Comparison of Three Different Initial Treatments Without Protease Inhibitors for HIV Infection
- Conditions
- HIV Infections
- Registration Number
- NCT00013520
- Brief Summary
The purpose of this study is to compare the effectiveness, safety, and tolerability of 3 anti-HIV combination treatments that do not use protease inhibitors (PIs).
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.
- Detailed Description
Current treatment guidelines recommend combination regimens of 2 nucleoside analogues with either a PI or an NNRTI for the initial treatment of HIV infection. However, the efficacy of current regimens is limited by their complexity, pharmacokinetic characteristics, short- and long-term side effects, and drug-resistance profiles at the time of virologic failure. Consequently, the identification of new initial regimens that are simpler, better tolerated, preserve treatment options in the event of failure, and improve antiretroviral potency is needed. In addition, recent concern over the long-term toxicities of PIs and the extensive cross-resistance among the available PIs have led to the testing of PI-sparing regimens.
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1125
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 (60)
The Ponce de Leon Ctr. CRS
🇺🇸Atlanta, Georgia, United States
Northwestern University CRS
🇺🇸Chicago, Illinois, United States
St. Louis ConnectCare, Infectious Diseases Clinic
🇺🇸St. Louis, Missouri, United States
Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.
🇺🇸Philadelphia, Pennsylvania, United States
Pitt CRS
🇺🇸Pittsburgh, Pennsylvania, United States
Regional Center for Infectious Disease, Wendover Medical Center CRS
🇺🇸Greensboro, North Carolina, United States
HIV Prevention & Treatment CRS
🇺🇸New York, New York, United States
Cornell CRS
🇺🇸New York, New York, United States
Univ. of Rochester ACTG CRS
🇺🇸Rochester, New York, United States
Duke Univ. Med. Ctr. Adult CRS
🇺🇸Durham, North Carolina, United States
Philadelphia Veterans Admin. Med. Ctr. A6205 CRS
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt Therapeutics CRS
🇺🇸Nashville, Tennessee, United States
Unc Aids Crs
🇺🇸Chapel Hill, North Carolina, United States
The Miriam Hosp. ACTG CRS
🇺🇸Providence, Rhode Island, United States
Rhode Island Hosp.
🇺🇸Providence, Rhode Island, United States
The Ohio State Univ. AIDS CRS
🇺🇸Columbus, Ohio, United States
Hosp. of the Univ. of Pennsylvania CRS
🇺🇸Philadelphia, Pennsylvania, United States
Ucsd, Avrc Crs
🇺🇸San Diego, California, United States
Univ. of Miami AIDS CRS
🇺🇸Miami, Florida, 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
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
Univ. of Cincinnati CRS
🇺🇸Cincinnati, Ohio, United States
Case CRS
🇺🇸Cleveland, Ohio, United States
MetroHealth CRS
🇺🇸Cleveland, Ohio, United States
University of Washington AIDS CRS
🇺🇸Seattle, Washington, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
🇺🇸Honolulu, Hawaii, United States
University of Minnesota, ACTU
🇺🇸Minneapolis, Minnesota, United States
Univ. of Iowa Healthcare, Div. of Infectious Diseases
🇺🇸Iowa City, Iowa, United States
Columbia Univ., HIV Prevention and Treatment Medical Ctr.
🇺🇸New York, 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
Alabama Therapeutics CRS
🇺🇸Birmingham, Alabama, United States
USC CRS
🇺🇸Los Angeles, California, United States
Univ. of California Davis Med. Ctr., ACTU
🇺🇸Sacramento, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
UCLA CARE Center CRS
🇺🇸Los Angeles, California, United States
Stanford CRS
🇺🇸Palo Alto, California, United States
Ucsf Aids Crs
🇺🇸San Francisco, California, United States
Harbor-UCLA Med. Ctr. CRS
🇺🇸Torrance, 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
University of Colorado Hospital CRS
🇺🇸Aurora, Colorado, United States
Georgetown University CRS (GU CRS)
🇺🇸Washington, District of Columbia, United States
Rush Univ. Med. Ctr. ACTG CRS
🇺🇸Chicago, Illinois, United States
Cook County Hosp. CORE Ctr.
🇺🇸Chicago, Illinois, United States
Johns Hopkins Adult AIDS CRS
🇺🇸Baltimore, Maryland, United States
Weill Med. College of Cornell Univ., The Cornell CTU
🇺🇸New York, New York, United States
SSTAR, Family Healthcare Ctr.
🇺🇸Fall River, Massachusetts, United States
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
🇺🇸Omaha, Nebraska, United States
Beth Israel Med. Ctr., ACTU
🇺🇸New York, New York, United States
SUNY - Buffalo, Erie County Medical Ctr.
🇺🇸Buffalo, New York, United States
Washington U CRS
🇺🇸St. Louis, Missouri, United States
NY Univ. HIV/AIDS CRS
🇺🇸New York, New York, United States
Puerto Rico-AIDS CRS
🇵🇷San Juan, Puerto Rico