Comparative Study of Three NNRTI-Sparing HAART Regimens
NCT ID: NCT00811954
Last Updated: 2014-09-05
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
1814 participants
INTERVENTIONAL
2009-05-31
2013-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
This study was designed to look at how well different combinations of anti-HIV drugs work to decrease the amount of HIV in the blood (viral load) of and allow immune system recovery in people who have never received anti-HIV therapy. This study also examined drug tolerability and safety for the various drug combinations.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Study of Darunavir/r + Tenofovir/Emtricitabine vs. Darunavir/r + Raltegravir in HIV-infected Antiretroviral naïve Subjects
NCT01066962
Once Daily Antiretroviral Therapy in HIV Infected Adults Treated With HAART
NCT00196612
Effects of Intensive cART During Acute/Early HIV Infection
NCT01154673
Pilot Study of Raltegravir/Truvada Versus Efavirenz/Truvada for Adults With Acute IV-1 Infection
NCT00734344
Raltegravir (Isentress/MK-0518) and HIV-1 Infected CD4 Cells During Acute/Early HIV-1
NCT00781287
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
According to data, an efavirenz (EFV)-containing regimen (2 NRTIs + 1 NNRTI, with EFVas the NNRTI) requires fewer pills for the patient, has mild and few side effects, and is more effective in reducing viral load than other regimens, making it the preferred choice for most patients. However, for some patients, an EFV-containing regimen is not feasible due to side effects, acquired NNRTI-resistant HIV virus, or other undesirable effects. For these patients, it is necessary to find alternative regimens with comparable safety and efficacy. This study examined how well different combinations of anti-HIV drugs work, including safety and drug tolerability for various combinations.
This was a phase III, prospective, randomized study. Participants was randomly assigned to one of three different groups (treatment arms)-A, B, or C -each representing a different drug combination regimen, none of which contained an NNRTI.
Arm A: Atazanavir (ATV) + Ritonavir (RTV) + Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)
Arm B: Raltegravir (RAL) + FTC/TDF
Arm C: Darunavir (DRV) + RTV + FTC/TDF
The duration of this study was between 96 and 192 weeks, depending on when the participant enrolled. There were a total of 1,809 participants, approximately 600 per treatment arm. Screening and pre-entry evaluations must occur prior to the participant starting any study medication, treatments, or interventions. Participants were randomly assigned to their treatment groups at the entry visit and must begin treatment within 72 hours of randomization. Participants was told which group they were in and what medications they were administered. The study drugs were distributed at entry. All drugs were provided by the study with the exception of RTV, which would have to be obtained through the participant's primary care physician (Group A or C). If a participant was unable to tolerate any of the study medications during the course of the study then their doctor could switch them to another regimen.
During the study, participants was asked to return to the clinic at Weeks 4, 8, 16, 24, 36, and 48 and then every 16 weeks until the end of the study. They were also contacted by telephone during Week 2 to check on their status. Visits were last about 1 hour. At most visits, participants had a physical exam and answered questions about any medications they were taken. Additionally, participants completed questionnaires addressing their smoking and alcohol habits, had blood drawn, and were asked to give urine samples. At some visits, participants had to come to the clinic without having eaten for 8 hours. If the participant was female and able to become pregnant, a pregnancy test might be given at any visit if pregnancy was suspected.
Some participants of A5257 were asked to participate in an optional metabolic substudy A5260s. This substudy took place at only some study sites and continued last up to 144 weeks, including time on A5257. The primary focus of this substudy was to examine carotid artery intima-media thickness (CIMT) as it relates to both RTV- and RAL-containing regimens. Randomization, stratification, treatment assignments, and study visits were as per A5257.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm A: ATV/RTV + FTC/TDF
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.
Emtricitabine/tenofovir disoproxil fumarate
200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally daily. A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs).
Ritonavir
100 mg taken orally once daily. A protease inhibitor (PI).
