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An Efficacy, Safety, and Tolerability Study Comparing Dolutegravir Plus Lamivudine With Dolutegravir Plus Tenofovir/Emtricitabine in Treatment naïve HIV Infected Subjects (Gemini 1)

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ClinicalTrials.gov Identifier: NCT02831673
Recruitment Status : Active, not recruiting
First Posted : July 13, 2016
Results First Posted : April 18, 2019
Last Update Posted : August 9, 2019
Sponsor:
Collaborators:
PPD
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Infection, Human Immunodeficiency Virus
HIV Infections
Interventions Drug: Dolutegravir (DTG)
Drug: Lamivudine (3TC)
Drug: Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC FDC)
Enrollment 719
Recruitment Details This study is a randomized, double-blind, parallel-group, non-inferiority study. A total of 87 investigational centers in 18 countries randomized one or more participants. The results are presented based on primary analysis at Week 48. Analysis presented used a data cut-off date of 22-May-2018 (for Week 48 database freeze).
Pre-assignment Details Total of 719 participants were enrolled and randomized, however only 714 were dosed in the study and 5 were not dosed due to physician decision (3), protocol deviation (1) and participant's own decision (1).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks. Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Period Title: Overall Study
Started 356 358
Completed 0 0
Not Completed 356 358
Reason Not Completed
Adverse Event             6             4
Lack of Efficacy             3             1
Protocol Violation             5             4
Protocol Withdrawal Criterion Met             1             6
Lost to Follow-up             9             6
Physician Decision             6             3
Withdrawal by Subject             6             4
Ongoing at Week 48 primary analysis.             320             330
Arm/Group Title DTG + 3TC DTG + TDF/FTC Total
Hide Arm/Group Description Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks. Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks. Total of all reporting groups
Overall Number of Baseline Participants 356 358 714
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 356 participants 358 participants 714 participants
34.0  (9.88) 35.0  (10.72) 34.5  (10.31)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 356 participants 358 participants 714 participants
Female
59
  16.6%
52
  14.5%
111
  15.5%
Male
297
  83.4%
306
  85.5%
603
  84.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 356 participants 358 participants 714 participants
American (Am) Indian or Alaska (Al.) native
28
   7.9%
28
   7.8%
56
   7.8%
Asian-Central/South Asian heritage (H.)
0
   0.0%
4
   1.1%
4
   0.6%
Asian - East Asian H.
33
   9.3%
36
  10.1%
69
   9.7%
Asian - South East Asian H.
4
   1.1%
2
   0.6%
6
   0.8%
Black or African Am
44
  12.4%
36
  10.1%
80
  11.2%
Native Hawaiian or other Pacific Islander
2
   0.6%
0
   0.0%
2
   0.3%
White (Wt)-Arabic/North African H.
5
   1.4%
6
   1.7%
11
   1.5%
Wt-Wt/Caucasian (Ca.)/European (Eu.) H.
238
  66.9%
242
  67.6%
480
  67.2%
Black or African Am and Am Indian or Al. native
0
   0.0%
1
   0.3%
1
   0.1%
Black or African Am and Wt-Wt/Ca./Eu. H.
1
   0.3%
1
   0.3%
2
   0.3%
Am Indian or Al. native and Wt-Wt/Ca./Eu. H.
1
   0.3%
2
   0.6%
3
   0.4%
1.Primary Outcome
Title Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL (c/mL) at Week 48
Hide 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 investigational 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.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
90
(86.8 to 93.0)
93
(90.0 to 95.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments 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 greater than -10%.
Method of Estimation Estimation Parameter Adjusted difference in proportion
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-6.7 to 1.5
Estimation Comments Difference in proportion was based on CMH stratified analysis adjusting for Baseline stratification factors: Plasma HIV-1 RNA (<=versus [vs.]>100,000 c/mL) and cluster of differentiation 4+ (CD4+) cell count (<= vs. >200 cells per cubic millimeter).
2.Secondary Outcome
Title Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24
Hide 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 Cochran-Mantel-Haenszel weights.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
92
(89.7 to 95.2)
93
(90.4 to 95.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted difference in proportion
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-4.2 to 3.4
Estimation Comments Difference in proportion was based on CMH stratified analysis adjusting for Baseline stratification factors: Plasma HIV-1 RNA (<=vs.>100,000 c/mL) and CD4+ cell count (<= vs. >200 cells per cubic millimeter).
3.Secondary Outcome
Title Time to Viral Suppression (HIV-1 RNA <50 c/mL)
Hide 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 interquartile range (first Quartile and third Quartile) have been presented.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Median (Inter-Quartile Range)
Unit of Measure: Days
29.0
(29.0 to 52.0)
29.0
(29.0 to 56.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.558
Comments The generalized Wilcoxon procedure was used to estimate a p-value for detecting a difference in cumulative incidence curves between treatment groups.
Method Generalized Wilcoxon procedure
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.87 to 1.17
Estimation Comments Hazard ratios were estimated using the Cox proportional hazard regression model. A hazard ratio of >1 indicates that DTG + 3TC is more likely to reach viral suppression earlier than DTG + TDF/FTC.
4.Secondary Outcome
Title CD4+ Cell Counts at Weeks 24 and 48
Hide 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.
Time Frame Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Mean (Standard Deviation)
Unit of Measure: Cells per cubic millimeter (cells/mm^3)
Week 24, n=340,341 Number Analyzed 340 participants 341 participants
655.3  (288.32) 632.8  (262.61)
Week 48, n=324,334 Number Analyzed 324 participants 334 participants
687.7  (275.47) 675.3  (274.46)
5.Secondary Outcome
Title Changes From Baseline in CD4+ Cell Counts at Week 24 and 48
Hide 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 defined as the the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted 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.
Time Frame Baseline (Day 1) and Weeks 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Mean (Standard Error)
Unit of Measure: Cells per cubic millimeter
Week 24, n=340,341 Number Analyzed 340 participants 341 participants
192.2  (9.67) 175.1  (9.41)
Week 48, n=324,334 Number Analyzed 324 participants 334 participants
222.2  (9.87) 217.7  (10.64)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.206
Comments [Not Specified]
Method Mixed Model Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 17.1
Confidence Interval (2-Sided) 95%
-9.4 to 43.6
Estimation Comments 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.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.754
Comments [Not Specified]
Method Mixed Model Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.6
Confidence Interval (2-Sided) 95%
-23.9 to 33.0
Estimation Comments 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.
