Induction/Simplification With Atazanavir + Ritonavir + Abacavir/Lamivudine Fixed-Dose Combination In HIV-1 Infection

NCT00440947 | Completed Phase 3 Results

• 1 other identifier: EPZ108859
• Study Type: interventional
• Target: 515
• Locations: 3 countries
• Sites: 72

Brief Summary

This study was designed to test the efficacy, safety, tolerability and durability of the antiviral response between atazanavir (ATV) + ritonavir (/r) + abacavir/lamivudine(ABC/3TC) Fixed dose combination (FDC) each administered once daily (QD) for 36 weeks followed by randomization to either a simplification regimen of ATV or continuation of ATV +/r for an additional 48 weeks, each in combination with ABC/3TC in antiretroviral (ART)-naive, HIV-1 infected, HLA-B\*5701 negative subjects. All subjects who complete the 84-week study will be eligible to enter the treatment extension phase and continue for an additional 60 weeks. The purpose of this extension is to obtain longer term treatment data in subjects who have completed the 84-week study.

Conditions

Infection, Human Immunodeficiency Virus I; HIV Infection

Keywords

NORVIR; ARIES; EPZICOM; REYATAZ; HIV; simplification; Antiretroviral-naive

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 Copies (c) /Milliliter (ml) at the Week 84 Visit

  The percentage of PAR with HIV-1 RNA virus \<50 c/ml determined from a blood sample drawn at Week 84 was tabulated by treatment arm with stratification by baseline HIV-1 RNA (\<100,000 c/ml and \>=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed viral load \<50 c/ml who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA \<50 c/ml, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 50 c/ml, or had an unconfirmed HIV RNA of at least 50 c/ml at last visit.

  Week 84

Secondary Outcomes (25)

• Mean Age at Baseline of Participants Randomized to Treatment for the 48-Week Randomized Phase

  Baseline of Randomized Phase

• Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 36 Visit

  Week 36

• Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 84 Visit

  Week 84

• Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 144 Visit

  Week 144

• Percentage of Participants Who Achieved Plasma HIV-1 RNA <400 c/ml at the Week 36 Visit

  Week 36

Study Arms (2)

Simplification

OTHER

Atazanavir (ATV) 400 mg QD + abacavir (ABC) 600 mg/lamivudine (3TC) 300 mg fixed dose combination (FDC) QD for 48 weeks followed by optional treatment extension for 60 weeks on the same regimen.

Drug: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV)

Continuation

OTHER

Atazanavir (ATV) 300 mg QD + ritonavir (/r) 100 mg QD + abacavir (ABC) 600mg/lamivuidine (3TC )300 mg FDC QD for 48 weeks followed by optional treatment extension for 60 weeks on the same regimen.

Drug: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) + ritonavir (/r)

Interventions

Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) + ritonavir (/r) DRUG

Abacavir (ABC)/lamivudine (3TC) FDC + atazanavir (ATV)+ ritoanvir (/r) for 36weeks followed by ABC/3TC + ATV + /r for 48wks followed by optional treatment extension for 60 weeks on the same regimen

Continuation

Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) DRUG

Abacavir (ABC)/lamivudine (3TC) FDC + atazanavir (ATV) + ritonavir (/r) for 36 weeks followed by ABC/3TC + ATV for 48wks followed by optional treatment extension for 60 weeks on the same regimen

Simplification

Eligibility Criteria

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

You may qualify if:

• Subject is ≥ 18 years of age and has documented evidence of HIV-1 infection. (A female is eligible to enter and participate in this study if she is of: non child-bearing potential, child bearing potential with a negative pregnancy test and agrees to approved contraception methods, or agreement for complete abstinence.)
• Subject is antiretroviral-naïve (defined as having ≤14 days of prior therapy with any NRTI and no prior therapy with either a PI or NNRTI).
• Subject has plasma HIV-1 RNA ≥ 1,000 copies/mL by Roche COBAS AMPLICOR™ (Version 1.5) method at screening (if no other documentation of HIV infection is available, a positive result here may serve as documentation of HIV infection for this study).
• Subject is willing and able to understand and provide written informed consent prior to participation in this study.

