere length at Week 96 and Week 144. A description of commercial image DTG tablets was added to Section 6.1 (Investigational Product and Other Study Treatment) to allow use of commercial material as well as clinical trial material. The physical description for open-label lamivudine in Section 6.1 was corrected. Standard procedures for forwarding pregnancy information to the Antiretroviral Pregnancy Register were added. For clarification purposes, the AE severity grading’s in Appendix 7, Section 12.7.6 (Evaluating AEs and SAEs) were updated to be consistent with Appendix 6, Section 12.6. (Division of AIDS table for Grading Severity of Adult and Pediatric AEs). This change has no impact on the investigators evaluation of AEs.

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

Clinical Trial Results: A Phase III, randomised, double-blind, multicentre, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of dolutegravir plus lamivudine compared to dolutegravir plus tenofovir/emtricitabine in HIV-1-infected treatment-naïve adults

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants with plasma Human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL (c/mL) at Week 48

Primary: Percentage of participants with plasma Human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL (c/mL) at Week 48

Secondary: Percentage of participants with plasma HIV-1 RNA <50 c/mL at Weeks 24

Secondary: Percentage of participants with plasma HIV-1 RNA <50 c/mL at Weeks 24

Secondary: Time to viral suppression (HIV-1 RNA <50 c/mL)

Secondary: Time to viral suppression (HIV-1 RNA <50 c/mL)

Secondary: CD4+ cell counts at Weeks 24 and 48

Secondary: CD4+ cell counts at Weeks 24 and 48

Secondary: Changes from Baseline in CD4+ cell counts at Week 24 and 48

Secondary: Changes from Baseline in CD4+ cell counts at Week 24 and 48

Secondary: Number of participants with HIV-1 Disease Progression

Secondary: Number of participants with HIV-1 Disease Progression

Secondary: Number of participants with treatment-emergent genotypic resistance

Secondary: Number of participants with treatment-emergent genotypic resistance

Secondary: Number of participants with treatment-emergent phenotypic resistance

Secondary: Number of participants with treatment-emergent phenotypic resistance

Secondary: Number of participants with any adverse event (AE) and serious AE (SAE)

Secondary: Number of participants with any adverse event (AE) and serious AE (SAE)

Secondary: Number of participants with AEs by maximum severity grades

Secondary: Number of participants with AEs by maximum severity grades

Secondary: Number of participants with any drug related AEs and drug related AEs by maximum grade

Secondary: Number of participants with any drug related AEs and drug related AEs by maximum grade

Secondary: Number of participants with maximum post-Baseline emergent hematology toxicities

Secondary: Number of participants with maximum post-Baseline emergent hematology toxicities

Secondary: Number of participants with maximum post-Baseline emergent chemistry toxicities

Secondary: Number of participants with maximum post-Baseline emergent chemistry toxicities

Secondary: Number of participants who discontinue treatment due to AEs over Weeks 24, 48

Secondary: Number of participants who discontinue treatment due to AEs over Weeks 24, 48

Secondary: Change from Baseline in renal biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48

Secondary: Change from Baseline in renal biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48

Secondary: Change from Baseline in renal biomarkers-Serum GFR from cystatin C Adjusted using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR from creatinine adjusted using CKD-EPI at Weeks 24, 48

Secondary: Change from Baseline in renal biomarkers-Serum GFR from cystatin C Adjusted using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR from creatinine adjusted using CKD-EPI at Weeks 24, 48

Secondary: Change from Baseline in renal biomarker-Serum or Plasma Creatinine at Weeks 24, 48

Secondary: Change from Baseline in renal biomarker-Serum or Plasma Creatinine at Weeks 24, 48

Secondary: Ratio to Baseline in renal biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48

Secondary: Ratio to Baseline in renal biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48

Secondary: Change from Baseline in bone biomarkers-Serum Bone Specific Alkaline Phosphatase (bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48

Secondary: Change from Baseline in bone biomarkers-Serum Bone Specific Alkaline Phosphatase (bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48

Secondary: Change from Baseline in bone biomarker-Serum Vitamin D at Weeks 24, 48

Secondary: Change from Baseline in bone biomarker-Serum Vitamin D at Weeks 24, 48

Secondary: Percentage change from Baseline in fasting lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48

Secondary: Percentage change from Baseline in fasting lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48

Secondary: Percentage change from Baseline in fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48

Secondary: Percentage change from Baseline in fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48

Secondary: Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Weeks 24, 48

Secondary: Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Weeks 24, 48

Secondary: Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with plasma HIV-1 RNA <50 c/mL at Week 24

Secondary: Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with plasma HIV-1 RNA <50 c/mL at Week 24

Secondary: Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count Baseline HIV-1 RNA, race) with plasma HIV-1 RNA <50 c/mL at Week 48

Secondary: Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count Baseline HIV-1 RNA, race) with plasma HIV-1 RNA <50 c/mL at Week 48

Secondary: Changes from Baseline in CD4+ cell counts at Week 48 by subgroups

Secondary: Changes from Baseline in CD4+ cell counts at Week 48 by subgroups

Secondary: Changes from Baseline in CD4+ cell counts at Week 24 by subgroups

Secondary: Changes from Baseline in CD4+ cell counts at Week 24 by subgroups

Secondary: Change from Baseline in European Quality of Life (EuroQoL) – 5 Dimensions – 5 Levels (EQ-5D-5L) utility score at Weeks 4, 24 48

Secondary: Change from Baseline in European Quality of Life (EuroQoL) – 5 Dimensions – 5 Levels (EQ-5D-5L) utility score at Weeks 4, 24 48

Secondary: Change from Baseline in EuroQol – 5 Dimensions – 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24 48

Secondary: Change from Baseline in EuroQol – 5 Dimensions – 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24 48

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase III, randomised, double-blind, multicentre, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of dolutegravir plus lamivudine compared to dolutegravir plus tenofovir/emtricitabine in HIV-1-infected treatment-naïve adults