6.Secondary Outcome
Title Number of Participants With HIV-1 Disease Progression
Hide 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 progression 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 enrolment 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 enrolment to Death.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Measure Type: Count of Participants
Unit of Measure: Participants
No HIV-1 disease progression
352
  98.9%
356
  99.4%
From CDC Stage 1 to CDC Stage 3 Event
0
   0.0%
0
   0.0%
From CDC Stage 2 to CDC Stage 3 Event
2
   0.6%
2
   0.6%
From CDC Stage 3 to New CDC Stage 3 Event
2
   0.6%
0
   0.0%
From CDC Stage 1, 2 or 3 to Death
0
   0.0%
0
   0.0%
7.Secondary Outcome
Title Number of Participants With Treatment-emergent Genotypic Resistance
Hide Description Number of participants, who meet confirmed virologic withdrawal (CVW) criteria, with treatment emergent phenotypic 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.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Viral Genotypic Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 4 2
Measure Type: Count of Participants
Unit of Measure: Participants
INSTI Mutations
0
   0.0%
0
   0.0%
Major mutations of NRTI
0
   0.0%
0
   0.0%
8.Secondary Outcome
Title Number of Participants With Treatment-emergent Phenotypic Resistance
Hide 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 was interpreted through a proprietary algorithm (from Monogram Biosciences) and provides the overall susceptibility of the drug. Partially sensitive and resistant calls 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.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Viral Phenotypic Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 4 2
Measure Type: Count of Participants
Unit of Measure: Participants
INSTI, DTG, Sensitive, n=4,1 Number Analyzed 4 participants 1 participants
4
 100.0%
1
 100.0%
INSTI, DTG, Resistant, n=4,1 Number Analyzed 4 participants 1 participants
0
   0.0%
0
   0.0%
INSTI, EVG, Sensitive, n=4,1 Number Analyzed 4 participants 1 participants
4
 100.0%
1
 100.0%
INSTI, EVG, Resistant, n=4,1 Number Analyzed 4 participants 1 participants
0
   0.0%
0
   0.0%
INSTI, RAL, Sensitive, n=4,1 Number Analyzed 4 participants 1 participants
4
 100.0%
1
 100.0%
INSTI, RAL, Resistant, n=4,1 Number Analyzed 4 participants 1 participants
0
   0.0%
0
   0.0%
NRTI, 3TC, Sensitive, n=4,2 Number Analyzed 4 participants 2 participants
4
 100.0%
2
 100.0%
NRTI, 3TC, Resistant, n=4,2 Number Analyzed 4 participants 2 participants
0
   0.0%
0
   0.0%
NRTI, ABC, Sensitive, n=4,2 Number Analyzed 4 participants 2 participants
4
 100.0%
2
 100.0%
NRTI, ABC, Resistant, n=4,2 Number Analyzed 4 participants 2 participants
0
   0.0%
0
   0.0%
NRTI, AZT, Sensitive, n=4,2 Number Analyzed 4 participants 2 participants
4
 100.0%
2
 100.0%
NRTI, AZT, Resistant, n=4,2 Number Analyzed 4 participants 2 participants
0
   0.0%
0
   0.0%
NRTI, D4T, Sensitive, n=4,2 Number Analyzed 4 participants 2 participants
4
 100.0%
2
 100.0%
NRTI, D4T, Resistant, n=4,2 Number Analyzed 4 participants 2 participants
0
   0.0%
0
   0.0%
NRTI, DDI, Sensitive, n=4,2 Number Analyzed 4 participants 2 participants
4
 100.0%
2
 100.0%
NRTI, DDI, Resistant, n=4,2 Number Analyzed 4 participants 2 participants
0
   0.0%
0
   0.0%
NRTI, FTC, Sensitive, n=4,2 Number Analyzed 4 participants 2 participants
4
 100.0%
2
 100.0%
NRTI, FTC, Resistant, n=4,2 Number Analyzed 4 participants 2 participants
0
   0.0%
0
   0.0%
NRTI, TDF, Sensitive, n=4,2 Number Analyzed 4 participants 2 participants
4
 100.0%
2
 100.0%
NRTI, TDF, Resistant, n=4,2 Number Analyzed 4 participants 2 participants
0
   0.0%
0
   0.0%
9.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) and Serious AE (SAE)
Hide 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.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
276
  77.5%
295
  82.4%
Any SAE
21
   5.9%
22
   6.1%
10.Secondary Outcome
Title Number of Participants With AEs by Their Severity Grades
Hide 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.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1 AEs
60
  16.9%
61
  17.0%
Grade 2 AEs
195
  54.8%
210
  58.7%
Grade 3 AEs
19
   5.3%
22
   6.1%
Grade 4 AEs
2
   0.6%
2
   0.6%
Grade 5 AEs
0
   0.0%
0
   0.0%
11.Secondary Outcome
Title Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade
Hide 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 maximum grade have been presented.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Measure Type: Count of Participants
Unit of Measure: Participants
Any drug related AE
71
  19.9%
94
  26.3%
Drug related AEs with maximum toxicity Grade 1
50
  14.0%
69
  19.3%
Drug related AEs with maximum toxicity Grade 2
18
   5.1%
22
   6.1%
Drug related AEs with maximum toxicity Grade 3
3
   0.8%
3
   0.8%
Drug related AEs with maximum toxicity Grade 4
0
   0.0%
0
   0.0%
Drug related AEs with maximum toxicity Grade 5
0
   0.0%
0
   0.0%
12.Secondary Outcome
Title Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities
Hide Description Blood samples were collected up to Week 48 for assessment of hematology parameters to assess any abnormality per toxicity scales for platelet count, neutrophils, hemoglobin. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent hematology toxicities in any of the hematology parameters have been presented.
