Addition of Efavirenz or Nelfinavir to a Lamivudine/Zidovudine/Indinavir HIV Treatment Regimen
NCT ID: NCT00000903
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
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
444 participants
INTERVENTIONAL
2001-07-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Prior ACTG studies have shown that the 3-drug combination regimen (IDV/ZDV/3TC) resulted in improved clinical outcomes and therefore may prolong the effects of therapy. The enhanced effects seen with combination therapies are likely related to a greater suppression of RNA replication and alterations in resistance patterns. Due to the progressive success of combination regimens, it is possible that more potent regimens will further enhance viral suppression and provide more durable treatment responses. In light of the additive suppression of HIV replication determined by pharmacological, immunological, and virological results, nelfinavir (NFV) as an addition to IDV/ZDV/3TC will be evaluated. Based on the potency of nonnucleoside reverse transcriptase inhibitors (NNRTIs) to suppress viral replication and the effectiveness of 3-drug regimens containing NNRTIs, efavirenz (EFV) will also be evaluated as an addition to IDV/ZDV/3TC.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
The Effectiveness of Nelfinavir and Efavirenz, Used Alone or Together, Combined With Other Anti-HIV Drugs in Patients Who Have Taken Anti-HIV Drugs
NCT00001087
Virologic and Immunologic Activity of Continued Lamivudine (3TC) vs Delavirdine (DLV) in Combination With Indinavir (IDV) and Zidovudine (ZDV) or Stavudine (d4T) in 3TC-Experienced Subjects
NCT00000882
A Study to Compare The Ability of Different Anti-HIV Drugs to Decrease Viral Load After Nelfinavir (an Anti-HIV Drug)Treatment Failure
NCT00000918
A Study of the Effectiveness of Different Anti-HIV Treatments in HIV-Positive Individuals Who Have Been on a Protease Inhibitor-Containing Drug Regimen for at Least 16 Weeks
NCT00000914
Indinavir Plus Efavirenz Plus Adefovir Dipivoxil in HIV-Infected Patients Who Have Not Had Success With Nelfinavir
NCT00002220
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Patients with HIV infection, CD4 cell count less than or equal to 200 cells/mm3 or plasma HIV RNA greater than or equal to 100,000 copies/ml, and limited (no prior 3TC, NNRTI, or protease inhibitor) or no prior antiretroviral treatment are randomized to 1 of 3 arms. Patients are stratified by CD4 cell count (less than or equal to 50 cells/mm3 vs greater than 50 cells/mm3), HIV-1 RNA copy number (less than or equal to 40,000 copies/ml vs greater than 40,000 copies/ml), and prior antiretroviral therapy (no therapy vs any therapy), and then randomly assigned to 1 of 3 treatment arms:
Arm 1: 3TC plus ZDV plus IDV. Arm 2: 3TC plus ZDV plus IDV plus EFV. Arm 3: 3TC plus ZDV plus IDV plus NFV. Patients are followed for at least 72 weeks \[AS PER AMENDMENT 2/16/99: 96 weeks\] beyond the enrollment of the last patient. Patients who experience virologic relapse will have the option of continuing randomized study medications, switching to Step 2 treatment, switching to another ACTG study, or seeking best available therapy for the remaining weeks of the study. Step 2 treatment consists of abacavir or 2 NNRTIs plus efavirenz plus amprenavir or another protease inhibitor. \[AS PER AMENDMENT 4/3/00: Optimally, Step 2 treatment regimens should contain 3 or 4 drugs to which the virus is susceptible. If this is not possible, a drug to which the virus is partially susceptible is acceptable, but a drug to which the virus is resistant should not be included.\]
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.
TREATMENT
NONE
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Indinavir sulfate
Lamivudine/Zidovudine
Nelfinavir mesylate
Efavirenz
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
Allowed:
* Chemoprophylaxis for Pneumocystis carinii pneumonia.
* Topical and oral antifungal agents (except for oral ketoconazole and itraconazole).
* All antibiotics as clinically indicated (unless otherwise excluded).
* Treatment, maintenance, or chemoprophylaxis with approved agents for opportunistic infections as clinically indicated (unless otherwise excluded).
* Systemic corticosteroids for 21 days or less for acute problems.
* Recombinant erythropoietin (rEPO) and granulocyte colony-stimulating factor (G-CSF, filgrastim).
