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)

• ClinicalTrials.gov Identifier: NCT01910402
• Recruitment Status: Completed
• First Posted: July 29, 2013
• Results First Posted: October 31, 2016
• Last Update Posted: September 29, 2022
• Sponsor: ViiV Healthcare
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): ViiV Healthcare

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
Infection, Human Immunodeficiency Virus; HIV Infections	Drug: Dolutegravir/abacavir/lamivudine FDC; Drug: Atazanavir; Drug: Ritonavir; Drug: Tenofovir/emtricitabine FDC	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 499 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 22, 2013
• Actual Primary Completion Date: September 22, 2015
• Actual Study Completion Date: August 18, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 48 [ Time Frame: 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 millimetre cube (cells/mm^3) or >350 cells/mm^3). Intent-to-Treat Exposed (ITT-E) Population comprised of all randomised participants who received at least one dose of study medication.

Secondary Outcome Measures :

1. Percentage of Participants With Plasma HIV-1 RNA <50 and <400 c/mL Over Time [ Time Frame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48 ]
   Percentage of participants with plasma HIV-1 RNA <50 and <400 c/mL were assessed at Baseline, Week 4, 12, 24 , 36 and Week 48 using the Snapshot algorithm (Missing, Switch or Discontinuation = Failure). The Baseline value was defined as the latest pre-dose assessment (Day 1) value.
2. Change From Baseline in Plasma HIV-1 RNA at Indicated Time Points [ Time Frame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48 ]
   Change from the Baseline in plasma HIV-1 RNA were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and 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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
3. Change From Baseline in CD4+ Cell Count at Indicated Timepoints [ Time Frame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48 ]
   Change from Baseline in cluster of differentiation 4(CD4+) cell count were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and 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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
4. Change From Baseline in Carbon Dioxide, Electrolytes, Lipids, Glucose, Urea at Indicated Time Points [ Time Frame: Baseline, Week 4, 12, 24, 36, 48 ]
   Clinical chemistry parameters were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and Week 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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
5. Change From Baseline in Bilirubin and Creatinine at Indicated Timepoints. [ Time Frame: Baseline, Week 4, 12, 24, 36, 48 ]
   Clinical chemistry parameters were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and Week 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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
6. Change From Baseline in Albumin at Indicated Timepoints. [ Time Frame: Baseline, Week 4, 12, 24, 36, 48 ]
   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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
7. Change From Baseline in Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase at Indicated Time Points [ Time Frame: Baseline, Week 4, 12, 24, 36, 48 ]
   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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
8. Change From Baseline in Creatinine Clearance at Indicated Time Points [ Time Frame: Baseline, Week 4, 12, 24, 36, 48 ]
   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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
9. Change From Baseline in Lipase at Indicated Timepoints. [ Time Frame: Baseline, Week 4, 12, 24, 36, 48 ]
   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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
10. Change From Baseline in Total CHLS/HDL CHLS Ratio at Indicated Timepoints. [ Time Frame: Baseline, Week 4, 12, 24, 36, 48 ]
    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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
11. Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes at Indicated Time Points [ Time Frame: Baseline, Week 4, 12, 24, 36, 48 ]
    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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
12. Change From Baseline in Erythrocytes at Indicated Time Points. [ Time Frame: Baseline, Week 4, 12, 24, 36, 48 ]
    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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
13. Change From Baseline in Hematocrit Count at Indicated Time Points. [ Time Frame: Baseline, Week 4, 12, 24, 36, 48 ]
    Hematology parameters were assessed at Baseline (Day 1), Week 4, 12, 24, 36 and Week 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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
14. Change From Baseline in Erythrocyte Mean Corpuscular Volume at Indicated Time Points. [ Time Frame: Baseline, Week 4, 12, 24, 36, 48 ]
    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. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
15. Change From Baseline in Triglycerides at Week 48 [ Time Frame: Baseline and 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. Subjects on lipid lowering therapy at baseline were excluded from analysis. Measurements collected after a subject 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.
16. Change From Baseline in TC/HDL Ratio at Week 48 [ Time Frame: Baseline and 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. Subjects on lipid lowering therapy at baseline were excluded from analysis. Measurements collected after a subject 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.