Time Frame Up to Week 48
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Hide Analysis Population Description
Safety Population
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin, Grades 1 to 4
7
   2.0%
5
   1.4%
Hemoglobin, Grades 2 to 4
1
   0.3%
1
   0.3%
Hemoglobin, Grades 3 to 4
0
   0.0%
0
   0.0%
Hemoglobin, Grade 1
6
   1.7%
4
   1.1%
Hemoglobin, Grade 2
1
   0.3%
1
   0.3%
Hemoglobin, Grade 3
0
   0.0%
0
   0.0%
Hemoglobin, Grade 4
0
   0.0%
0
   0.0%
Leukocytes, Grades 1 to 4
5
   1.4%
3
   0.8%
Leukocytes, Grades 2 to 4
2
   0.6%
2
   0.6%
Leukocytes, Grades 3 to 4
0
   0.0%
0
   0.0%
Leukocytes, Grade 1
3
   0.8%
1
   0.3%
Leukocytes, Grade 2
2
   0.6%
2
   0.6%
Leukocytes, Grade 3
0
   0.0%
0
   0.0%
Leukocytes, Grade 4
0
   0.0%
0
   0.0%
Neutrophils, Grades 1 to 4
16
   4.5%
12
   3.4%
Neutrophils, Grades 2 to 4
10
   2.8%
5
   1.4%
Neutrophils, Grades 3 to 4
3
   0.8%
2
   0.6%
Neutrophils, Grade 1
6
   1.7%
7
   2.0%
Neutrophils, Grade 2
7
   2.0%
3
   0.8%
Neutrophils, Grade 3
2
   0.6%
2
   0.6%
Neutrophils, Grade 4
1
   0.3%
0
   0.0%
Platelets, Grades 1 to 4
9
   2.5%
9
   2.5%
Platelets, Grades 2 to 4
3
   0.8%
4
   1.1%
Platelets, Grades 3 to 4
0
   0.0%
1
   0.3%
Platelets, Grade 1
6
   1.7%
5
   1.4%
Platelets, Grade 2
3
   0.8%
3
   0.8%
Platelets, Grade 3
0
   0.0%
1
   0.3%
Platelets, Grade 4
0
   0.0%
0
   0.0%
13.Secondary Outcome
Title Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities
Hide Description Blood samples were collected up to Week 48 for assessment of Alanine Aminotransferase (ALT), Aspartate aminotransferase (AST), Creatinine, Glucose, Potassium, Sodium, Chloride, Calcium, Total carbon dioxide (CO2), Alkaline phosphatase (ALP), Phosphate, Total bilirubin, Total protein, Albumin, Creatine phosphokinase (CPK), Creatinine clearance,Glomerular filtration rate (GFR), Total cholesterol, High density lipoprotein (HDL), Low density lipoprotein (LDL), Triglyceride and Lipase. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent chemistry toxicities in any of the chemistry parameters have been presented.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Measure Type: Count of Participants
Unit of Measure: Participants
ALT, Grades 1 to 4
31
   8.7%
48
  13.4%
ALT, Grades 2 to 4
14
   3.9%
16
   4.5%
ALT, Grades 3 to 4
9
   2.5%
8
   2.2%
ALT, Grade 1
17
   4.8%
32
   8.9%
ALT, Grade 2
5
   1.4%
8
   2.2%
ALT, Grade 3
4
   1.1%
3
   0.8%
ALT, Grade 4
5
   1.4%
5
   1.4%
Albumin, Grades 1 to 4
1
   0.3%
1
   0.3%
Albumin, Grades 2 to 4
1
   0.3%
0
   0.0%
Albumin, Grades 3 to 4
0
   0.0%
0
   0.0%
Albumin, Grade 1
0
   0.0%
1
   0.3%
Albumin, Grade 2
1
   0.3%
0
   0.0%
Albumin, Grade 3
0
   0.0%
0
   0.0%
Albumin, Grade 4
0
   0.0%
0
   0.0%
ALP, Grades 1 to 4
7
   2.0%
7
   2.0%
ALP, Grades 2 to 4
3
   0.8%
1
   0.3%
ALP, Grades 3 to 4
0
   0.0%
0
   0.0%
ALP, Grade 1
4
   1.1%
6
   1.7%
ALP, Grade 2
3
   0.8%
1
   0.3%
ALP, Grade 3
0
   0.0%
0
   0.0%
ALP, Grade 4
0
   0.0%
0
   0.0%
AST, Grades 1 to 4
35
   9.8%
51
  14.2%
AST, Grades 2 to 4
17
   4.8%
20
   5.6%
AST, Grades 3 to 4
5
   1.4%
12
   3.4%
AST, Grade 1
18
   5.1%
31
   8.7%
AST, Grade 2
12
   3.4%
8
   2.2%
AST, Grade 3
4
   1.1%
8
   2.2%
AST, Grade 4
1
   0.3%
4
   1.1%
Bilirubin, Grades 1 to 4
28
   7.9%
37
  10.3%
Bilirubin, Grades 2 to 4
8
   2.2%
13
   3.6%
Bilirubin, Grades 3 to 4
4
   1.1%
4
   1.1%
Bilirubin, Grade 1
20
   5.6%
24
   6.7%
Bilirubin, Grade 2
4
   1.1%
9
   2.5%
Bilirubin, Grade 3
2
   0.6%
4
   1.1%
Bilirubin, Grade 4
2
   0.6%
0
   0.0%
CO2, Grades 1 to 4
99
  27.8%
81
  22.6%
CO2, Grades 2 to 4
7
   2.0%
6
   1.7%
CO2, Grades 3 to 4
0
   0.0%
0
   0.0%
CO2, Grade 1
92
  25.8%
75
  20.9%
CO2, Grade 2
7
   2.0%
6
   1.7%
CO2, Grade 3
0
   0.0%
0
   0.0%
CO2, Grade 4
0
   0.0%
0
   0.0%
Cholesterol, Grades 1 to 4
55
  15.4%
27
   7.5%
Cholesterol, Grades 2 to 4
19
   5.3%
9
   2.5%
Cholesterol, Grades 3 to 4
0
   0.0%
0
   0.0%
Cholesterol, Grade 1
36
  10.1%
18
   5.0%
Cholesterol, Grade 2
19
   5.3%
9
   2.5%
Cholesterol, Grade 3
0
   0.0%
0
   0.0%
Cholesterol, Grade 4
0
   0.0%
0
   0.0%
CPK, Grades 1 to 4
42
  11.8%
40
  11.2%
CPK, Grades 2 to 4
24
   6.7%
28
   7.8%
CPK, Grades 3 to 4
13
   3.7%
18
   5.0%
CPK, Grade 1
18
   5.1%
12
   3.4%
CPK, Grade 2
11
   3.1%
10
   2.8%
CPK, Grade 3
8
   2.2%
11
   3.1%
CPK, Grade 4
5
   1.4%
7
   2.0%
Creatinine, Grades 1 to 4
15
   4.2%
22
   6.1%
Creatinine, Grades 2 to 4
1
   0.3%
2
   0.6%
Creatinine, Grades 3 to 4
0
   0.0%
1
   0.3%
Creatinine, Grade 1
14
   3.9%
20
   5.6%
Creatinine, Grade 2
1
   0.3%
1
   0.3%
Creatinine, Grade 3
0
   0.0%
1
   0.3%
Creatinine, Grade 4
0
   0.0%
0
   0.0%
Direct Bilirubin, Grades 1 to 4
10
   2.8%
9
   2.5%
Direct Bilirubin, Grades 2 to 4
10
   2.8%
9
   2.5%
Direct Bilirubin, Grades 3 to 4
10
   2.8%
9
   2.5%
Direct Bilirubin, Grade 1
0
   0.0%
0
   0.0%
Direct Bilirubin, Grade 2