Atazanavir
300 mg taken orally once daily. A protease inhibitor (PI).
Arm B: RAL + FTC/TDF
FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily.
Emtricitabine/tenofovir disoproxil fumarate
200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally daily. A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs).
Raltegravir
400 mg taken orally twice daily. An integrase inhibitor (INI).
Arm C: DRV/RTV + FTC/TDF
FTC/TDF, darunavir (DRV), and RTV, orally, once daily.
Emtricitabine/tenofovir disoproxil fumarate
200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally daily. A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs).
Darunavir
800 mg taken orally once daily. A protease inhibitor (PI).
Ritonavir
100 mg taken orally once daily. A protease inhibitor (PI).
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Emtricitabine/tenofovir disoproxil fumarate
200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally daily. A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs).
Raltegravir
400 mg taken orally twice daily. An integrase inhibitor (INI).
Darunavir
800 mg taken orally once daily. A protease inhibitor (PI).
Ritonavir
100 mg taken orally once daily. A protease inhibitor (PI).
Atazanavir
300 mg taken orally once daily. A protease inhibitor (PI).
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* No evidence of any exclusionary mutations defined as any major NRTI or PI resistance-associated mutation on any genotype or evidence of significant NRTI or PI resistance on any phenotype performed at any time prior to study entry. NNRTI-associated resistance mutations are not excluded. More information on this criterion can be found in the study protocol.
* No prior anti-HIV therapy. More information on this criterion can be found in the study protocol.
* Viral load is 1000 copies/mL or higher, as measured within 90 days prior to study entry
* Certain laboratory values obtained within 60 days prior to study entry
* Ability to obtain RTV by prescription
* Completed cardiovascular risk assessment. More information on this criterion can be found in the study protocol.
* Must agree to use acceptable forms of contraception while receiving study drugs and for 6 weeks after stopping the medications. More information on this criterion is available in the protocol.
* Negative pregnancy test within 72 hours before initiating antiretroviral medication
* Participating in research at any AIDS Clinical Trial Group (ACTG) clinical research site or select International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group sites
* Ability and willingness of subject or legal guardian/representative to give written informed consent
Exclusion Criteria
* Known allergy or sensitivity to study drugs or their ingredients. A history of sulfa allergy is not excluded.
* Any condition that, in the opinion of the investigator, would compromise the participant's ability to participate in the study
* Serious illness requiring systemic treatment and/or hospitalization until participant either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 7 days prior to study entry
* Requirement for any current medications that are prohibited with any study drugs
* Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness
* Any prior use of entecavir for treatment of hepatitis B for greater than 8 weeks while the participant was known to be HIV infected
* Presence of decompensated cirrhosis
* Pregnant or breastfeeding
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Bristol-Myers Squibb
INDUSTRY
Gilead Sciences
INDUSTRY
Merck Sharp & Dohme LLC
INDUSTRY
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
INDUSTRY
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
NETWORK
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Jeffrey L. Lennox, MD
Role: STUDY_CHAIR
Emory HIV/AIDS CTU
Judith Silverstein Currier, MD, MSc
Role: STUDY_CHAIR
UCLA AIDS Prevention & Treatment CTU
Raphael Landovitz, MD, MSc
Role: STUDY_CHAIR
UCLA AIDS Prevention & Treatment CTU
Igho Ofotokun, MD
Role: STUDY_CHAIR
Emory HIV/AIDS CTU
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Alabama Therapeutics CRS
Birmingham, Alabama, United States
Miller Children's Hospital
