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)

NCT01910402 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 1171722012-005823-34
• Study Type: interventional
• Target: 499
• Locations: 13 countries
• Sites: 90

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)

Conditions

Infection, Human Immunodeficiency Virus; HIV Infections

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (45)

• Percentage of Participants With Plasma HIV-1 RNA <50 and <400 c/mL Over Time-Randomized Phase

  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

  Week 96 and Week 432

• Change From Baseline in Plasma HIV-1 RNA at Indicated Time Points-Randomized Phase

  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

  Baseline (Day 1), Week 96 and Week 432

• Absolute Values in Plasma HIV-1 RNA at Indicated Time Points-Randomized Phase

  Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48

Study Arms (2)

DTG/ABC/3TC FDC

EXPERIMENTAL

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

ATV +RTV +TDF/FTC FDC

ACTIVE COMPARATOR

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; Drug: Ritonavir; Drug: Tenofovir/emtricitabine FDC

Interventions

Dolutegravir/abacavir/lamivudine FDC DRUG

Dolutegravir/abacavir/lamivudine FDC tablets, 50 mg/600 mg/300 mg

DTG/ABC/3TC FDC

Atazanavir DRUG

Atazanavir capsule 300 mg

ATV +RTV +TDF/FTC FDC

Ritonavir DRUG

Ritonavir tablet 100 mg

ATV +RTV +TDF/FTC FDC

Tenofovir/emtricitabine FDC DRUG

Tenofovir/emtricitabine FDC tablet 300 mg/200 mg of FTC

ATV +RTV +TDF/FTC FDC

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator

Study Sites (90)

GSK Investigational Site

Phoenix, Arizona, 85015, United States

Location

GSK Investigational Site

Bakersfield, California, 93301, United States

Location

GSK Investigational Site

Beverly Hills, California, 90211, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

GSK Investigational Site

Ft. Pierce, Florida, 34982, United States

Location

GSK Investigational Site

Miami, Florida, 33133, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

Tampa, Florida, 33602, United States

Location

GSK Investigational Site

West Palm Beach, Florida, 33401, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30309, United States

Location

GSK Investigational Site

Augusta, Georgia, 30912-3130, United States

Location

GSK Investigational Site

Decatur, Georgia, 30033, United States

Location

GSK Investigational Site

Savannah, Georgia, 31401, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46202, United States

Location

GSK Investigational Site

Springfield, Massachusetts, 01199, United States

Location

GSK Investigational Site

Detroit, Michigan, 48202, United States

Location

GSK Investigational Site

Kansas City, Missouri, 64111, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68198, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89106, United States

Location

GSK Investigational Site

Neptune City, New Jersey, 7754, United States

Location

GSK Investigational Site

Newark, New Jersey, 07103, United States

Location

GSK Investigational Site

Buffalo, New York, 14215, United States

Location

GSK Investigational Site

Valhalla, New York, 10595, United States

Location

GSK Investigational Site

Chapel Hill, North Carolina, 27514, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28207, United States

Location

GSK Investigational Site

Greensboro, North Carolina, 27401-1209, United States

Location

GSK Investigational Site

Allentown, Pennsylvania, 18102, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19107, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19140, United States

Location

GSK Investigational Site

Bellaire, Texas, 77401, United States

Location

GSK Investigational Site

Dallas, Texas, 75235, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

El Paso, Texas, 79905, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Lynchburg, Virginia, 24501, United States

Location

GSK Investigational Site

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

Location

GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, C1202ABB, Argentina

Location

GSK Investigational Site

Buenos Aires, 1141, Argentina

Location

GSK Investigational Site

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

GSK Investigational Site

Ottawa, Ontario, K1H 8L6, Canada

Location

GSK Investigational Site

Toronto, Ontario, M4N 3M5, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2N2, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2X 2P4, Canada

Location

GSK Investigational Site

Bobigny, 93009, France

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Paris, 75475, France

Location

GSK Investigational Site

Genoa, Liguria, 16128, Italy

Location

GSK Investigational Site

Bergamo, Lombardy, 24127, Italy

Location

GSK Investigational Site

Brescia, Lombardy, 25123, Italy

Location

GSK Investigational Site

Busto Arsizio (VA), Lombardy, 21052, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20127, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20157, Italy

Location

GSK Investigational Site

Turin, Piedmont, 10149, Italy

Location

GSK Investigational Site

Guadalajara, Jalisco, 44280, Mexico

Location

GSK Investigational Site

México, 14000, Mexico

Location

GSK Investigational Site

Amadora, 2720-276, Portugal

Location

GSK Investigational Site

Lisbon, 1150, Portugal

Location

GSK Investigational Site

Porto, 4200-319, Portugal

Location

GSK Investigational Site

Ponce, 00717, Puerto Rico

Location

GSK Investigational Site

Rio Piedras, 00936, Puerto Rico

Location

GSK Investigational Site

San Juan, 00909, Puerto Rico

Location

GSK Investigational Site

Moscow, 115035, Russia

Location

GSK Investigational Site

Oryol, 302040, Russia

Location

GSK Investigational Site

Saint Petersburg, 190103, Russia

Location

GSK Investigational Site

Saint Petersburg, 196645, Russia

Location

GSK Investigational Site

Smolensk, 214006, Russia

Location

GSK Investigational Site

Toliyatti, 445846, Russia

Location

GSK Investigational Site

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

Location

GSK Investigational Site

Mamelodi East, 122, South Africa

Location

GSK Investigational Site

(Móstoles) Madrid, 28935, Spain

Location

GSK Investigational Site

Alicante, 03010, Spain

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Barcelona, 08907, Spain

Location

GSK Investigational Site

Granada, 18012, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Murcia, 30003, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

GSK Investigational Site

Bangkok, 10330, Thailand

Location

GSK Investigational Site

Nonthaburi, 11000, Thailand

Location

GSK Investigational Site

Birmingham, B9 5SS, United Kingdom

Location

GSK Investigational Site

London, E1 1BB, United Kingdom

Location

GSK Investigational Site

London, NW3 2QG, United Kingdom

Location

GSK Investigational Site

London, W2 1NY, United Kingdom

Location

GSK Investigational Site

Sheffield, S10 2JF, United Kingdom

Location

GSK Investigational Site

Tooting, London, SW17 0QT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 28729158 DERIVED

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

dolutegravir; Atazanavir Sulfate; Ritonavir; Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Organophosphonates; Organophosphorus Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2013
• First Posted: July 29, 2013
• Study Start: August 22, 2013
• Primary Completion: September 22, 2015
• Study Completion: August 18, 2022
• Last Updated: February 20, 2024
• Results First Posted: October 31, 2016

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

PT (3); ME (2); FR (3); PR (3); RU (6); CA (5); ZA (2); ES (11); AR (3); IT (7); TH (2); US (37); GB (6)