You may not qualify if:

• Subject is HLA-B\*5701 positive.
• Subject testing positive for Hepatitis B or both Hepatitis B and Hepatitis C at screening (+ HbsAg)
• Genotyping results performed at the screening indicate that the subject has any of the following mutations at the reverse transcriptase (RT) enzyme: K65R, L74V, or Y115F, or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, or ≥ 3 of the following protease mutations associated with atazanavir resistance: D30, V32, M36, M46, I47, G48, I50, I54, A71, G73, V77, V82, I84, N88, and L90.
• Women who are pregnant or breastfeeding.
• Subject has an active or acute CDC Clinical Category C event at screening. Treatment for the acute event must have been completed at least 30 days prior to screening.
• Subject is, in the opinion of the investigator, unable to complete the 84-week dosing period and protocol evaluations and assessments.
• Subject has ongoing clinically relevant pancreatitis or clinically relevant hepatitis at screening.
• Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment.
• Subject suffers from a serious medical condition, such as diabetes, congestive heart failure, cardiomyopathy or other cardiac dysfunction (including known, clinically significant cardiac conduction system disease, severe first degree atrioventricular block \[PR interval \> 0.26 seconds\], second or third-degree atrioventricular block), which in the opinion of the investigator would compromise the safety of the subject.
• Subject has pre-existing mental, physical, or substance abuse disorder, which in the opinion of the investigator would interfere with the subject's ability to comply with the dosing schedule and protocol evaluations and assessments.
• Subject has a history of inflammatory bowel disease or malignancy, intestinal ischemia, malabsorption, or other gastrointestinal dysfunction, which may interfere with drug absorption or render the subject unable to take oral medication.
• Subject requires treatment with foscarnet, hydroxyurea or other agents with documented activity against HIV-1 in vitro within 28 days of study administration.
• Subject requires treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, vaccines, or interferons) within 28 days prior to screening, or subject had received an HIV-1 immunotherapeutic vaccine within 90 days prior to screening. Subjects using inhaled corticosteroids are eligible for enrollment.
• Creatinine clearance \<50 mL/min via the Cockroft-Gault method \[Cockroft, 1976\].
• Active alcohol or substance use sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis.

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator

Study Sites (72)

GSK Investigational Site

Phoenix, Arizona, 85012, United States

Location

GSK Investigational Site

Long Beach, California, 90813, United States

Location

GSK Investigational Site

Los Angeles, California, 90022, United States

Location

GSK Investigational Site

Los Angeles, California, 90033, United States

Location

GSK Investigational Site

Newport Beach, California, 92663, United States

Location

GSK Investigational Site

Oakland, California, 94609, United States

Location

GSK Investigational Site

Denver, Colorado, 80220, United States

Location

GSK Investigational Site

Glastonbury, Connecticut, 06033, United States

Location

GSK Investigational Site

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

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20009, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20036, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20037, United States

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33306, United States

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33308, United States

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33316, United States

Location

GSK Investigational Site

Ft. Pierce, Florida, 34982, United States

Location

GSK Investigational Site

Miami, Florida, 33136, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

Plantation, Florida, 33317, United States

Location

GSK Investigational Site

Sarasota, Florida, 34243, United States

Location

GSK Investigational Site

Tampa, Florida, 33602, United States

Location

GSK Investigational Site

Tampa, Florida, 33607, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30308, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30309, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30339, United States

Location

GSK Investigational Site

Augusta, Georgia, 30912, United States

Location

GSK Investigational Site

Decatur, Georgia, 30033, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Chicago, Illinois, 60657, United States

Location

GSK Investigational Site

Maywood, Illinois, 60153, United States

Location

GSK Investigational Site

Lexington, Kentucky, 40536, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21201, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02115, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02215, United States

Location

GSK Investigational Site

Detroit, Michigan, 48202, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55404, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55415, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