17. Change From Baseline in Urine Albumin Creatinine Ratio at Indicated Time Points [ Time Frame: Baseline, Week 24, Week 48 ]
    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. Only those participants available at the specified time points were analyzed.
18. Summary of AEs by Maximum Toxicity as Per DAIDS AE Grading Table. [ Time Frame: Average of 354 days for DTG/ABC/3TC, and average of 336 days for ATV+RTV+TDF/FTC ]
    Number of participants with Grade 1-4 AEs were assessed from the start of study treatment and until end of the Randimization 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 Grade 4- potentially life-threatening.
19. Number of Participants With Any Adverse Events (AEs), and Serious Adverse Events (SAEs) [ Time Frame: From start of IP through the Study Phase (Average of 354 days for DTG/ABC/3TC, and average of 336 days for ATV+RTV+TDF/FTC) ]
    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. A serious adverse event (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.
20. Summary of Maximum Post-Baseline Emergent Chemistry Toxicities [ Time Frame: Average of 354 days for DTG/ABC/3TC, and average of 336 days for ATV+RTV+TDF/FTC ]
    Number of participants with Grade 1-4 emergent chemistry toxicities were assessed from the start of study treatment and until the follow up contact. 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 Grade 4- potentially life-threatening.
21. Summary of Maximum Post-Baseline Emergent Hematology Toxicities [ Time Frame: Average of 354 days for DTG/ABC/3TC, and average of 336 days for ATV+RTV+TDF/FTC ]
    Number of participants with Grade 1-4 emergent hematology toxicities were assessed from the start of study treatment and until the follow up contact. 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 Grade 4- potentially life-threatening.
22. Number of Participants Who Withdrew From Treatment Due to AEs [ Time Frame: average of 354 days for DTG/ABC/3TC, and average of 336 days for ATV+RTV+TDF/FTC ]
    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.
23. Change From Baseline in Bone Specific Alkaline Phosphatase, Osteocalcin and Procollagen 1 N-terminal Propeptide at Indicated Timepoints [ Time Frame: Baseline, Week 24, 48 ]
    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. Only those participants available at the specified time points (represented by n=X, X in the category titles) were analyzed.
24. Change From Baseline in Type I Collagen C-telopeptides at Indicated Timepoints [ Time Frame: Baseline, Week 24, 48 ]
    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. Only those participants available at the specified time points (represented by n=X, X in the category titles) were analyzed.
25. Change From Baseline in Vitamin D, Vitamin D2 and Vitamin D3 at Week 24 and Week 48 [ Time Frame: Baseline, Weeks 24, 48 ]
    Bone markers were assessed at Baseline (Day 1), Weeks 24, 48. Change from Baseline in vitamin D and vitamin D2 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. Only those participants available at the specified time points (represented by n=X, X in the category titles) were analyzed.
26. Bone Specific Alkaline Phosphatase, Osteocalcin, Procollagen 1 N-terminal Propeptide, Type 1 Collagen C-Telopeptide, Vitamin D Ratio of Week 48 Results Over Baseline [ Time Frame: Baseline, Weeks 24, 48 ]
    Bone markers were assessed at Baseline (Day 1), Weeks 24, 48. 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 analysed based on log transformed data. Only those participants available at the specified time points (represented by n=X, X in the category titles) were analyzed. Estimates of adjusted mean and difference were calculated from an 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.
27. Change From Baseline at Week 48 in SF-12 Total Score, MCS and PCS [ Time Frame: Baseline and Week 48 ]
    The SF-12 is the 12 item abbreviated form of SF-36 survey. It provides information about how participants feel, and how well they have been able to perform their usual activities. SF-12 questions make up 8 scales: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health . 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. Only those participants available at the specified time points (represented by n=X, X in the category titles) were analyzed.
28. Assessment of HIVTSQs Total Score at Indicated Timepoints. [ Time Frame: Week 4, 12, 24, 48 ]
    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 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. Only those participants available at the specified time points (represented by n=X, X in the category titles) were analyzed.
29. Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 48 by Subgroups [ Time Frame: Week 48 ]
    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 ( =<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.
30. Number of Participants With Post-Baseline HIV-1 Disease Progression [ Time Frame: Up to week 48 ]
    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.
31. Number of Participants With Treatment Emergent Resistances [ Time Frame: Up to week 48 ]
    Number of participants, who meet confirmed virologic withdrawal criteria, with treatment emergent genotypic resistance to INI, NNRTI, NRTI, 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 ITT-E population with available On-treatment genotypic resistance data at the time confirmed virologic withdrawal criterion was met.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

