Addition of Efavirenz or Nelfinavir to a Lamivudine/Zidovudine/Indinavir HIV Treatment Regimen
A Phase III Randomized, Controlled Trial of Efavirenz (EFV) or Nelfinavir (NFV) in Combination With Fixed-Dose Combination Lamivudine/Zidovudine (3TC/ZDV) and Indinavir (IDV) in HIV-Infected Subjects With Less Than or Equal to 200 CD4 Cells/mm3 or Greater Than or Equal to 80,000 HIV RNA Copies/ml in Plasma
9 other identifiers
interventional
444
2 countries
50
Brief Summary
To compare time to a virologic failure (first of 2 consecutive plasma HIV RNA levels greater than or equal to 200 copies/ml at or after Week 24) of each 4-drug regimen vs the 3-drug regimen. To determine the safety, tolerance, and virologic benefits of either nelfinavir (NFV) or efavirenz (EFV) with indinavir/lamivudine/zidovudine (IDV/3TC/ZDV) vs IDV/3TC/ZDV alone, in the treatment of patients with advanced HIV disease who have received limited or no prior antiretroviral therapy. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 hiv-infections
50 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 2, 1999
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2001
CompletedFirst Posted
Study publicly available on registry
August 31, 2001
CompletedMay 21, 2012
May 1, 2012
November 2, 1999
May 17, 2012
Conditions
Keywords
Interventions
Eligibility Criteria
You may qualify if:
- Concurrent Medication:
- 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:
- \[AS PER AMENDMENT 4/3/00: Viagra (sildenafil citrate) at a reduced dose unless otherwise approved by the protocol chair.\]
- +12 more criteria
You may not qualify if:
- Concurrent Medication:
- 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.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (50)
Alabama Therapeutics CRS
Birmingham, Alabama, 35294, United States
USC CRS
Los Angeles, California, 900331079, United States
UCLA CARE Center CRS
Los Angeles, California, 90095, United States
Stanford CRS
Palo Alto, California, United States
Ucsd, Avrc Crs
San Diego, California, 92161, United States
Ucsf Aids Crs
San Francisco, California, 941102859, United States
Santa Clara Valley Med. Ctr.
San Jose, California, 951282699, 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, 90502, United States
University of Colorado Hospital CRS
Aurora, Colorado, 80262, United States
Howard University Hosp., Div. of Infectious Diseases, ACTU
Washington D.C., District of Columbia, 20059, United States
Univ. of Miami AIDS CRS
Miami, Florida, 331361013, United States
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, 30308, United States
Queens Med. Ctr.
Honolulu, Hawaii, 96816, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, 96816, United States
Northwestern University CRS
Chicago, Illinois, 60611, United States
Cook County Hosp. CORE Ctr.
Chicago, Illinois, 60612, United States
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, 60612, United States
Weiss Memorial Hosp.
Chicago, Illinois, 60640, United States
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana, 462025250, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 46202, United States
Methodist Hosp. of Indiana
Indianapolis, Indiana, 46202, United States
Univ. of Iowa Healthcare, Div. of Infectious Diseases
Iowa City, Iowa, 52242, United States
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, 70112, United States
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, 21287, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, 02215, United States
University of Minnesota, ACTU
Minneapolis, Minnesota, 55455, United States
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, 63112, United States
Washington U CRS
St Louis, Missouri, United States
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
Omaha, Nebraska, 681985130, United States
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, 14215, United States
Beth Israel Med. Ctr., ACTU
New York, New York, 10003, United States
Cornell CRS
New York, New York, 10021, United States
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, 10029, 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, 14642, United States
Unc Aids Crs
Chapel Hill, North Carolina, 275997215, United States
Carolinas HealthCare System, Carolinas Med. Ctr.
Charlotte, North Carolina, 28203, United States
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, 27710, United States
Regional Center for Infectious Disease, Wendover Medical Center CRS
Greensboro, North Carolina, 27401, United States
Univ. of Cincinnati CRS
Cincinnati, Ohio, 452670405, United States
Case CRS
Cleveland, Ohio, 44106, United States
MetroHealth CRS
Cleveland, Ohio, 441091998, United States
The Ohio State Univ. AIDS CRS
Columbus, Ohio, 432101228, United States
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, 19104, United States
University of Washington AIDS CRS
Seattle, Washington, 981224304, United States
Puerto Rico-AIDS CRS
San Juan, 009365067, Puerto Rico
Related Publications (4)
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.
PMID: 12934177RESULTDemeter 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.
PMID: 15356820RESULTDiCenzo 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.
PMID: 14982784RESULTLok 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.
PMID: 24326304DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Margaret Fischl
- STUDY CHAIR
Ann Collier
- STUDY CHAIR
Judith Feinberg
- STUDY CHAIR
Stefano Vella