A Study to Determine Safety and Efficacy of Dolutegravir/Abacavir/Lamivudine (DTG/ABC/3TC) in Human Immunodeficiency Virus (HIV)-1 Infected Antiretroviral Therapy (ART) Naïve Women (ARIA)

A Phase IIIb, Randomized, Open-label Study of the Safety and Efficacy of Dolutegravir/Abacavir/Lamivudine Once Daily Compared to Atazanavir and Ritonavir Plus Tenofovir/Emtricitabine Once Daily in HIV-1 Infected Antiretroviral Therapy Naïve Women

This study is designed to demonstrate the non-inferior antiviral activity of DTG/ABC/3TC fixed dose combination (FDC) once daily (OD) compared to atazanavir plus ritonavir (ATV+RTV) and tenofovir disoproxil fumarate/emtricitabine fixed dose combination (TDF/FTC FDC) OD in HIV-1 infected, ART-naïve women over 48 weeks. This study will also characterize the safety and tolerability of DTG/ABC/3TC FDC compared to ATV+RTV+TDF/FTC FDC. Sufficient number of subjects will be screened in order to ensure a total of approximately 474 subjects will be randomized (237 in each study arm)

Study Overview

• Status: Completed
• Conditions: HIV Infections; Infection, Human Immunodeficiency Virus
• Intervention / Treatment: Drug: Dolutegravir/abacavir/lamivudine FDC; Drug: Atazanavir; Drug: Ritonavir; Drug: Tenofovir/emtricitabine FDC