0
   0.0%
0
   0.0%
Direct Bilirubin, Grade 3
10
   2.8%
9
   2.5%
Direct Bilirubin, Grade 4
0
   0.0%
0
   0.0%
GFR, Grades 1 to 4
151
  42.4%
185
  51.7%
GFR, Grades 2 to 4
151
  42.4%
185
  51.7%
GFR, Grades 3 to 4
9
   2.5%
18
   5.0%
GFR, Grade 1
0
   0.0%
0
   0.0%
GFR, Grade 2
142
  39.9%
167
  46.6%
GFR, Grade 3
9
   2.5%
17
   4.7%
GFR, Grade 4
0
   0.0%
1
   0.3%
Hypercalcaemia, Grades 1 to 4
3
   0.8%
2
   0.6%
Hypercalcaemia, Grades 2 to 4
0
   0.0%
0
   0.0%
Hypercalcaemia, Grades 3 to 4
0
   0.0%
0
   0.0%
Hypercalcaemia, Grade 1
3
   0.8%
2
   0.6%
Hypercalcaemia, Grade 2
0
   0.0%
0
   0.0%
Hypercalcaemia, Grade 3
0
   0.0%
0
   0.0%
Hypercalcaemia, Grade 4
0
   0.0%
0
   0.0%
Hyperglycemia, Grades 1 to 4
59
  16.6%
50
  14.0%
Hyperglycemia, Grades 2 to 4
23
   6.5%
13
   3.6%
Hyperglycemia, Grades 3 to 4
3
   0.8%
2
   0.6%
Hyperglycemia, Grade 1
36
  10.1%
37
  10.3%
Hyperglycemia, Grade 2
20
   5.6%
11
   3.1%
Hyperglycemia, Grade 3
3
   0.8%
2
   0.6%
Hyperglycemia, Grade 4
0
   0.0%
0
   0.0%
Hyperkalemia, Grades 1 to 4
0
   0.0%
0
   0.0%
Hyperkalemia, Grades 2 to 4
0
   0.0%
0
   0.0%
Hyperkalemia, Grades 3 to 4
0
   0.0%
0
   0.0%
Hyperkalemia, Grade 1
0
   0.0%
0
   0.0%
Hyperkalemia, Grade 2
0
   0.0%
0
   0.0%
Hyperkalemia, Grade 3
0
   0.0%
0
   0.0%
Hyperkalemia, Grade 4
0
   0.0%
0
   0.0%
Hypernatremia, Grades 1 to 4
3
   0.8%
0
   0.0%
Hypernatremia, Grades 2 to 4
0
   0.0%
0
   0.0%
Hypernatremia, Grades 3 to 4
0
   0.0%
0
   0.0%
Hypernatremia, Grade 1
3
   0.8%
0
   0.0%
Hypernatremia, Grade 2
0
   0.0%
0
   0.0%
Hypernatremia, Grade 3
0
   0.0%
0
   0.0%
Hypernatremia, Grade 4
0
   0.0%
0
   0.0%
Hypocalcaemia, Grades 1 to 4
9
   2.5%
3
   0.8%
Hypocalcaemia, Grades 2 to 4
1
   0.3%
0
   0.0%
Hypocalcaemia, Grades 3 to 4
0
   0.0%
0
   0.0%
Hypocalcaemia, Grade 1
8
   2.2%
3
   0.8%
Hypocalcaemia, Grade 2
1
   0.3%
0
   0.0%
Hypocalcaemia, Grade 3
0
   0.0%
0
   0.0%
Hypocalcaemia, Grade 4
0
   0.0%
0
   0.0%
Hypoglycemia, Grades 1 to 4
13
   3.7%
13
   3.6%
Hypoglycemia, Grades 2 to 4
7
   2.0%
3
   0.8%
Hypoglycemia, Grades 3 to 4
2
   0.6%
1
   0.3%
Hypoglycemia, Grade 1
6
   1.7%
10
   2.8%
Hypoglycemia, Grade 2
5
   1.4%
12
   3.4%
Hypoglycemia, Grade 3
1
   0.3%
0
   0.0%
Hypoglycemia, Grade 4
1
   0.3%
1
   0.3%
Hypokalemia, Grades 1 to 4
2
   0.6%
5
   1.4%
Hypokalemia, Grades 2 to 4
0
   0.0%
1
   0.3%
Hypokalemia, Grades 3 to 4
0
   0.0%
0
   0.0%
Hypokalemia, Grade 1
2
   0.6%
4
   1.1%
Hypokalemia, Grade 2
0
   0.0%
1
   0.3%
Hypokalemia, Grade 3
0
   0.0%
0
   0.0%
Hypokalemia, Grade 4
0
   0.0%
0
   0.0%
Hyponatremia, Grades 1 to 4
19
   5.3%
21
   5.9%
Hyponatremia, Grades 2 to 4
1
   0.3%
0
   0.0%
Hyponatremia, Grades 3 to 4
0
   0.0%
0
   0.0%
Hyponatremia, Grade 1
18
   5.1%
21
   5.9%
Hyponatremia, Grade 2
1
   0.3%
0
   0.0%
Hyponatremia, Grade 3
0
   0.0%
0
   0.0%
Hyponatremia, Grade 4
0
   0.0%
0
   0.0%
LDL Cholesterol, Grades 1 to 4
41
  11.5%
25
   7.0%
LDL Cholesterol, Grades 2 to 4
14
   3.9%
10
   2.8%
LDL Cholesterol, Grades 3 to 4
5
   1.4%
3
   0.8%
LDL Cholesterol, Grade 1
27
   7.6%
15
   4.2%
LDL Cholesterol, Grade 2
9
   2.5%
7
   2.0%
LDL Cholesterol, Grade 3
5
   1.4%
3
   0.8%
LDL Cholesterol, Grade 4
0
   0.0%
0
   0.0%
Lactate Dehydrogenase, Grades 1 to 4
3
   0.8%
4
   1.1%
Lactate Dehydrogenase, Grades 2 to 4
0
   0.0%
1
   0.3%
Lactate Dehydrogenase, Grades 3 to 4
0
   0.0%
0
   0.0%
Lactate Dehydrogenase, Grade 1
3
   0.8%
3
   0.8%
Lactate Dehydrogenase, Grade 2
0
   0.0%
1
   0.3%
Lactate Dehydrogenase, Grade 3
0
   0.0%
0
   0.0%
Lactate Dehydrogenase, Grade 4
0
   0.0%
0
   0.0%
Lipase, Grades 1 to 4
41
  11.5%
50
  14.0%
Lipase, Grades 2 to 4
23
   6.5%
25
   7.0%
Lipase, Grades 3 to 4
5
   1.4%
9
   2.5%
Lipase, Grade 1
18
   5.1%
25
   7.0%
Lipase, Grade 2
18
   5.1%
16
   4.5%
Lipase, Grade 3
4
   1.1%
4
   1.1%
Lipase, Grade 4
1
   0.3%
5
   1.4%
Phosphate, Grades 1 to 4
40
  11.2%
47
  13.1%
Phosphate, Grades 2 to 4
19
   5.3%
31
   8.7%
Phosphate, Grades 3 to 4
1
   0.3%
3
   0.8%
Phosphate, Grade 1
21
   5.9%
16
   4.5%
Phosphate, Grade 2
18
   5.1%
28
   7.8%
Phosphate, Grade 3
1
   0.3%
3
   0.8%
Phosphate, Grade 4
0
   0.0%
0
   0.0%
Triglycerides, Grades 1 to 4
56
  15.7%
44
  12.3%
Triglycerides, Grades 2 to 4
11
   3.1%
10
   2.8%
Triglycerides, Grades 3 to 4
6
   1.7%
3
   0.8%
Triglycerides, Grade 1
45
  12.6%
34
   9.5%
Triglycerides, Grade 2
5
   1.4%
7
   2.0%
Triglycerides, Grade 3
5
   1.4%
2
   0.6%
Triglycerides, Grade 4
1
   0.3%
1
   0.3%
14.Secondary Outcome
Title Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48
Hide 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. Data cut-off dates for analysis at Week 24 and Week 48 were 19-Jan-2018 and 22-May-2018 respectively. Number of participants who discontinued treatment due to AEs have been reported.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Measure Type: Count of Participants
