Comparison of Three Different Initial Treatments Without Protease Inhibitors for HIV Infection
NCT ID: NCT00013520
Last Updated: 2012-05-21
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE3
1125 participants
INTERVENTIONAL
2005-06-30
Brief Summary
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The current rule for starting treatment of HIV infection is to combine members from different classes of anti-HIV drugs, such as 2 nucleoside reverse transcriptase inhibitors (NRTIs) and either a PI or a nonnucleoside reverse transcriptase inhibitor (NNRTI). However, these combinations can be complicated and difficult to take, can cause a number of side effects, and may become ineffective. Combinations that are simpler, better tolerated, and more effective are needed. Because PIs can cause long-term side effects and because HIV can become resistant to many of them at the same time, anti-HIV combination treatments that do not use PIs are being tested.
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Detailed Description
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Participants will be in this study for a minimum of 120 weeks and a maximum of approximately 4 years. In Step 1, patients are randomly selected to receive 1 of 3 blinded treatment regimens: abacavir (ABC)/lamivudine (3TC)/zidovudine (ZDV)/efavirenz (EFV), ABC/3TC/ZDV, or 3TC/ZDV/EFV. Patients with confirmed virologic failure on Step 1 and two successive plasma HIV RNA levels of 10,000 copies/ml or greater must register to Step 2. Patients with confirmed virologic failure on Step 1 and whose plasma HIV RNA is under 10,000 copies/ml may remain on Step 1 or register to Step 2. \[AS PER AMENDMENT 04/11/03: Discontinuation of Arm B was recommended. Consequently, Arms A and C were unblinded to EFV but not to ABC. A number of options are available for patients originally randomized to Arm B.\]
Step 2 is open label. Regimens include 2 or 3 nucleoside reverse transcriptase inhibitors (NRTIs) in combination with EFV, atazanavir (ATZ), ritonavir-boosted ATZ, or tenofovir disoproxil fumarate (TDF). Patients on Arm B treatment who have an HIV RNA level less than 200 copies/ml within the past 8 weeks are eligible for randomization to open-label intensification of Arm B on Step 3.
Step 3 regimens include ABC/3TC/ZDV plus either EFV or TDF. Patients with evidence of treatment-limiting toxicity to Step 3 study drugs have the option of substituting d4T for ZDV, ddI for ABC or TDF, and/or NVP for EFV. Patients with confirmed virologic failure on Step 3 and whose plasma HIV RNA is less than 10,000 copies/ml may either remain on Step 3 or register to Step 4. Patients with two successive plasma HIV RNA levels of 10,000 copies/ml or greater on Step 3 must register to Step 4.
Step 4 is open label. Regimens include two or three NRTIs plus EFV, ATV, ritonavir-boosted ATV, or TDF. Clinical assessments and laboratory evaluations are done at entry, at Weeks 2, 4, 6, 8, 12, 16, 20, 24, and then every 8 weeks thereafter for the duration of the study. Evaluations are also required when a protocol-allowed drug substitution is made.
In addition, 3 substudies are being conducted: a neurology substudy for efavirenz, a pharmacology substudy for atazanavir, and a viral dynamics substudy.
Conditions
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Study Design
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TREATMENT
Interventions
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Abacavir sulfate, Lamivudine and Zidovudine
Atazanavir
Lamivudine/Zidovudine
Abacavir sulfate
Efavirenz
Nevirapine
Lamivudine
Stavudine
Zidovudine
Didanosine
Eligibility Criteria
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Inclusion Criteria
* Are HIV-positive.
* Have a viral load of at least 400 copies/ml within 90 days prior to study entry.
* Are at least 16 years old.
* Weigh at least 40 kg.
* Have a negative pregnancy test within 48 hours before starting study drugs, if female and able to have children.
* Agree to use 2 effective methods of birth control while taking, and for 3 months after stopping, the study medications.
* Provide written consent of a parent or guardian, if under 18 years of age.
Exclusion Criteria
* Have taken anti-HIV drugs in the past.
* Are allergic to any of the study drugs or ingredients.
* Are pregnant or breast-feeding.
* Have taken any of the following drugs within 14 days prior to study entry: amiodarone, astemizole, bepridil, cisapride, ergot or ergot derivatives, systemic itraconazole, systemic ketoconazole, midazolam, propoxyphene, quinidine, rifampin, terfenadine, thalidomide, triazolam, or St. John's wort.
* Have taken drugs that influence the immune system, HIV or other vaccines, or investigational drugs within 30 days prior to study entry. Prednisone at a dose of 10 mg or less daily is allowed.