• Study Type: Interventional
• Enrollment (Actual): 499
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1141
    • GSK Investigational Site
  • Buenos Aires
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1405CKC
      • GSK Investigational Site
    • Ciudad de Buenos Aires, Buenos Aires, Argentina, C1202ABB
      • GSK Investigational Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • GSK Investigational Site
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M4N 3M5
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5G 2N2
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 2P4
      • GSK Investigational Site
• France
  • Bobigny, France, 93009
    • GSK Investigational Site
  • Nantes, France, 44093
    • GSK Investigational Site
  • Paris Cedex 10, France, 75475
    • GSK Investigational Site
• Italy
  • Liguria
    • Genova, Liguria, Italy, 16128
      • GSK Investigational Site
  • Lombardia
    • Bergamo, Lombardia, Italy, 24127
      • GSK Investigational Site
    • Brescia, Lombardia, Italy, 25123
      • GSK Investigational Site
    • Busto Arsizio (VA), Lombardia, Italy, 21052
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20127
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20157
      • GSK Investigational Site
  • Piemonte
    • Torino, Piemonte, Italy, 10149
      • GSK Investigational Site
• Mexico
  • Mexico, Mexico, 14000
    • GSK Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • GSK Investigational Site
• Portugal
  • Amadora, Portugal, 2720-276
    • GSK Investigational Site
  • Lisboa, Portugal, 1150
    • GSK Investigational Site
  • Porto, Portugal, 4200-319
    • GSK Investigational Site
• Puerto Rico
  • Ponce, Puerto Rico, 00717
    • GSK Investigational Site
  • Rio Piedras, Puerto Rico, 00936
    • GSK Investigational Site
  • San Juan, Puerto Rico, 00909
    • GSK Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 115035
    • GSK Investigational Site
  • Orel, Russian Federation, 302040
    • GSK Investigational Site
  • Smolensk, Russian Federation, 214006
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 196645
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 190103
    • GSK Investigational Site
  • Toliyatti, Russian Federation, 445846
    • GSK Investigational Site
• South Africa
  • Mamelodi East, South Africa, 122
    • GSK Investigational Site
  • Western Province
    • Observatory, Cape Town, Western Province, South Africa, 7925
      • GSK Investigational Site
• Spain
  • (Móstoles) Madrid, Spain, 28935
    • GSK Investigational Site
  • Alicante, Spain, 03010
    • GSK Investigational Site
  • Badalona, Spain, 08916
    • GSK Investigational Site
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Barcelona, Spain, 08907
    • GSK Investigational Site
  • Granada, Spain, 18012
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
  • Madrid, Spain, 28034
    • GSK Investigational Site
  • Malaga, Spain, 29010
    • GSK Investigational Site
  • Murcia, Spain, 30003
    • GSK Investigational Site
  • Sevilla, Spain, 41013
    • GSK Investigational Site
• Thailand
  • Bangkok, Thailand, 10330
    • GSK Investigational Site
  • Nonthaburi, Thailand, 11000
    • GSK Investigational Site
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • GSK Investigational Site
  • London, United Kingdom, E1 1BB
    • GSK Investigational Site
  • London, United Kingdom, NW3 2QG
    • GSK Investigational Site
  • London, United Kingdom, W2 1NY
    • GSK Investigational Site
  • Sheffield, United Kingdom, S10 2JF
    • GSK Investigational Site
  • Tooting, London, United Kingdom, SW17 0QT
    • GSK Investigational Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85015
      • GSK Investigational Site
  • California
    • Bakersfield, California, United States, 93301
      • GSK Investigational Site
    • Beverly Hills, California, United States, 90211
      • GSK Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • GSK Investigational Site
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • GSK Investigational Site
    • Miami, Florida, United States, 33133
      • GSK Investigational Site
    • Orlando, Florida, United States, 32803
      • GSK Investigational Site
    • Tampa, Florida, United States, 33602
      • GSK Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • GSK Investigational Site
    • Augusta, Georgia, United States, 30912-3130
      • GSK Investigational Site
    • Decatur, Georgia, United States, 30033
      • GSK Investigational Site
    • Savannah, Georgia, United States, 31401
      • GSK Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • GSK Investigational Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • GSK Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • GSK Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • GSK Investigational Site
    • Saint Louis, Missouri, United States, 63110
      • GSK Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • GSK Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • GSK Investigational Site
  • New Jersey
    • Neptune, New Jersey, United States, 7754
      • GSK Investigational Site
    • Newark, New Jersey, United States, 07103
      • GSK Investigational Site
  • New York
    • Buffalo, New York, United States, 14215
      • GSK Investigational Site
    • Valhalla, New York, United States, 10595
      • GSK Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • GSK Investigational Site
    • Charlotte, North Carolina, United States, 28207
      • GSK Investigational Site
    • Greensboro, North Carolina, United States, 27401-1209
      • GSK Investigational Site
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18102
      • GSK Investigational Site
    • Philadelphia, Pennsylvania, United States, 19107
      • GSK Investigational Site
    • Philadelphia, Pennsylvania, United States, 19140
      • GSK Investigational Site
    • Philadelphia, Pennsylvania, United States, 19104
      • GSK Investigational Site
  • Texas
    • Bellaire, Texas, United States, 77401
      • GSK Investigational Site
    • Dallas, Texas, United States, 75246
      • GSK Investigational Site
    • Dallas, Texas, United States, 75235
      • GSK Investigational Site
    • El Paso, Texas, United States, 79905
      • GSK Investigational Site
    • Fort Worth, Texas, United States, 76104
      • GSK Investigational Site
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• HIV-1 infected females (gender at birth) >=18 years of age
• Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol)
• HIV-1 infection as documented by Screening plasma HIV-1 RNA >=500 c/mL.
• Documentation that the subject is negative for the HLA-B*5701 allele.
• Antiretroviral-naïve (<=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection).
• Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening.

Exclusion Criteria:

• Women who are pregnant or breastfeeding
• Women who plan to become pregnant during the first 48 weeks of the study
• Any subject who has had a medical intervention for gender reassignment
• Any evidence of an active Centers for Disease Control and Prevention (CDC) Category C disease
• Subjects with any degree of hepatic impairment
• Subjects positive for hepatitis B at Screening, or anticipated need for HCV therapy during the study
• History or presence of allergy to the study drugs or their components or drugs of their class
• Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia
• poses a significant suicidality risk
• History of osteoporosis with fracture or requiring pharmacologic therapy
• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
• Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses;
• Treatment with any agent, with documented activity against HIV-1 in vitro within 28 days of first dose of investigational product (IP)
• Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of IP
• Any evidence of primary viral resistance based on the presence of any major resistance-associated mutation in the Screening result or, if known, any historical resistance test result
• Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities (total cholesterol, triglycerides, High Density Lipoprotein (HDL) cholesterol, Low Density Lipoprotein (LDL) cholesterol)
• Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound
• Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), or ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin)
• Subject has CrCL of <50 mL/min via Cockroft-Gault method
• Corrected QT interval (QTc (Bazett)) ≥450msec or QTc (Bazett) ≥480msec for subjects with bundle branch block.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DTG/ABC/3TC FDC; As per the randomization schedule subjects will be administered with DTG/ABC/3TC (50mg/600mg/300mg) FDC tablet OD up to Week 48 and if continued if applicable in the Continuation Phase. DTG/ABC/3TC FDC may be administered with or without food	Drug: Dolutegravir/abacavir/lamivudine FDC; Dolutegravir/abacavir/lamivudine FDC tablets, 50 mg/600 mg/300 mg
Active Comparator: ATV +RTV +TDF/FTC FDC; As per the randomization schedule subjects will be administered with ATV (300mg capsule) +RTV (100mg tablet) + TDF/FTC (300mg/200mg tablet) FDC OD up to Week 48. ATV+RTV+ TDF/FTC FDC must be taken with food	Drug: Atazanavir; Atazanavir capsule 300 mg; Drug: Ritonavir; Ritonavir tablet 100 mg; Drug: Tenofovir/emtricitabine FDC; Tenofovir/emtricitabine FDC tablet 300 mg/200 mg of FTC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 48	Percentage of participants with plasma human immunodeficiency virus type 1(HIV-1) ribonucleic acid (RNA) <50 copies per milliliter (c/mL) were assessed at Week 48 using the Snapshot algorithm. Analysis was performed using a stratified analysis with Cochran-Mantel-Haenszel (CMH) weights, adjusting for Baseline plasma HIV-1 RNA ( =<vs. >100,000 c/mL) and CD4+ cell count (=<350 cells per millimeter cube (cells/mm^3) or >350 cells/mm^3). Intent-to-Treat Exposed (ITT-E) Population comprised of all randomized participants who received at least one dose of study medication. Percentage values are rounded off.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Plasma HIV-1 RNA <50 and <400 c/mL Over Time-Randomized Phase	Percentage of participants with plasma HIV-1 RNA <50 and <400 c/mL were assessed at Baseline, Weeks 4, 12, 24 , 36 and 48 using the Snapshot algorithm (Missing, Switch or Discontinuation = Failure). The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Percentage values are rounded off.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL in Continuation Phase	Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with plasma HIV-1 RNA <50 c/mL were reported. Percentage values are rounded off.	Week 96 and Week 432
Change From Baseline in Plasma HIV-1 RNA at Indicated Time Points-Randomized Phase	Change from the Baseline in plasma HIV-1 RNA were assessed at indicated time points. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Plasma HIV-1 RNA at Indicated Time Points-Continuation Phase	Change from the Baseline in plasma HIV-1 RNA were assessed at indicated time points. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 96 and Week 432
Absolute Values in Plasma HIV-1 RNA at Indicated Time Points-Randomized Phase	Absolute Values in plasma HIV-1 RNA were assessed at indicated time points. The Baseline value was defined as the latest pre-dose assessment (Day 1) value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Absolute Values in Plasma HIV-1 RNA at Indicated Time Points-Continuation Phase	Absolute Values in plasma HIV-1 RNA were assessed at indicated time points.	Week 96 and Week 432
Change From Baseline in CD4+ Cell Count at Indicated Timepoints-Randomized Phase	Change from Baseline in cluster of differentiation 4 (CD4+) cell count were assessed at indicated time points. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in CD4+ Cell Count at Indicated Timepoints-Continuation Phase	Change from Baseline in cluster of differentiation 4(CD4+) cell count were assessed at indicated time points. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 96, Week 432
Absolute Values in CD4+ Cell Count at Indicated Timepoints-Randomized Phase	Absolute values in CD4+ cell count were assessed at indicated time points. The Baseline value was defined as the latest pre-dose assessment (Day 1) value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Absolute Values in CD4+ Cell Count at Indicated Timepoints-Continuation Phase	Absolute values in CD4+ cell count were assessed at indicated time points.	Week 96 and Week 432