GSK Investigational Site

Phoenix, Arizona, United States, 85015

United States, California

GSK Investigational Site

Bakersfield, California, United States, 93301

GSK Investigational Site

Beverly Hills, California, United States, 90211

United States, District of Columbia

GSK Investigational Site

Washington, District of Columbia, United States, 20007

United States, Florida

GSK Investigational Site

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

United States, Georgia

GSK Investigational Site

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

United States, Indiana

GSK Investigational Site

Indianapolis, Indiana, United States, 46202

United States, Massachusetts

GSK Investigational Site

Springfield, Massachusetts, United States, 01199

United States, Michigan

GSK Investigational Site

Detroit, Michigan, United States, 48202

United States, Missouri

GSK Investigational Site

Kansas City, Missouri, United States, 64111

GSK Investigational Site

Saint Louis, Missouri, United States, 63110

United States, Nebraska

GSK Investigational Site

Omaha, Nebraska, United States, 68198

United States, Nevada

GSK Investigational Site

Las Vegas, Nevada, United States, 89106

United States, New Jersey

GSK Investigational Site

Neptune, New Jersey, United States, 7754

GSK Investigational Site

Newark, New Jersey, United States, 07103

United States, New York

GSK Investigational Site

Buffalo, New York, United States, 14215

GSK Investigational Site

Valhalla, New York, United States, 10595

United States, North Carolina

GSK Investigational Site

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

United States, Pennsylvania

GSK Investigational Site

Allentown, Pennsylvania, United States, 18102

GSK Investigational Site

Philadelphia, Pennsylvania, United States, 19104

GSK Investigational Site

Philadelphia, Pennsylvania, United States, 19107

GSK Investigational Site

Philadelphia, Pennsylvania, United States, 19140

United States, Texas

GSK Investigational Site

Bellaire, Texas, United States, 77401

GSK Investigational Site

Dallas, Texas, United States, 75235

GSK Investigational Site

Dallas, Texas, United States, 75246

GSK Investigational Site

El Paso, Texas, United States, 79905

GSK Investigational Site

Fort Worth, Texas, United States, 76104

United States, Virginia

GSK Investigational Site

Lynchburg, Virginia, United States, 24501

Argentina

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1405CKC

GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, Argentina, C1202ABB

GSK Investigational Site

Buenos Aires, Argentina, 1141

Canada, British Columbia

GSK Investigational Site

Vancouver, British Columbia, Canada, V6Z 1Y6

Canada, Ontario

GSK Investigational Site

Ottawa, Ontario, Canada, K1H 8L6

GSK Investigational Site

Toronto, Ontario, Canada, M4N 3M5

GSK Investigational Site

Toronto, Ontario, Canada, M5G 2N2

Canada, Quebec

GSK Investigational Site

Montreal, Quebec, Canada, H2X 2P4

France

GSK Investigational Site

Bobigny, France, 93009

GSK Investigational Site

Nantes, France, 44093

GSK Investigational Site

Paris Cedex 10, France, 75475

Italy

GSK Investigational Site

Genova, Liguria, Italy, 16128

GSK Investigational Site

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

Torino, Piemonte, Italy, 10149

Mexico

GSK Investigational Site

Guadalajara, Jalisco, Mexico, 44280

GSK Investigational Site

Mexico, Mexico, 14000

Portugal

GSK Investigational Site

Amadora, Portugal, 2720-276

GSK Investigational Site

Lisboa, Portugal, 1150

GSK Investigational Site

Porto, Portugal, 4200-319

Puerto Rico

GSK Investigational Site

Ponce, Puerto Rico, 00717

GSK Investigational Site

San Juan, Puerto Rico, 00909

Russian Federation

GSK Investigational Site

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, 190103

GSK Investigational Site

St. Petersburg, Russian Federation, 196645

GSK Investigational Site

Toliyatti, Russian Federation, 445846

South Africa

GSK Investigational Site

Observatory, Cape Town, Western Province, South Africa, 7925

GSK Investigational Site

Mamelodi East, South Africa, 122

Spain

GSK Investigational Site

(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, 28034

GSK Investigational Site

Madrid, Spain, 28046

GSK Investigational Site

Malaga, Spain, 29010

GSK Investigational Site

Murcia, Spain, 30003

GSK Investigational Site

Sevilla, Spain, 41013

Thailand

GSK Investigational Site

Bangkok, Thailand, 10330

GSK Investigational Site

Nonthaburi, Thailand, 11000

United Kingdom

GSK Investigational Site

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

Sponsors and Collaborators

ViiV Healthcare

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; ViiV Healthcare

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: ViiV Healthcare
• ClinicalTrials.gov Identifier: NCT01910402
• Other Study ID Numbers: 117172; 2012-005823-34 ( EudraCT Number )
• First Posted: July 29, 2013
• Results First Posted: October 31, 2016
• Last Update Posted: September 29, 2022
• Last Verified: September 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ViiV Healthcare:

antiretroviral therapy naïve; women; once daily; HIV infection; atazanavir; tenofovir/emtricitabine; dolutegravir/abacavir/lamivudine fixed dose combination; integrase inhibitor; ritonavir

Additional relevant MeSH terms:

Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Disease Attributes; Pathologic Processes; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immune System Diseases; Slow Virus Diseases; Ritonavir; Atazanavir Sulfate; Tenofovir; Lamivudine; Emtricitabine; Dolutegravir; Abacavir; HIV Protease Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action