Long Beach, California, United States
USC CRS
Los Angeles, California, United States
UCLA CARE Center CRS
Los Angeles, California, United States
Stanford CRS
Palo Alto, California, United States
Ucsd, Avrc Crs
San Diego, California, United States
Ucsf Aids Crs
San Francisco, California, United States
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States
University of Colorado Hospital CRS
Aurora, Colorado, United States
Denver Public Health CRS
Denver, Colorado, United States
Georgetown University CRS (GU CRS)
Washington D.C., District of Columbia, United States
Howard Univ. Washington DC NICHD CRS
Washington D.C., District of Columbia, United States
South Florida Childrens Diagnostic & Treatment Cen (5055)
Fort Lauderdale, Florida, United States
University of Florida Jacksonville (5051)
Jacksonville, Florida, United States
Univ. of Miami AIDS CRS
Miami, Florida, United States
The Ponce de Leon Center CRS
Atlanta, Georgia, United States
Northwestern University CRS
Chicago, Illinois, United States
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States
Tulane University New Orleans NICHD CRS (5095)
New Orleans, Louisiana, United States
IHV Baltimore Treatment CRS
Baltimore, Maryland, United States
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States
Massachusetts General Hospital CRS
Boston, Massachusetts, United States
Brigham and Women's Hosp. ACTG CRS
Boston, Massachusetts, United States
Bmc Actg Crs
Boston, Massachusetts, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States
Wayne State Univ. CRS
Detroit, Michigan, United States
Henry Ford Hosp. CRS
Detroit, Michigan, United States
Washington U CRS
St Louis, Missouri, United States
Cooper Univ. Hosp. CRS
Camden, New Jersey, United States
New Jersey Medical School- Adult Clinical Research Ctr. CRS
Newark, New Jersey, United States
Cornell CRS
New York, New York, United States
NY Univ. HIV/AIDS CRS
New York, New York, United States
Metropolitan Hospital
New York, New York, United States
HIV Prevention & Treatment CRS
New York, New York, United States
AIDS Care CRS
Rochester, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
SUNY Stony Brook NICHD CRS (5040)
Stony Brook, New York, United States
Bronx-Lebanon Hosp. Ctr. CRS
The Bronx, New York, United States
Unc Aids Crs
Chapel Hill, North Carolina, United States
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States
Regional Center for Infectious Disease, Wendover Medical Center CRS (3203)
Greensboro, North Carolina, United States
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States
Case CRS
Cleveland, Ohio, United States
Metro Health CRS
Cleveland, Ohio, United States
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States
The Research & Education Group- Portland CRS (31474)
Portland, Oregon, United States
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States
Pitt CRS
Pittsburgh, Pennsylvania, United States
The Miriam Hosp. ACTG CRS
Providence, Rhode Island, United States
St. Jude/UTHSC CRS
Memphis, Tennessee, United States
Vanderbilt Therapeutics CRS
Nashville, Tennessee, United States
Trinity Health and Wellness Center
Dallas, Texas, United States
Houston AIDS Research Team CRS
Houston, Texas, United States
Virginia Commonwealth Univ. Medical Ctr. CRS
Richmond, Virginia, United States
University of Washington AIDS CRS
Seattle, Washington, United States
San Juan City Hosp. PR NICHD CRS
Rio Piedras, , Puerto Rico
Puerto Rico-AIDS CRS
San Juan, , Puerto Rico
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Bartlett JA, Chen SS, Quinn JB. Comparative efficacy of nucleoside/nucleotide reverse transcriptase inhibitors in combination with efavirenz: results of a systematic overview. HIV Clin Trials. 2007 Jul-Aug;8(4):221-6. doi: 10.1310/hct0804-221.
Duvivier C, Ghosn J, Assoumou L, Soulie C, Peytavin G, Calvez V, Genin MA, Molina JM, Bouchaud O, Katlama C, Costagliola D; ANRS 121 study group. Initial therapy with nucleoside reverse transcriptase inhibitor-containing regimens is more effective than with regimens that spare them with no difference in short-term fat distribution: Hippocampe-ANRS 121 Trial. J Antimicrob Chemother. 2008 Oct;62(4):797-808. doi: 10.1093/jac/dkn278. Epub 2008 Jul 18.