Change From Baseline in Carbon Dioxide, Electrolytes, Lipids, Glucose, Urea at Indicated Time Points	Clinical chemistry parameters were assessed at Baseline (Day 1), Weeks 4, 12, 24, 36 and 48. Change from Baseline in carbon dioxide, electrolytes (chloride, hyperkalemia, hypernatremia, hypokalemia, hyponatremia, phosphate, potassium, sodium), lipids (cholesterol [CHLS], high density lipoprotein [HDL] CHLS direct, low density lipoprotein (LDL) CHLS calculation, LDL CHLS direct, triglycerides), glucose (hyperglycaemia, hypoglycaemia) and urea are summarized. Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value. Laboratory parameters were assessed in Safety Population which comprised of all participants who received at least one dose of study treatment.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Bilirubin and Creatinine at Indicated Timepoints	Clinical chemistry parameters were assessed at Baseline (Day 1), Weeks 4, 12, 24, 36 and 48. Change from Baseline in bilirubin and creatinine are summarized. Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Albumin at Indicated Timepoints	Clinical chemistry parameters were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and Week 48. Change from Baseline in albumin is summarized. Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase at Indicated Time Points	Clinical chemistry parameters were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and Week 48. Change from Baseline in alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatine kinase is summarized. Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Creatinine Clearance at Indicated Time Points	Clinical chemistry parameters were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and Week 48. Change from Baseline in creatinine clearance is summarized. Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Lipase at Indicated Timepoints	Clinical chemistry parameters were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and Week 48. Change from Baseline in lipase is summarized. Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Total CHLS/HDL CHLS Ratio at Indicated Timepoints	Clinical chemistry parameters were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and Week 48. Change from Baseline in Total CHLS/HDL CHLS ratio is summarized. Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes at Indicated Time Points	Hematology parameters were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and Week 48. Change from Baseline in basophils, eosinophils, lymphocytes, monocytes is summarized. Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Erythrocytes at Indicated Time Points	Hematology parameters were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and Week 48. Change from Baseline in erythrocytes is summarized. Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Hematocrit Count at Indicated Time Points	Hematology parameters were assessed at Baseline (Day 1), Weeks 4, 12, 24, 36 and 48. Change from Baseline in hematocrit is summarized. Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Erythrocyte Mean Corpuscular Volume at Indicated Time Points	Hematology parameters were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and Week 48. Change from Baseline in erythrocyte mean corpuscular volume (EMCV) is summarized. Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Triglycerides at Week 48	Change from Baseline in mean triglycerides is summarized at Week 48. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean is the estimated mean change from Baseline in fasted triglycerides at Week 48 in each arm calculated from a model adjusted for the following covariates: treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age and triglycerides at Baseline. Participants on lipid lowering therapy at Baseline were excluded from analysis. Measurements collected after a participant initiates lipid lowering therapy were set to missing. Missing values were imputed using multiple imputation under a multivariate normal model adjusting for Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, fasted triglycerides and TC/HDL ratio at Baseline, Week 12 and Week 36.	Baseline (Day 1) and Week 48
Change From Baseline in TC/HDL Ratio at Week 48	Change from Baseline in mean total cholesterol (TC)/HDL ratio is summarized at Week 48. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean is the estimated mean change from Baseline in fasted TC/HDL at Week 48 in each arm calculated from a model adjusted for the following covariates: treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age and triglycerides/HDL at Baseline. Participants on lipid lowering therapy at Baseline were excluded from analysis. Measurements collected after a participant initiates lipid lowering therapy were set to missing. Missing values were imputed using multiple imputation under a multivariate normal model adjusting for Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, fasted triglycerides and TC/HDL ratio at Baseline, Week 12 and Week 36.	Baseline (Day 1) and Week 48
Change From Baseline in Urine Albumin Creatinine Ratio at Indicated Time Points	Change from Baseline in urine albumin creatinine ratio at Week 24 and Week 48 is summarized. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Week 24 and Week 48
Number of Participants With AEs by Maximum Toxicity-Randomized Phase	Number of participants with Grade 1-4 AEs by maximum toxicity were assessed from the start of study treatment and until end of the Randomization phase. AEs are categorized into following grades as per The Division of Aqcuired Immuno Deficiency Syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table)- Grade 1- mild, Grade 2- moderate; Grade 3- severe and Grade 4- potentially life-threatening. Higher the grade, more severe the symptoms.	Up to Week 48
Number of Participants With AEs by Maximum Toxicity-Continuation Phase	Number of participants with Grade 1-4 AEs were assessed in Continuation Phase. AEs are categorized into following grades as per The Division of Aqcuired Immuno Deficiency Syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table)- Grade 1- mild, Grade 2- moderate; Grade 3- severe and Grade 4- potentially life-threatening. Higher the grade, more severe the symptoms.	From Weeks 48 to 432