Hillsborough, New Jersey, 08844, United States

Location

GSK Investigational Site

Newark, New Jersey, 07102, United States

Location

GSK Investigational Site

Somers Point, New Jersey, 08244, United States

Location

GSK Investigational Site

New York, New York, 10011, United States

Location

GSK Investigational Site

Valhalla, New York, 10595, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28209, United States

Location

GSK Investigational Site

Greenville, North Carolina, 27834, United States

Location

GSK Investigational Site

Akron, Ohio, 44304, United States

Location

GSK Investigational Site

Toledo, Ohio, 43614, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19107, United States

Location

GSK Investigational Site

Providence, Rhode Island, 2906, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Dallas, Texas, 75204, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

El Paso, Texas, 79925, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Galveston, Texas, 77555, United States

Location

GSK Investigational Site

Houston, Texas, 77004, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Houston, Texas, 77057, United States

Location

GSK Investigational Site

Longview, Texas, 75605, United States

Location

GSK Investigational Site

Annandale, Virginia, 22003, United States

Location

GSK Investigational Site

Norfolk, Virginia, 23507, United States

Location

GSK Investigational Site

Toronto, Ontario, M4N 3M5, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5B 1L6, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2N2, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2L 4P9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2L 5B1, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2X 2P4, Canada

Location

GSK Investigational Site

Ponce, 00717, Puerto Rico

Location

GSK Investigational Site

Ponce, 00731, Puerto Rico

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GSK Investigational Site

San Juan, 00909-1711, Puerto Rico

Location

GSK Investigational Site

San Juan, 00910, Puerto Rico

Location

Related Publications (11)

• L Ross, E Dejesus, M Potter, A LaMarca, D Murphy, I Melendez-Rivera, D Ward, P Wannamaker, J Uy, L Patel, H Amrine-Madsen, J Horton. Epidemiological and Genotypic Clustering of HIV infection within North America During 2007 International HIV & Hepatitis Drug Resistance Workshop & Curative Strategies, 8-12 June 2010, Dubrovnik, Croatia, Poster 150.

  BACKGROUND

• Young B, Squires K, Patel P, Dejesus E, Bellos N, Berger D, Sutherland-Phillips DH, Liao Q, Shaefer M, Wannamaker P. First large, multicenter, open-label study utilizing HLA-B*5701 screening for abacavir hypersensitivity in North America. AIDS. 2008 Aug 20;22(13):1673-5. doi: 10.1097/QAD.0b013e32830719aa.

  PMID: 18670229 BACKGROUND

• • L Ross, K Squires, B Young, E DeJesus, N Bellos, D Murphy, A Rachlis, H Zhao, L Patel, L Ross, P Wannamaker, M Shaefer. Genotypic Screening Impact in ARIES [Atazanavir (ATV) + Ritonavir (/r) + Abacavir/Lamivudine (ABC/3TC) for 36 Weeks Followed By Randomization to ATV +ABC/3TC or ATV/r + ABC/3TC for 48 Wks in HIV-infected, ART Naïve Patients] :Low Rates of Virologic Failure. The 19th Annual Canadian Conference on HIV/AIDS Research, 13-16 May 2010, Saskatoon, Canada. Poster P-169.

  BACKGROUND

• K Squires, E DeJesus, N Bellos, D Ward, D Murphy, H Zhao, L Patel, L Ross, P Wannamaker, M Shaefer. Sustained Virologic Efficacy of Atazanavir (ATV) Versus Atazanavir/Ritonavir (ATV/r), each in Combination with Abacavir/Lamivudine (ABC/3TC) over 120 Weeks: the ARIES Trial. 48th ICAAC; September 12-15, 2010, Boston, MA. Poster H-204.

  BACKGROUND

• K Squires, B Young, E DeJesus, N Bellos, D Murphy, D Sutherland-Phillips, H Zhao, L Patel, L Ross, P Wannamaker, M Shaefer. Atazanavir/Ritonavir (ATV/r) + Abacavir/Lamivudine (ABC/3TC) in Antiretroviral (ART)-Naive HIV-1 Infected HLA-B*5701 Negative Subjects Demonstrates Efficacy and Safety: the ARIES Trial. 48th ICAAC; October 25-28, 2008, Washington, DC. Poster H-1250a.