Markowitz M, Nguyen BY, Gotuzzo E, Mendo F, Ratanasuwan W, Kovacs C, Prada G, Morales-Ramirez JO, Crumpacker CS, Isaacs RD, Gilde LR, Wan H, Miller MD, Wenning LA, Teppler H; Protocol 004 Part II Study Team. Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr. 2007 Oct 1;46(2):125-33. doi: 10.1097/QAI.0b013e318157131c.
Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, Moyle G, Mancini M, Percival L, Yang R, Thiry A, McGrath D; CASTLE Study Team. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet. 2008 Aug 23;372(9639):646-55. doi: 10.1016/S0140-6736(08)61081-8.
Hughey CM, Vuong BW, Ribaudo HB, Mitchell CCK, Korcarz CE, Hodis HN, Currier JS, Stein JH. Grayscale Ultrasound Texture Features of Carotid and Brachial Arteries in People With HIV Infection Before and After Antiretroviral Therapy. J Am Heart Assoc. 2022 Mar;11(5):e024142. doi: 10.1161/JAHA.121.024142. Epub 2022 Feb 18.
Li B, Veturi Y, Verma A, Bradford Y, Daar ES, Gulick RM, Riddler SA, Robbins GK, Lennox JL, Haas DW, Ritchie MD. Tissue specificity-aware TWAS (TSA-TWAS) framework identifies novel associations with metabolic, immunologic, and virologic traits in HIV-positive adults. PLoS Genet. 2021 Apr 26;17(4):e1009464. doi: 10.1371/journal.pgen.1009464. eCollection 2021 Apr.
Bares SH, Smeaton LM, Scott SE, Smith BA, Godfrey C, McComsey GA. The Association Between Weight Gain, Sex, and Immune Activation Following the Initiation of Antiretroviral Therapy. J Infect Dis. 2021 Nov 22;224(10):1765-1774. doi: 10.1093/infdis/jiab210.
McComsey GA, Moser C, Currier J, Ribaudo HJ, Paczuski P, Dube MP, Kelesidis T, Rothenberg J, Stein JH, Brown TT. Body Composition Changes After Initiation of Raltegravir or Protease Inhibitors: ACTG A5260s. Clin Infect Dis. 2016 Apr 1;62(7):853-62. doi: 10.1093/cid/ciw017. Epub 2016 Jan 20.
Kelesidis T, Tran TT, Stein JH, Brown TT, Moser C, Ribaudo HJ, Dube MP, Murphy R, Yang OO, Currier JS, McComsey GA. Changes in Inflammation and Immune Activation With Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s. Clin Infect Dis. 2015 Aug 15;61(4):651-60. doi: 10.1093/cid/civ327. Epub 2015 Apr 22.
Ofotokun I, Na LH, Landovitz RJ, Ribaudo HJ, McComsey GA, Godfrey C, Aweeka F, Cohn SE, Sagar M, Kuritzkes DR, Brown TT, Patterson KB, Para MF, Leavitt RY, Villasis-Keever A, Baugh BP, Lennox JL, Currier JS; AIDS Clinical Trials Group (ACTG) A5257 Team. Comparison of the metabolic effects of ritonavir-boosted darunavir or atazanavir versus raltegravir, and the impact of ritonavir plasma exposure: ACTG 5257. Clin Infect Dis. 2015 Jun 15;60(12):1842-51. doi: 10.1093/cid/civ193. Epub 2015 Mar 12.
Lennox JL, Landovitz RJ, Ribaudo HJ, Ofotokun I, Na LH, Godfrey C, Kuritzkes DR, Sagar M, Brown TT, Cohn SE, McComsey GA, Aweeka F, Fichtenbaum CJ, Presti RM, Koletar SL, Haas DW, Patterson KB, Benson CA, Baugh BP, Leavitt RY, Rooney JF, Seekins D, Currier JS; ACTG A5257 Team. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med. 2014 Oct 7;161(7):461-71. doi: 10.7326/M14-1084.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
ACTG A5257
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.