Number of Participants With Any Adverse Events (AEs), and Serious Adverse Events (SAEs)-Randomized Phase	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or other events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the outcome listed above, liver injury and impaired liver function and grade 4 laboratory abnormalities. Number of participants with any AEs, and SAEs have been presented.	Up to Week 48
Number of Participants With Any AEs, and SAEs in Continuation Phase	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or other events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the outcome listed above, liver injury and impaired liver function and grade 4 laboratory abnormalities. Number of participants with any AEs, and SAEs have been presented.	From Weeks 48 to 432
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities-Randomized Phase	Number of participants with Grade 1-4 emergent chemistry toxicities were assessed from the start of study treatment and end of Randomized Phase. Chemistry toxicities were categorized into following grades as per The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table)- Grade 1- mild, Grade 2- moderate; Grade 3- severe and Grade 4- potentially life-threatening. Higher the grade, more severe the symptoms. Data has been reported for clinical chemistry parameters including hyperglycaemia, hyperkalemia, hypernatremia, hypoglycaemia, hypokalemia, hyponatremia, alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, carbon dioxide, cholesterol, creatine kinase, creatinine, LDL cholesterol calculation, LDL cholesterol direct, lipase, phosphate, potassium, sodium, triglycerides and glucose.	Up to Week 48
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities-Continuation Phase	Number of participants with grades 1-4 emergent chemistry toxicities were assessed in Continuation Phase. Chemistry toxicities were categorized into following grades as per The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table)- Grade 1- mild, Grade 2- moderate; Grade 3- severe and Grade 4- potentially life-threatening. Higher the grade, more severe the symptoms. Data has been reported for clinical chemistry parameters including hyperglycaemia, hypernatremia, hypoglycaemia, hypokalemia, hyponatremia, alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, carbon dioxide, cholesterol, creatine kinase, creatinine, LDL cholesterol calculation, LDL cholesterol direct, lipase, phosphate, potassium, sodium, triglycerides and glucose.	From Weeks 48 to 432
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities-Randomized Phase	Number of participants with Grade 1-4 emergent hematology toxicities were assessed from the start of study treatment and end of Randomized Phase. Hematology toxicities were categorized into following grades as per The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table)- Grade 1- mild, Grade 2- moderate; Grade 3- severe and Grade 4- potentially life-threatening. Higher the grade, more severe the symptoms. Data has been reported for clinical chemistry parameters including hemoglobin, leukocytes, neutrophils and platelets.	Up to Week 48
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities-Continuation Phase	Number of participants with Grade 1-4 emergent hematology toxicities were assessed in Continuation Phase. Hematology toxicities were categorized into following grades as per The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table)- Grade 1- mild, Grade 2- moderate; Grade 3- severe and Grade 4- potentially life-threatening. Higher the grade, more severe the symptoms. Data has been reported for clinical chemistry parameters including hemoglobin, leukocytes, neutrophils and platelets.	From Weeks 48 to 432
Number of Participants Who Withdrew From Treatment Due to AEs-Randomized Phase	An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of an MP. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or is associated with liver injury and impaired liver function.	Up to Week 48
Number of Participants Who Withdrew From Treatment Due to AEs-Continuation Phase	An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of an MP. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or is associated with liver injury and impaired liver function.	From Weeks 48 to 432
Change From Baseline in Bone Specific Alkaline Phosphatase, Osteocalcin and Procollagen 1 N-terminal Propeptide at Indicated Timepoints	Bone markers were assessed at Baseline (Day 1), Weeks 24, 48. Change from Baseline in bone specific alkaline phosphatase (BSAP), osteocalcin and procollagen 1 N-terminal propeptide (PTP) is summarized. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Weeks 24 and 48
Change From Baseline in Type I Collagen C-telopeptides at Indicated Timepoints	Bone markers were assessed at Baseline (Day 1), Weeks 24, 48. Change from Baseline in Type I collagen C-telopeptides (T-1 CCT) is summarized. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Weeks 24 and 48
Change From Baseline in Vitamin D, Vitamin D2 and Vitamin D3 at Week 24 and Week 48	Bone markers were assessed at Baseline (Day 1), Weeks 24, 48. Change from Baseline in vitamin D, vitamin D2 and vitamin D3 is summarized. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1), Weeks 24 and 48
Bone Specific Alkaline Phosphatase, Osteocalcin, Procollagen 1 N-terminal Propeptide, Type 1 Collagen C-Telopeptide, Vitamin D Ratio of Week 48 Results Over Baseline	Bone markers were assessed at indicated timepoints. Bone specific alkaline phosphatase (BSAP), osteocalcin and procollagen 1 N-terminal propeptide (PTP), Type 1 Collagen C-Telopeptide, vitamin D ratio of Week 48 results over Baseline is calculated. Bone biomarkers were analyzed based on log transformed data. Estimates of adjusted mean and difference were calculated from an Analysis of covariance (ANCOVA) model adjusting for age, baseline viral load Baseline CD4+ cell count, Baseline biomarker level, body mass index category, smoking status and baseline Vitamin D use. Adjusted mean of log-transformed change from Baseline are transformed back to Week 48/Baseline ratio for each treatment group. Adjusted difference of log-transformed change from Baseline between treatment groups is transformed back to the ratio of Week 48/Baseline ratio in DTG/ABC/3TC FDC to ATV+RTV+TDF/FTC FDC.	Baseline (Day 1) and Week 48