  BACKGROUND

• K Squires, B Young, E DeJesus, N Bellos, D Murphy, D Sutherland-Phillips, H Zhao, L Patel, L Ross, P Wannamaker, M Shaefer. Similar Efficacy and Tolerability of Atazanavir (ATV) Compared to ATV/Ritonavir (RTV, r), Each in Combination with Abacavir/Lamivudine (ABC/3TC), after Initial Suppression with ABC/3TC + ATV/r in HIV-1 Infected Patients: 84 Week Results of the ARIES Trial. 5th IAS Conference; Cape Town, South Africa. Abstract WELBB103

  BACKGROUND

• Squires KE, Young B, DeJesus E, Bellos N, Murphy D, Sutherland-Phillips DH, Zhao HH, Patel LG, Ross LL, Wannamaker PG, Shaefer MS; ARIES Study Team. Safety and efficacy of a 36-week induction regimen of abacavir/lamivudine and ritonavir-boosted atazanavir in HIV-infected patients. HIV Clin Trials. 2010 Mar-Apr;11(2):69-79. doi: 10.1310/hct1102-69.

  PMID: 20542844 BACKGROUND

• Squires KE, Young B, Dejesus E, Bellos N, Murphy D, Zhao HH, Patel LG, Ross LL, Wannamaker PG, Shaefer MS; ARIES study team. Similar efficacy and tolerability of atazanavir compared with atazanavir/ritonavir, each with abacavir/lamivudine after initial suppression with abacavir/lamivudine plus ritonavir-boosted atazanavir in HIV-infected patients. AIDS. 2010 Aug 24;24(13):2019-27. doi: 10.1097/QAD.0b013e32833bee1b.

  PMID: 20613461 BACKGROUND

• Ross LL, Horton J, Hasan S, Brown JR, Murphy D, DeJesus E, Potter M, LaMarca A, Melendez-Rivera I, Ward D, Uy J, Shaefer MS. HIV-1 transmission patterns in antiretroviral therapy-naive, HIV-infected North Americans based on phylogenetic analysis by population level and ultra-deep DNA sequencing. PLoS One. 2014 Feb 26;9(2):e89611. doi: 10.1371/journal.pone.0089611. eCollection 2014.

  PMID: 24586911 DERIVED

• Squires KE, Young B, DeJesus E, Bellos N, Murphy D, Ward D, Zhao HH, Ross LL, Shaefer MS; ARIES Study Team. ARIES 144 week results: durable virologic suppression in HIV-infected patients simplified to unboosted atazanavir/abacavir/lamivudine. HIV Clin Trials. 2012 Sep-Oct;13(5):233-44. doi: 10.1310/hct1305-233.

  PMID: 23134624 DERIVED

• Young B, Squires KE, Ross LL, Santiago L, Sloan LM, Zhao HH, Wine BC, Pakes GE, Margolis DA, Shaefer MS; Aries EPZ108859 Study Team. Inflammatory biomarker changes and their correlation with Framingham cardiovascular risk and lipid changes in antiretroviral-naive HIV-infected patients treated for 144 weeks with abacavir/lamivudine/atazanavir with or without ritonavir in ARIES. AIDS Res Hum Retroviruses. 2013 Feb;29(2):350-8. doi: 10.1089/aid.2012.0278. Epub 2012 Dec 5.

  PMID: 23039030 DERIVED

MeSH Terms

Conditions

Infections; HIV Infections

Interventions

abacavir; Atazanavir Sulfate; Ritonavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; 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

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

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: February 23, 2007
• First Posted: February 27, 2007
• Study Start: March 1, 2007
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: March 22, 2012
• Results First Posted: August 17, 2011

Record last verified: 2011-07

Locations

PR (4); CA (6); US (62)