Unit of Measure: Participants
Up to Week 24
6
   1.7%
4
   1.1%
Up to Week 48
7
   2.0%
8
   2.2%
15.Secondary Outcome
Title Change From Baseline in Renal Biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48
Hide Description Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers which included Serum Cystatin C and Serum Retinol Binding Protein (RBP). Baseline value is the latest pre-dose assessment. Change from Baseline was defined as post-dose visit value minus Baseline value. 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), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
Time Frame Baseline and at Weeks 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Mean (Standard Error)
Unit of Measure: Milligrams per Liter (mg/L)
Serum Cystatin C, Week 24, n=338, 336 Number Analyzed 338 participants 336 participants
-0.05  (0.007) -0.03  (0.007)
Serum Cystatin C, Week 48, n=324, 332 Number Analyzed 324 participants 332 participants
-0.07  (0.007) -0.04  (0.006)
Serum RBP, Week 24, n=332, 334 Number Analyzed 332 participants 334 participants
1.6  (0.41) 1.9  (0.51)
Serum RBP, Week 48, n=322, 332 Number Analyzed 322 participants 332 participants
0.5  (0.47) 0.6  (0.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.025
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.04 to 0.00
Estimation Comments Serum Cystatin C, Week 24
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.05 to -0.01
Estimation Comments Serum Cystatin C, Week 48
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.683
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-1.6 to 1.0
Estimation Comments Serum RBP, Week 24
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.930
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-1.4 to 1.2
Estimation Comments Serum RBP, Week 48
16.Secondary Outcome
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
Hide Description Blood and/or urine 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 post-dose visit value minus Baseline value. 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), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
Time Frame Baseline and at Weeks 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Mean (Standard Error)
Unit of Measure: Milliliter/minute/1.73*meter^2
GFR-cystatin C adjusted, Week 24, n=338, 336 Number Analyzed 338 participants 336 participants
4.4  (0.63) 2.2  (0.60)
GFR-cystatin C adjusted, Week 48, n=324, 332 Number Analyzed 324 participants 332 participants
7.0  (0.60) 4.1  (0.59)
GFR-creatinine adjusted, Week 24, n=340, 341 Number Analyzed 340 participants 341 participants
-13.5  (0.59) -16.7  (0.56)
GFR-creatinine adjusted, Week 48, n=326,335 Number Analyzed 326 participants 335 participants
-12.1  (0.56) -15.6  (0.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
0.5 to 4.0
Estimation Comments GFR-cystatin C adjusted, Week 24
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
1.2 to 4.5
Estimation Comments GFR-cystatin C adjusted, Week 48
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
1.6 to 4.8
Estimation Comments GFR-creatinine adjusted, Week 24
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.5
Confidence Interval (2-Sided) 95%
2.0 to 5.1
Estimation Comments GFR- creatinine adjusted, Week 48
17.Secondary Outcome
Title Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Weeks 24, 48
Hide Description Blood and/or urine were collected to perform evaluation of renal inflammation biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as post-dose visit value minus Baseline value. 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), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
Time Frame Baseline and at Weeks 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Mean (Standard Error)
Unit of Measure: Micromoles per Liter (umol/L)
Serum or Plasma Creatinine, Week 24, n=340, 343 Number Analyzed 340 participants 343 participants
11.88  (0.510) 15.07  (0.520)
Serum or Plasma Creatinine, Week 48, n=326, 335 Number Analyzed 326 participants 335 participants
10.39  (0.466) 13.61  (0.480)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.19
Confidence Interval (2-Sided) 95%
-4.62 to -1.75
Estimation Comments Week 24
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.22
Confidence Interval (2-Sided) 95%
-4.54 to -1.91
Estimation Comments Week 48
18.Secondary Outcome
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
Hide Description Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers which included 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 is defined as the latest pre-dose assessment. Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Statistical analysis of changes from baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios. Estimated ratio of geometric means (each visit over Baseline) and 95% confidence interval (CI) have been presented.