Change From Baseline at Week 48 in SF-12 Total Score, MCS and PCS	The 12-Item Short Form Health Survey (SF-12) is 12 item abbreviated form of SF-36 survey. SF-12 questions make up 8 scales: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health. SF-12 is a self-reported outcome measure assessing psychological wellness and the impact of health on an individual's everyday life. SF-12 total score ranges from 20 to 60 and higher score indicate a higher level of functioning. SF-12 total score was calculated by a clinician scoring 12-question survey filled by participants. Transformed physical component summary score (PCS) and transformed mental component summary score (MCS) are derived using the sum of all 12 items and scored onto a 0-100 scale such that a higher score indicates a better health state and better functioning. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Change from Baseline was calculated as post-dose visit value minus Baseline value.	Baseline (Day 1) and Week 48
HIVTSQs Total Score at Indicated Timepoints	The HIV treatment satisfaction questionnaire (HIVTSQ) is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g. convenience, flexibility. The HIVTSQ items are summed up to produce a treatment satisfaction total score (0 to 60) and an individual satisfaction rating for each item (0 to 6) and two subscales: general satisfaction/clinical and lifestyle/ease subscales. The higher the score, the greater the improvement in treatment satisfaction as compared to the past few weeks. A smaller score represents a decline in treatment satisfaction compared to the past few weeks. Statistical analysis was performed based on Wilcoxon rank sum test.	Weeks 4, 12, 24 and 48
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 48 by Subgroups	Percentage of participants with plasma HIV-1 RNA <50 copies/mL at Week 48 by subgroups (age, race, country, Baseline plasma HIV-1 RNA [BPHR], Baseline CD4+ cell count [BCCC], Baseline Centers for Disease Control and Prevention [CDC] category and HIV-1 subtype) were assessed using the Snapshot algorithm (Missing, Switch or Discontinuation = Failure). Analysis was performed using a stratified analysis with CMH weights, adjusting for Baseline plasma HIV-1 RNA ( =<versus [vs]. >100,000 c/mL) and CD4+ cell count (=<350 cells/mm^3 or >350 cells/mm^3). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT population. Percentage values are rounded off.	Week 48
Number of Participants With Post-Baseline HIV-1 Disease Progression-Randomized Phase	Number of participants with post-Baseline HIV-1disease progression were assessed during study period. The CDC Classification System for HIV Infection is the medical classification system used by the United States Centers for Disease Control and Prevention (CDC) to classify HIV disease and infection. The clinical categories of HIV infection are defined as follows: Category A: Mildly symptomatic, Category B: Moderately symptomatic, Category C: Severely symptomatic. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Only those participants available at the specified time points were analyzed. Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT population.	Up to week 48
Number of Participants With Post-Baseline HIV-1 Disease Progression for DTG 50 mg/ABC 600 mg/3TC 300 mg QD (Randomized + Continuation Phase)	Number of participants with post-Baseline HIV-1disease progression were assessed during study period. The CDC Classification System for HIV Infection is the medical classification system used by the United States Centers for Disease Control and Prevention (CDC) to classify HIV disease and infection. The clinical categories of HIV infection are defined as follows: Category A: Mildly symptomatic, Category B: Moderately symptomatic, Category C: Severely symptomatic. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. Only those participants available at the specified time points were analyzed. Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT population.	Up to week 432
Number of Participants With Treatment Emergent Resistances for DTG 50 mg/ABC 600 mg/3TC 300 mg QD (Randomized + Continuation Phase)	Number of participants, who meet confirmed virologic withdrawal criteria, with treatment emergent genotypic resistance to integrase strand transfer inhibitor (INSTI), Non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), protease inhibitors (PI) will be summarized. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. On-treatment Genotypic Resistance Population comprised of all participants in the ITTE population with available On-treatment genotypic resistance data at the time confirmed virologic withdrawal criterion was met.	Up to week 432
Number of Participants With Treatment Emergent Resistances for ATV 300 mg+RTV 100 mg+TDF 300 mg/FTC 200mg QD (Randomized Phase)	Number of participants, who meet confirmed virologic withdrawal criteria, with treatment emergent genotypic resistance to integrase strand transfer inhibitor (INSTI), Non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), protease inhibitors (PI) will be summarized. The Baseline value was defined as the latest pre-dose assessment (Day 1) value. On-treatment Genotypic Resistance Population comprised of all participants in the ITTE population with available On-treatment genotypic resistance data at the time confirmed virologic withdrawal criterion was met.	Up to week 48

