Addition of Efavirenz or Nelfinavir to a Lamivudine/Zidovudine/Indinavir HIV Treatment Regimen
- Conditions
- HIV Infections
- Registration Number
- NCT00000903
- 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.
- Detailed Description
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.
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. \[AS PER AMENDMENT 4/3/00: Optimally, Step 2 treatment regimens should contain 3 or 4 drugs to which the virus is susceptible. If this is not possible, a drug to which the virus is partially susceptible is acceptable, but a drug to which the virus is resistant should not be included.\]
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 444
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (50)
USC CRS
🇺🇸Los Angeles, California, United States
UCLA CARE Center CRS
🇺🇸Los Angeles, California, United States
Marin County Dept. of Health & Human Services, HIV/AIDS Program & Specialty Clinic
🇺🇸San Rafael, California, United States
Rush Univ. Med. Ctr. ACTG CRS
🇺🇸Chicago, Illinois, United States
Regional Center for Infectious Disease, Wendover Medical Center CRS
🇺🇸Greensboro, North Carolina, United States
Univ. of Miami AIDS CRS
🇺🇸Miami, Florida, United States
MetroHealth CRS
🇺🇸Cleveland, Ohio, 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
Univ. of Cincinnati CRS
🇺🇸Cincinnati, Ohio, United States
University of Washington AIDS CRS
🇺🇸Seattle, Washington, United States
Ucsf Aids Crs
🇺🇸San Francisco, California, United States
Case CRS
🇺🇸Cleveland, Ohio, United States
Univ. of Rochester ACTG CRS
🇺🇸Rochester, New York, United States
Ucsd, Avrc Crs
🇺🇸San Diego, California, United States
Alabama Therapeutics CRS
🇺🇸Birmingham, Alabama, United States
Santa Clara Valley Med. Ctr.
🇺🇸San Jose, California, United States
Harbor-UCLA Med. Ctr. CRS
🇺🇸Torrance, California, United States
Stanford CRS
🇺🇸Palo Alto, California, United States
University of Colorado Hospital CRS
🇺🇸Aurora, Colorado, United States
Queens Med. Ctr.
🇺🇸Honolulu, Hawaii, United States
The Ponce de Leon Ctr. CRS
🇺🇸Atlanta, Georgia, United States
Weiss Memorial Hosp.
🇺🇸Chicago, Illinois, 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
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
🇺🇸New Orleans, Louisiana, United States
University of Minnesota, ACTU
🇺🇸Minneapolis, Minnesota, United States
Washington U CRS
🇺🇸St. Louis, Missouri, United States
St. Louis ConnectCare, Infectious Diseases Clinic
🇺🇸St Louis, Missouri, United States
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
🇺🇸Omaha, Nebraska, United States
Beth Israel Med. Ctr. (Mt. Sinai)
🇺🇸New York, New York, United States
Beth Israel Med. Ctr., ACTU
🇺🇸New York, New York, United States
Cornell CRS
🇺🇸New York, New York, United States
Cornell University A2201
🇺🇸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
Unc Aids Crs
🇺🇸Chapel Hill, North Carolina, United States
Duke Univ. Med. Ctr. Adult CRS
🇺🇸Durham, North Carolina, United States
Carolinas HealthCare System, Carolinas Med. Ctr.
🇺🇸Charlotte, North Carolina, United States
The Ohio State Univ. AIDS CRS
🇺🇸Columbus, Ohio, United States
Hosp. of the Univ. of Pennsylvania CRS
🇺🇸Philadelphia, Pennsylvania, United States
Puerto Rico-AIDS CRS
🇵🇷San Juan, Puerto Rico
SUNY - Buffalo, Erie County Medical Ctr.
🇺🇸Buffalo, New York, United States
Northwestern University CRS
🇺🇸Chicago, Illinois, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
🇺🇸Boston, Massachusetts, United States
Cook County Hosp. CORE Ctr.
🇺🇸Chicago, Illinois, United States
San Mateo County AIDS Program
🇺🇸San Mateo, California, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
🇺🇸Honolulu, Hawaii, United States
Howard University Hosp., Div. of Infectious Diseases, ACTU
🇺🇸Washington, District of Columbia, United States