Time Frame Baseline and at Weeks 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
Serum B2M, Week 24, n=338, 335 Number Analyzed 338 participants 335 participants
0.798
(0.779 to 0.817)
0.872
(0.856 to 0.890)
Serum B2M, Week 48, n=324, 332 Number Analyzed 324 participants 332 participants
0.806
(0.790 to 0.823)
0.892
(0.876 to 0.908)
Urine B2M, Week 24, n=121, 95 Number Analyzed 121 participants 95 participants
0.887
(0.756 to 1.039)
1.351
(1.060 to 1.722)
Urine B2M, Week 48, n=119, 103 Number Analyzed 119 participants 103 participants
0.900
(0.792 to 1.022)
1.338
(1.148 to 1.560)
Urine Albumin/Creatinine, Week 24, n=254, 252 Number Analyzed 254 participants 252 participants
1.014
(0.927 to 1.109)
1.050
(0.964 to 1.144)
Urine Albumin/Creatinine , Week 48, n=237, 244 Number Analyzed 237 participants 244 participants
0.934
(0.857 to 1.017)
1.048
(0.968 to 1.134)
Urine B2M/Urine Creatinine , Week 24, n=121, 95 Number Analyzed 121 participants 95 participants
0.852
(0.737 to 0.985)
1.331
(1.071 to 1.655)
Urine B2M/Urine Creatinine , Week 48, n=114, 100 Number Analyzed 114 participants 100 participants
0.888
(0.777 to 1.015)
1.278
(1.119 to 1.458)
Urine Phosphate, Week 24, n=330, 332 Number Analyzed 330 participants 332 participants
1.115
(1.025 to 1.212)
1.012
(0.934 to 1.095)
Urine Phosphate , Week 48, n=316, 330 Number Analyzed 316 participants 330 participants
1.061
(0.983 to 1.145)
1.075
(0.996 to 1.159)
Urine Protein/Creatinine , Week 24, n=269, 265 Number Analyzed 269 participants 265 participants
0.850
(0.806 to 0.895)
1.016
(0.960 to 1.075)
Urine Protein/Creatinine , Week 48, n=252, 269 Number Analyzed 252 participants 269 participants
0.879
(0.838 to 0.922)
1.061
(1.009 to 1.115)
Urine RBP 4, Week 24, n=332, 330 Number Analyzed 332 participants 330 participants
0.934
(0.842 to 1.036)
1.073
(0.951 to 1.209)
Urine RBP 4, Week 48, n=318, 328 Number Analyzed 318 participants 328 participants
1.115
(1.009 to 1.233)
1.490
(1.332 to 1.667)
Urine RBP 4/Urine Creatinine , Week 24, n=329, 330 Number Analyzed 329 participants 330 participants
0.919
(0.846 to 0.998)
1.110
(1.003 to 1.228)
Urine RBP 4/Urine Creatinine , Week 48, n=304, 318 Number Analyzed 304 participants 318 participants
1.147
(1.060 to 1.241)
1.500
(1.367 to 1.646)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.915
Confidence Interval (2-Sided) 95%
0.887 to 0.943
Estimation Comments Week 24. Serum B2M
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.904
Confidence Interval (2-Sided) 95%
0.880 to 0.929
Estimation Comments Week 48. Serum B2M
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.656
Confidence Interval (2-Sided) 95%
0.491 to 0.877
Estimation Comments Week 24. Urine B2M
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.672
Confidence Interval (2-Sided) 95%
0.551 to 0.821
Estimation Comments Week 48. Urine B2M
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.575
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.965
Confidence Interval (2-Sided) 95%
0.853 to 1.092
Estimation Comments Week 24. Urine Albumin/Creatinine
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.051
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.891
Confidence Interval (2-Sided) 95%
0.793 to 1.001
Estimation Comments Week 48. Urine Albumin/Creatinine
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.640
Confidence Interval (2-Sided) 95%
0.493 to 0.831
Estimation Comments Week 24. Urine B2M/Urine Creatinine
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.695
Confidence Interval (2-Sided) 95%
0.576 to 0.839
Estimation Comments Week 48. Urine B2M/Urine Creatinine
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.099
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 1.102
Confidence Interval (2-Sided) 95%
0.982 to 1.237
Estimation Comments Week 24. Urine Phosphate
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.816
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.987
Confidence Interval (2-Sided) 95%
0.886 to 1.100
Estimation Comments Week 48. Urine Phosphate
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.836
Confidence Interval (2-Sided) 95%
0.774 to 0.904
Estimation Comments Week 24. Urine Protein/Creatinine
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.829
Confidence Interval (2-Sided) 95%
0.773 to 0.888
Estimation Comments Week 48. Urine Protein/Creatinine
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.087
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.871
Confidence Interval (2-Sided) 95%
0.743 to 1.020
Estimation Comments Week 24. Urine RBP 4
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.748
Confidence Interval (2-Sided) 95%
0.644 to 0.870
Estimation Comments Week 48. Urine RBP 4
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.828
Confidence Interval (2-Sided) 95%
0.727 to 0.944
Estimation Comments Week 24. Urine RBP 4/Urine Creatinine
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 0.765
Confidence Interval (2-Sided) 95%
0.677 to 0.864
Estimation Comments Week 48. Urine RBP 4/Urine Creatinine
19.Secondary Outcome
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
Hide Description Blood samples were collected to perform evaluation of bone biomarkers which included bone-ALP, Serum Osteocalcin, PINP and CTX-1. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as post-dose visit value minus Baseline value. 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.
Time Frame Baseline and at Weeks 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Mean (Standard Error)
Unit of Measure: Micrograms per Liter (ug/L)
Bone-ALP, Week 24, n=334, 332 Number Analyzed 334 participants 332 participants
0.91  (0.179) 3.13  (0.199)
Bone-ALP, Week 48, n=321, 331 Number Analyzed 321 participants 331 participants
1.21  (0.193) 3.79  (0.239)
Serum Osteocalcin, Week 24, n=335, 334 Number Analyzed 335 participants 334 participants
2.56  (0.341) 6.74  (0.347)
Serum Osteocalcin, Week 48, n=322, 330 Number Analyzed 322 participants 330 participants
0.78  (0.311) 6.01  (0.400)
PINP, Week 24, n=337, 336 Number Analyzed 337 participants 336 participants
4.5  (0.91) 18.3  (1.06)
PINP, Week 48, n=321, 334 Number Analyzed 321 participants 334 participants
0.5  (0.83) 13.1  (0.84)
CTX-1, Week 24, n=337, 334 Number Analyzed 337 participants 334 participants
0.1192  (0.01304) 0.2820  (0.01472)
CTX-1, Week 48, n=323, 331 Number Analyzed 323 participants 331 participants
0.1338  (0.01258) 0.3352  (0.01885)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.23
Confidence Interval (2-Sided) 95%
-2.75 to -1.70
Estimation Comments Week 24. Bone ALP
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.58
Confidence Interval (2-Sided) 95%
-3.19 to -1.98
Estimation Comments Week 48. Bone ALP
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.19
Confidence Interval (2-Sided) 95%
-5.15 to -3.23
Estimation Comments Week 28. Serum Osteocalcin
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.23
Confidence Interval (2-Sided) 95%
-6.22 to -4.23
Estimation Comments Week 48. Serum Osteocalcin
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -13.8
Confidence Interval (2-Sided) 95%
-16.5 to -11.1
Estimation Comments Week 24. Serum PINP
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -12.6
Confidence Interval (2-Sided) 95%
-15.0 to -10.3
Estimation Comments Week 48. Serum PINP
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1628
Confidence Interval (2-Sided) 95%
-0.2015 to -0.1241
Estimation Comments Week 24. CTX-1
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2015
Confidence Interval (2-Sided) 95%
-0.2460 to -0.1569
Estimation Comments Week 48. CTX-1
20.Secondary Outcome
Title Change From Baseline in Bone Biomarker-Serum Vitamin D at Weeks 24, 48
Hide Description Blood samples were collected to perform evaluation of bone biomarker serum vitamin D. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as post-dose visit value minus Baseline value. 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.