* Have taken drugs or been hospitalized for serious infections or medical illnesses within 14 days prior to study entry.
* Have growths or tumors that require drug therapy.
* Have Pneumocystis carinii pneumonia that is not clinically stable and whose treatment is not completed at least 7 days prior to study entry.
* Have infections or medical illnesses that are not under control or that have not received complete treatment before study entry.
* Have any condition that, in the opinion of the investigator, would prevent them from properly participating in the study.
* Abuse drugs or alcohol.
* This study has been updated to exclude patients who are receiving systemic itraconazole and rifabutin.
16 Years
ALL
No
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Roy Gulick, MD
Role: STUDY_CHAIR
Cecilia Shikuma, MD
Role: STUDY_CHAIR
Locations
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Alabama Therapeutics CRS
Birmingham, Alabama, 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
UC Davis Medical Center
Sacramento, California, United States
Univ. of California Davis Med. Ctr., ACTU
Sacramento, California, United States
Ucsd, Avrc Crs
San Diego, California, United States
Ucsf Aids Crs
San Francisco, California, United States
Santa Clara Valley Med. Ctr.
San Jose, California, United States
San Mateo County AIDS Program
San Mateo, California, United States
Willow Clinic A0507 CRS
San Mateo, California, United States
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States
University of Colorado Hospital CRS
Aurora, Colorado, United States
Georgetown University CRS (GU CRS)
Washington D.C., District of Columbia, United States
Univ. of Miami AIDS CRS
Miami, Florida, United States
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States
Northwestern University CRS
Chicago, Illinois, United States
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana, United States
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States
Univ. of Iowa Healthcare, Div. of Infectious Diseases
Iowa City, Iowa, United States
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States
Bmc Actg Crs
Boston, Massachusetts, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States
Brigham and Women's Hosp. ACTG CRS
Boston, Massachusetts, United States
SSTAR, Family Healthcare Ctr.
Fall River, Massachusetts, United States
University of Minnesota, ACTU
Minneapolis, Minnesota, United States
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States
Washington U CRS
St Louis, Missouri, United States
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
Omaha, Nebraska, United States
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States
Beth Israel Med. Ctr., ACTU
New York, New York, United States
Weill Med. College of Cornell Univ., The Cornell CTU
New York, New York, United States
NY Univ. HIV/AIDS CRS
New York, New York, United States
Cornell CRS
New York, New York, United States
Columbia Univ., HIV Prevention and Treatment Medical Ctr.
New York, New York, United States
HIV Prevention & Treatment CRS
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
AIDS Care CRS
Rochester, New York, United States
McCree McCuller Wellness Ctr. at the Connection, Infectious Disease Unit
Rochester, 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
Greensboro, North Carolina, United States
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States
Case CRS
Cleveland, Ohio, United States
MetroHealth CRS
Cleveland, Ohio, United States
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States
Philadelphia Veterans Admin. Med. Ctr. A6205 CRS
Philadelphia, Pennsylvania, United States
Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.
Philadelphia, Pennsylvania, 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
Rhode Island Hosp.
Providence, Rhode Island, United States
Vanderbilt Therapeutics CRS
Nashville, Tennessee, United States
University of Washington AIDS CRS
Seattle, Washington, United States
Puerto Rico-AIDS CRS
San Juan, , Puerto Rico
Countries
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References
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H Ribaudo, D Clifford, R Gulick, C Shikuma, K Klingman, S Snyder, and E Acosta. Relationships between Efavirenz Pharmacokinetics, Side Effects, Drug Discontinuation, Virologic Response, and Race: Results from ACTG A5095/A5097s. CROI 2004. Abstract 132.
Feinberg J. Meeting notes from the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment. Trizivir vs. efavirenz: results from ACTG 5095. AIDS Clin Care. 2003 Sep;15(9):78-9.
Gulick RM, Ribaudo HJ, Shikuma CM, Lustgarten S, Squires KE, Meyer WA 3rd, Acosta EP, Schackman BR, Pilcher CD, Murphy RL, Maher WE, Witt MD, Reichman RC, Snyder S, Klingman KL, Kuritzkes DR; AIDS Clinical Trials Group Study A5095 Team. Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. N Engl J Med. 2004 Apr 29;350(18):1850-61. doi: 10.1056/NEJMoa031772.
Clifford DB, Evans S, Yang Y, Acosta EP, Goodkin K, Tashima K, Simpson D, Dorfman D, Ribaudo H, Gulick RM. Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Ann Intern Med. 2005 Nov 15;143(10):714-21. doi: 10.7326/0003-4819-143-10-200511150-00008.
