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

NCT ID: NCT00440947

Last Updated: 2012-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 515 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2010-07-31

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.

Detailed Description

Safety and Efficacy of an Initial Regimen of Atazanavir (ATV) + Ritonavir (/r) + the Abacavir/Lamivudine Fixed-Dose Combination Tablet (ABC/3TC FDC) for 36 weeks followed by Simplification to Atazanavir with ABC/3TC FDC or Maintenance of the Initial Regimen for an Additional 48 weeks in Antiretroviral-Naive HIV-1 Infected HLA-B*5701 Negative Subjects followed by an Optional 60-Week Treatment Extension Phase

Conditions

Infection, Human Immunodeficiency Virus I; HIV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Simplification

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.

Group Type: OTHER

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

Intervention Type: 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

Continuation

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.

Group Type: OTHER

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

Intervention Type: 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

Interventions

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

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

Intervention Type: DRUG

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

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Hypersensitivity to any component of the study drugs.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN).
• Total bilirubin > 1.5 times the upper limit of normal (ULN).
• Subject has 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. Any grade 4 laboratory abnormality would exclude a subject from study participation.
• Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to screening, or has an anticipated need for these agents within the study period.
• Enrolled in one or more investigational drug protocols, which may have impacted HIV-1 RNA suppression.
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
• Subjects requiring concomitant administration of proton pump inhibitors.
• Subjects who require treatment with the prohibited medications within 28 days of commencement of investigational product, or an anticipated need during the study.

Eligibility Criteria for Treatment Extension Phase:

-Subjects will be eligible to continue in the treatment extension phase (Weeks 84 to 144) if they have successfully completed the 84-week study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Long Beach, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Newport Beach, California, United States

GSK Investigational Site

Oakland, California, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

Glastonbury, Connecticut, United States

GSK Investigational Site

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

GSK Investigational Site

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

GSK Investigational Site

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

GSK Investigational Site

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

GSK Investigational Site

Fort Lauderdale, Florida, United States

GSK Investigational Site

Fort Lauderdale, Florida, United States

GSK Investigational Site

Fort Lauderdale, Florida, United States

GSK Investigational Site

Ft. Pierce, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Orlando, Florida, United States

GSK Investigational Site

Plantation, Florida, United States

GSK Investigational Site

Sarasota, Florida, United States

GSK Investigational Site

Tampa, Florida, United States

GSK Investigational Site

Tampa, Florida, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Augusta, Georgia, United States

GSK Investigational Site

Decatur, Georgia, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Maywood, Illinois, United States

GSK Investigational Site

Lexington, Kentucky, United States

GSK Investigational Site

Baltimore, Maryland, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Detroit, Michigan, United States

GSK Investigational Site

Minneapolis, Minnesota, United States

GSK Investigational Site

Minneapolis, Minnesota, United States

GSK Investigational Site

St Louis, Missouri, United States

GSK Investigational Site

Hillsborough, New Jersey, United States

GSK Investigational Site

Newark, New Jersey, United States

GSK Investigational Site

Somers Point, New Jersey, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Valhalla, New York, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Greenville, North Carolina, United States

GSK Investigational Site

Akron, Ohio, United States

GSK Investigational Site

Toledo, Ohio, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Providence, Rhode Island, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

El Paso, Texas, United States

GSK Investigational Site

Fort Worth, Texas, United States

GSK Investigational Site

Galveston, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Longview, Texas, United States

GSK Investigational Site

Annandale, Virginia, United States

GSK Investigational Site

Norfolk, Virginia, United States

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Ponce, , Puerto Rico

GSK Investigational Site

Ponce, , Puerto Rico

GSK Investigational Site

San Juan, , Puerto Rico

GSK Investigational Site

San Juan, , Puerto Rico

Countries

United States; Canada; Puerto Rico

References

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.

Reference Type: 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.

Reference Type: BACKGROUND

PMID: 18670229 (View on PubMed)

• 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.

Reference Type: 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.

Reference Type: 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.

Reference Type: 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

Reference Type: 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.

Reference Type: BACKGROUND

PMID: 20542844 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20613461 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24586911 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23134624 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23039030 (View on PubMed)

Other Identifiers

EPZ108859

Identifier Type: -

Identifier Source: org_study_id