* Regularly prescribed medications such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives, megestrol acetate, testosterone.
* Alternative therapies such as vitamins. Patients should report the use of these therapies.
* \[AS PER AMENDMENT 2/16/99: Rifabutin can be administered at a reduced dose.\]
* \[AS PER AMENDMENT 4/3/00: Systemic cytotoxic chemotherapy. Study team should be notified.\]
* \[AS PER AMENDMENT 4/3/00: Expanded access and compassionate use drugs are allowed as part of Step 2 treatment only.\]
Allowed with caution:
* \[AS PER AMENDMENT 4/3/00: Viagra (sildenafil citrate) at a reduced dose unless otherwise approved by the protocol chair.\]
* \[AS PER AMENDMENT 4/3/00: Lovastatin or simvastatin with PIs is not recommended. Caution should be exercised with the use of all other statins when used concomitantly with PIs.\]
Concurrent Treatment:
Allowed:
* Alternative therapies such as acupuncture and visualization techniques. Patients should report use of these therapies.
Patients must have:
* Documented HIV-1 infection.
* CD4 count less than or equal to 200 cells/mm3 or a plasma HIV RNA greater than or equal to 100,000 copies/ml \[AS PER AMENDMENT 2/16/99:
* 80,000 copies/ml\] within 60 days prior to entry.
* Other lab values performed within 14 days prior to entry.
Prior Medication:
Allowed:
* Zidovudine (ZDV), didanosine (ddI), stavudine (d4T), or zalcitabine (ddC) therapy alone or in combination any time prior to study entry.
Exclusion Criteria
Excluded:
* All antiretroviral therapies other than study medications. \[AS PER AMENDMENT 4/3/00: Compassionate use and expanded access drugs are allowed as part of Step 2 treatment.\]
* Investigational drugs without specific approval from the Study Chair. \[AS PER AMENDMENT 4/3/00: Compassionate use and expanded access drugs are allowed as part of Step 2 treatment.\]
* Systemic cytotoxic chemotherapy. \[AS PER AMENDMENT 4/3/00: Systemic cytotoxic chemotherapy is allowed. Study team should be notified.\]
* Alprazolam, amiodarone, astemizole, bepridil, bupropion, cisapride, clorazepate, clozapine, diazepam, encainide, ergot alkaloids and derivatives of ergot alkaloids, estazolam, flecainide, flurazepam, itraconazole , ketoconazole, meperidine, midazolam, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, rifampin, terfenadine, triazolam, or zolpidem. \[AS PER AMENDMENT 2/16/99: Amiodarone, astemizole, cisapride, ergot alkaloids or drugs containing derivatives of ergot alkaloids, itraconazole, midazolam, triazolam, quinidine, rifampin, terfenadine.\] \[AS PER AMENDMENT 4/3/00: Amiodarone, astemizole, bepridil, cisapride, ergot alkaloids and derivatives of ergot alkaloids, Hypericum perforatum (St. John's wort), itraconazole, midazolam, quinidine, rifampin, terfenadine, triazolam.\]
* Vitamin E supplements. \[AS PER AMENDMENT 4/3/00: Multivitamins containing vitamin E are allowed.\]
Avoided:
* Herbal medications. Patients should report use.
Patients with the following prior conditions are excluded:
* Acute therapy for an infection or other medical illnesses within 14 days prior to study entry. \[AS PER AMENDMENT 2/16/99: Acute therapy for a serious infection or other serious medical illnesses that are potentially life-threatening and require systemic therapy and/or hospitalization within 14 days of study entry.\]
Prior Medication:
Excluded within 30 days prior to entry:
* More than 1 day experience with lamivudine (3TC), nonnucleoside reverse transcriptase inhibitor, or protease inhibitor.
* Erythropoietin, G-CSF, or GM-CSF.
* Interferons, interleukins, HIV vaccines, or any experimental therapy.