Time Frame Baseline and at Weeks 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Mean (Standard Error)
Unit of Measure: Nanomoles per Liter (nmol/L)
Serum Vitamin D, Week 24, n=337, 337 Number Analyzed 337 participants 337 participants
5.9  (1.15) 12.4  (1.33)
Serum Vitamin D, Week 48, n=322, 333 Number Analyzed 322 participants 333 participants
-3.1  (0.89) 3.1  (1.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -6.5
Confidence Interval (2-Sided) 95%
-9.9 to -3.0
Estimation Comments Week 24
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -6.2
Confidence Interval (2-Sided) 95%
-9.0 to -3.4
Estimation Comments Week 48
21.Secondary Outcome
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
Hide 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).
Time Frame Baseline (Day 1) and at Weeks 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Mean (Standard Deviation)
Unit of Measure: Percentage change
Serum or Plasma Cholesterol, Week 24, n=294, 297 Number Analyzed 294 participants 297 participants
9.4  (17.44) -4.7  (16.12)
Serum or Plasma Cholesterol, Week 48, n=280, 289 Number Analyzed 280 participants 289 participants
10.5  (18.89) -2.4  (17.14)
HDL Cholesterol, Direct, Week 24, n=294, 297 Number Analyzed 294 participants 297 participants
16.4  (22.58) 3.4  (21.55)
HDL Cholesterol, Direct, Week 48, n=280, 289 Number Analyzed 280 participants 289 participants
15.0  (25.07) 5.0  (33.04)
LDL Cholesterol, Week 24, n=294, 297 Number Analyzed 294 participants 297 participants
12.4  (45.05) -8.1  (23.70)
LDL Cholesterol, Week 48, n=280, 289 Number Analyzed 280 participants 289 participants
14.8  (48.74) -4.0  (24.06)
Triglycerides ,Week 24, n=294, 297 Number Analyzed 294 participants 297 participants
8.5  (46.57) 4.3  (72.35)
Triglycerides , Week 48, n=280, 289 Number Analyzed 280 participants 289 participants
12.8  (68.99) 4.4  (70.43)
22.Secondary Outcome
Title Percentage Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48
Hide Description Blood samples were collected to perform evaluation of fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio. Baseline value is 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).
Time Frame Baseline (Day 1) and at Weeks 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Mean (Standard Deviation)
Unit of Measure: Percentage change
Total/HDL Cholesterol Ratio, Week 24, n=294, 297 Number Analyzed 294 participants 297 participants
-4.0  (19.08) -4.6  (27.52)
Total/HDL Cholesterol Ratio, Week 48, n=280, 289 Number Analyzed 280 participants 289 participants
-0.2  (31.10) -4.4  (16.96)
23.Secondary Outcome
Title Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Weeks 24, 48
Hide 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). The higher the grade, the more severe the symptoms. 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 are 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.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Measure Type: Number
Unit of Measure: Percentage of participants
Week 24, n=309, 316 Number Analyzed 309 participants 316 participants
4 2
Week 48, n=318, 320 Number Analyzed 318 participants 320 participants
4 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.157
Comments Fisher's exact p-value.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-0.6 to 4.6
Estimation Comments Week 24
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.414
Comments Fisher's exact p-value.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-1.7 to 4.2
Estimation Comments Week 48
24.Secondary Outcome
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
Hide 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 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. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200, >200), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian, Other).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Measure Type: Number
Unit of Measure: Percentage of participants
Baseline CD4+ cell count, <=200,n=31,29 Number Analyzed 31 participants 29 participants
90 86
Baseline CD4+ cell count, >200,n=325,329 Number Analyzed 325 participants 329 participants
93 94
Female, n=59, 52 Number Analyzed 59 participants 52 participants
93 96
Male, n=297, 306 Number Analyzed 297 participants 306 participants
92 92
Age, <35,n= 211, 205 Number Analyzed 211 participants 205 participants
93 95
Age, 35 to <50,n=116, 107 Number Analyzed 116 participants 107 participants
91 93
Age, >=50, n=29, 46 Number Analyzed 29 participants 46 participants
93 85
Baseline plasma HIV-1 RNA, <=100000,n=282,282 Number Analyzed 282 participants 282 participants
93 95
Baseline plasma HIV-1 RNA, >100000,n=74, 76 Number Analyzed 74 participants 76 participants
92 87
Race, White, n=243,248 Number Analyzed 243 participants 248 participants
93 95
Race, African American/African H., n=44, 36 Number Analyzed 44 participants 36 participants
93 81
Race, Asian, n=37, 42 Number Analyzed 37 participants 42 participants
89 93
Race, Other, n=32, 32 Number Analyzed 32 participants 32 participants
94 94
25.Secondary Outcome
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
Hide 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 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. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200, >200), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian, Other).