Gulick RM, Ribaudo HJ, Shikuma CM, Lalama C, Schackman BR, Meyer WA 3rd, Acosta EP, Schouten J, Squires KE, Pilcher CD, Murphy RL, Koletar SL, Carlson M, Reichman RC, Bastow B, Klingman KL, Kuritzkes DR; AIDS Clinical Trials Group (ACTG) A5095 Study Team. Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial. JAMA. 2006 Aug 16;296(7):769-81. doi: 10.1001/jama.296.7.769.
Ribaudo HJ, Kuritzkes DR, Schackman BR, Acosta EP, Shikuma CM, Gulick RM. Design issues in initial HIV-treatment trials: focus on ACTG A5095. Antivir Ther. 2006;11(6):751-60.
Kuritzkes DR, Ribaudo HJ, Squires KE, Koletar SL, Santana J, Riddler SA, Reichman R, Shikuma C, Meyer WA 3rd, Klingman KL, Gulick RM; ACTG A5166s Protocol Team. Plasma HIV-1 RNA dynamics in antiretroviral-naive subjects receiving either triple-nucleoside or efavirenz-containing regimens: ACTG A5166s. J Infect Dis. 2007 Apr 15;195(8):1169-76. doi: 10.1086/512619. Epub 2007 Mar 6.
Schackman BR, Ribaudo HJ, Krambrink A, Hughes V, Kuritzkes DR, Gulick RM. Racial differences in virologic failure associated with adherence and quality of life on efavirenz-containing regimens for initial HIV therapy: results of ACTG A5095. J Acquir Immune Defic Syndr. 2007 Dec 15;46(5):547-54. doi: 10.1097/qai.0b013e31815ac499.
Paredes R, Lalama CM, Ribaudo HJ, Schackman BR, Shikuma C, Giguel F, Meyer WA 3rd, Johnson VA, Fiscus SA, D'Aquila RT, Gulick RM, Kuritzkes DR; AIDS Clinical Trials Group (ACTG) A5095 Study Team. Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. J Infect Dis. 2010 Mar;201(5):662-71. doi: 10.1086/650543.
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.
Leonard MA, Cindi Z, Bradford Y, Bourgi K, Koethe J, Turner M, Norwood J, Woodward B, Erdem H, Basham R, Baker P, Rebeiro PF, Sterling TR, Hulgan T, Daar ES, Gulick R, Riddler SA, Sinxadi P, Ritchie MD, Haas DW. Efavirenz Pharmacogenetics and Weight Gain Following Switch to Integrase Inhibitor-Containing Regimens. Clin Infect Dis. 2021 Oct 5;73(7):e2153-e2163. doi: 10.1093/cid/ciaa1219.
Mollan KR, Smurzynski M, Eron JJ, Daar ES, Campbell TB, Sax PE, Gulick RM, Na L, O'Keefe L, Robertson KR, Tierney C. Association between efavirenz as initial therapy for HIV-1 infection and increased risk for suicidal ideation or attempted or completed suicide: an analysis of trial data. Ann Intern Med. 2014 Jul 1;161(1):1-10. doi: 10.7326/M14-0293.
Lok JJ, Hunt PW, Collier AC, Benson CA, Witt MD, Luque AE, Deeks SG, Bosch RJ. The impact of age on the prognostic capacity of CD8+ T-cell activation during suppressive antiretroviral therapy. AIDS. 2013 Aug 24;27(13):2101-10. doi: 10.1097/QAD.0b013e32836191b1.
Schouten JT, Krambrink A, Ribaudo HJ, Kmack A, Webb N, Shikuma C, Kuritzkes DR, Gulick RM. Substitution of nevirapine because of efavirenz toxicity in AIDS clinical trials group A5095. Clin Infect Dis. 2010 Mar 1;50(5):787-91. doi: 10.1086/650539.
Other Identifiers
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10212
Identifier Type: REGISTRY
Identifier Source: secondary_id
ACTG A5095
Identifier Type: -
Identifier Source: secondary_id
AACTG A5095
Identifier Type: -
Identifier Source: secondary_id
Substudy ACTG A5097s
Identifier Type: -
Identifier Source: secondary_id
Substudy AACTG 5107s
Identifier Type: -
Identifier Source: secondary_id
Substudy AACTG 5166s
Identifier Type: -
Identifier Source: secondary_id
Substudy ACTG A5166s
Identifier Type: -
Identifier Source: secondary_id
Substudy AACTG 5097s
Identifier Type: -
Identifier Source: secondary_id
Substudy ACTG A5107s
Identifier Type: -
Identifier Source: secondary_id
A5095
Identifier Type: -
Identifier Source: org_study_id
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