Excluded within 14 days prior to entry:
* Alprazolam (Xanax), amiodarone (Cordarone), astemizole (Hismanal), bepridil (Vascor), bupropion (Wellbutrin, Zyban), cisapride (Propulsid), clorazepate (Tranxene), clozapine (Clozaril), diazepam (Valium), encainide (Enkaid), ergot alkaloids or drugs containing derivatives of ergot alkaloids, estazolam (ProSom), flecainide (Tambocor), flurazepam (Dalmane), itraconazole (Sporanox), ketoconazole (Nizoral), meperidine (Demerol), midazolam (Versed), piroxicam (Feldene), propafenone (Rythmol), propoxyphene (Darvon, Darvocet), quinidine, rifabutin (Mycobutin), rifampin (Rifadin, Rifamate, Rifater, Rimactane), terfenadine (Seldane), triazolam (Halcion), or zolpidem (Ambien). \[AS PER AMENDMENT 2/16/99: Agents excluded within 14 days prior to entry are now as follows:
* amiodarone, astemizole, cisapride, ergot alkaloids or drugs containing derivatives of ergot alkaloids, itraconazole, midazolam, quinidine, rifampin, terfenadine, and triazolam.
Note:
* Rifabutin can be administered at a reduced dose of 150 mg/day.\]
13 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
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.
Margaret Fischl
Role: STUDY_CHAIR
Ann Collier
Role: STUDY_CHAIR
Judith Feinberg
Role: STUDY_CHAIR
Stefano Vella
Role: STUDY_CHAIR
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
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
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
Marin County Dept. of Health & Human Services, HIV/AIDS Program & Specialty Clinic
San Rafael, California, United States
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States
University of Colorado Hospital CRS
Aurora, Colorado, United States
Howard University Hosp., Div. of Infectious Diseases, ACTU
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
Queens Med. Ctr.
Honolulu, Hawaii, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States
Northwestern University CRS
Chicago, Illinois, United States
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States
Weiss Memorial Hosp.
Chicago, Illinois, United States
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
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
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, United States
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, 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
Cornell CRS
New York, New York, United States
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States
Cornell University A2201
New York, New York, United States
NY Univ. HIV/AIDS CRS
New York, New York, United States
Weill Med. College of Cornell Univ., The Cornell CTU
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
Unc Aids Crs
Chapel Hill, North Carolina, United States
Carolinas HealthCare System, Carolinas Med. Ctr.
Charlotte, 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
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States
University of Washington AIDS CRS
Seattle, Washington, United States
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.
Fischl MA, Ribaudo HJ, Collier AC, Erice A, Giuliano M, Dehlinger M, Eron JJ Jr, Saag MS, Hammer SM, Vella S, Morse GD, Feinberg JE, Demeter LM, Eshleman SH; Adult AIDS Clinical Trials Group 388 Study Team. A randomized trial of 2 different 4-drug antiretroviral regimens versus a 3-drug regimen, in advanced human immunodeficiency virus disease. J Infect Dis. 2003 Sep 1;188(5):625-34. doi: 10.1086/377311. Epub 2003 Aug 15.
Demeter LM, Ribaudo HJ, Erice A, Eshleman SH, Hammer SM, Hellmann NS, Fischl MA; AIDS Clinical Trials Group Protocol 388. HIV-1 drug resistance in subjects with advanced HIV-1 infection in whom antiretroviral combination therapy is failing: a substudy of AIDS Clinical Trials Group Protocol 388. Clin Infect Dis. 2004 Aug 15;39(4):552-8. doi: 10.1086/422518. Epub 2004 Jul 30.
DiCenzo R, Forrest A, Fischl MA, Collier A, Feinberg J, Ribaudo H, DiFrancecso R, Morse GD; AIDS Clinical Trials Group 388/733/5060 Study Team. Pharmacokinetics of indinavir and nelfinavir in treatment-naive, human immunodeficiency virus-infected subjects. Antimicrob Agents Chemother. 2004 Mar;48(3):918-23. doi: 10.1128/AAC.48.3.918-923.2004.
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.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
11347
Identifier Type: REGISTRY
Identifier Source: secondary_id
Substudy ACTG 734
Identifier Type: -
Identifier Source: secondary_id
Substudy ACTG A5060s
Identifier Type: -
Identifier Source: secondary_id
Substudy ACTG 732
Identifier Type: -
Identifier Source: secondary_id
Substudy ACTG 733
Identifier Type: -
Identifier Source: secondary_id
Substudy ACTG 735
Identifier Type: -
Identifier Source: secondary_id
Substudy ACTG 737
Identifier Type: -
Identifier Source: secondary_id
Substudy ACTG 746
Identifier Type: -
Identifier Source: secondary_id
ACTG 388
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.