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, ViiV Healthcare

Publications and helpful links

General Publications

• Orrell C, Hagins DP, Belonosova E, Porteiro N, Walmsley S, Falco V, Man CY, Aylott A, Buchanan AM, Wynne B, Vavro C, Aboud M, Smith KY; ARIA study team. Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study. Lancet HIV. 2017 Dec;4(12):e536-e546. doi: 10.1016/S2352-3018(17)30095-4. Epub 2017 Jul 17. Erratum In: Lancet HIV. 2017 Dec;4(12 ):e535.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2013
• Primary Completion (Actual): September 22, 2015
• Study Completion (Actual): August 18, 2022

Study Registration Dates

• First Submitted: July 25, 2013
• First Submitted That Met QC Criteria: July 26, 2013
• First Posted (Estimated): July 29, 2013

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: women; HIV infection; integrase inhibitor; ritonavir; once daily; dolutegravir/abacavir/lamivudine fixed dose combination; atazanavir; antiretroviral therapy naïve; tenofovir/emtricitabine
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Disease Attributes; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Ritonavir; Lamivudine; Atazanavir Sulfate; Dolutegravir; Abacavir
• Other Study ID Numbers: 117172; 2012-005823-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on ViiV's data sharing criteria can be found at: https://viivhealthcare.com/about-viiv/corporate-ethics-compliance/commitment-to-data-transparency/
• IPD Sharing Time Frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No