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Measure Type: Number
Unit of Measure: Percentage of participants
Baseline CD4+ cell count, <=200,n=31,29 Number Analyzed 31 participants 29 participants
81 90
Baseline CD4+ cell count, >200,n=325,329 Number Analyzed 325 participants 329 participants
91 93
Female, n=59, 52 Number Analyzed 59 participants 52 participants
88 94
Male, n=297, 306 Number Analyzed 297 participants 306 participants
90 92
Age, <35,n= 211, 205 Number Analyzed 211 participants 205 participants
92 93
Age, 35 to <50,n=116, 107 Number Analyzed 116 participants 107 participants
86 94
Age, >=50, n=29, 46 Number Analyzed 29 participants 46 participants
90 87
Baseline plasma HIV-1 RNA, <=100000,n=282,282 Number Analyzed 282 participants 282 participants
90 93
Baseline plasma HIV-1 RNA, >100000,n=74, 76 Number Analyzed 74 participants 76 participants
88 91
Race, White, n=243,248 Number Analyzed 243 participants 248 participants
90 94
Race, African American/African H., n=44, 36 Number Analyzed 44 participants 36 participants
89 81
Race, Asian, n=37, 42 Number Analyzed 37 participants 42 participants
92 98
Race, Other, n=32, 32 Number Analyzed 32 participants 32 participants
88 94
26.Secondary Outcome
Title Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups
Hide 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 latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value 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.
Time Frame Baseline (Day 1) and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Mean (Standard Error)
Unit of Measure: Cells per cubic millimeter
Baseline plasma HIV-1 RNA,<=100000, n=257,264 Number Analyzed 257 participants 264 participants
220.0  (11.72) 212.4  (11.56)
Baseline plasma HIV-1 RNA,>100000, n=67,70 Number Analyzed 67 participants 70 participants
238.5  (23.09) 235.5  (22.70)
Baseline CD4+ cell count,<=200, n=26, 27 Number Analyzed 26 participants 27 participants
200.5  (36.97) 177.9  (36.18)
Baseline CD4+ cell count,>200, n=298, 307 Number Analyzed 298 participants 307 participants
225.9  (10.84) 220.7  (10.68)
Age group-1, <35,n= 194, 192 Number Analyzed 194 participants 192 participants
233.6  (13.49) 225.2  (13.53)
Age group-1, 35 to <50, n=104, 101 Number Analyzed 104 participants 101 participants
208.7  (18.40) 211.2  (18.67)
Age group-1, >=50, n=26, 41 Number Analyzed 26 participants 41 participants
212.6  (36.84) 194.8  (29.27)
Female, n=54, 49 Number Analyzed 54 participants 49 participants
237.1  (25.53) 226.8  (26.98)
Male, n=270, 285 Number Analyzed 270 participants 285 participants
221.2  (11.41) 215.6  (11.11)
Race, White, n=223, 232 Number Analyzed 223 participants 232 participants
226.0  (12.58) 219.9  (12.37)
Race, African Am/African H., n=38, 31 Number Analyzed 38 participants 31 participants
209.4  (30.54) 232.5  (33.79)
Race, Asian, n=34, 41 Number Analyzed 34 participants 41 participants
246.4  (32.36) 197.2  (29.48)
Race, Other, n=29, 30 Number Analyzed 29 participants 30 participants
200.0  (34.91) 208.1  (34.39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 7.6
Confidence Interval (2-Sided) 95%
-24.6 to 39.8
Estimation Comments Baseline plasma HIV-1 RNA,<=100000. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count and treatment and HIV-1 RNA interaction.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.0
Confidence Interval (2-Sided) 95%
-59.8 to 65.9
Estimation Comments Baseline plasma HIV-1 RNA,>100000. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count and treatment and HIV-1 RNA interaction.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 22.6
Confidence Interval (2-Sided) 95%
-78.3 to 123.5
Estimation Comments 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.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 5.2
Confidence Interval (2-Sided) 95%
-24.7 to 35.1
Estimation Comments 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.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.4
Confidence Interval (2-Sided) 95%
-29.1 to 45.9
Estimation Comments Age<35. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-53.9 to 48.9
Estimation Comments Age 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.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 17.7
Confidence Interval (2-Sided) 95%
-74.6 to 110.1
Estimation Comments Age>=50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 10.4
Confidence Interval (2-Sided) 95%
-62.3 to 83.1
Estimation Comments Female. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 5.6
Confidence Interval (2-Sided) 95%
-25.6 to 36.9
Estimation Comments Male. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.1
Confidence Interval (2-Sided) 95%
-28.5 to 40.7
Estimation Comments Race group white. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race group, and treatment and race group interaction.
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -23.0
Confidence Interval (2-Sided) 95%
-112.6 to 66.6
Estimation Comments Race group African Am/African H.. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race group, and treatment and race group interaction.
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 49.2
Confidence Interval (2-Sided) 95%
-36.3 to 134.7
Estimation Comments Race group Asian. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race group, and treatment and race group interaction.
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection DTG + 3TC, DTG + TDF/FTC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -8.1
Confidence Interval (2-Sided) 95%
-104.1 to 87.9
Estimation Comments Race group Other. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race group, and treatment and race group interaction.
27.Secondary Outcome
Title Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups
Hide 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 latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age, 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.
Time Frame Baseline (Day 1) and Week 24
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Hide Analysis Population Description
ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title DTG + 3TC DTG + TDF/FTC
Hide Arm/Group Description:
Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.
Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Overall Number of Participants Analyzed 356 358
Mean (Standard Error)
Unit of Measure: Cells per cubic millimeter
Baseline plasma HIV-1 RNA,<=100000, n=268,268 Number Analyzed 268 participants 268 participants
187.72  (10.860) 167.93  (10.842)
Baseline plasma HIV-1 RNA,>100000, n=72,73 Number Analyzed 72 participants 73 participants
206.63  (21.107) 205.96  (20.990)
Baseline CD4+ cell count,<=200, n=29,27 Number Analyzed 29 participants 27 participants
157.01  (33.113) 120.17  (34.151)
Baseline CD4+ cell count,>200, n=311, 314 Number Analyzed 311 participants 314 participants
195.11  (10.026) 180.73  (9.972)
Age, <35,n= 203,199 Number Analyzed 203 participants 199 participants
202.76  (12.456) 177.62  (12.563)
Age, 35 to <50, n=109, 100 Number Analyzed 109 participants 100 participants
172.05  (16.983) 179.87  (17.733)
Age, >=50, n=28, 42 Number Analyzed 28 participants 42 participants
188.79  (33.534) 159.34  (27.344)
Female, n=57,50 Number Analyzed 57 participants 50 participants
199.45  (23.498) 181.78  (25.263)
Male, n=283,291 Number Analyzed 283 participants 291 participants
190.21  (10.538) 175.05  (10.400)
Race, White, n=235,236 Number Analyzed 235 participants 236 participants
204.36  (11.561) 180.49  (11.559)
Race, African Am/African H., n=41,33 Number Analyzed 41 participants 33 participants
147.04  (27.706) 180.96  (30.880)
Race, Asian, n=34, 41 Number Analyzed 34 participants 41 participants
169.92  (30.502) 165.46  (27.793)