A Study of Abacavir Plus Indinavir Sulfate Plus Efavirenz in HIV-Infected Patients
- Conditions
- HIV Infections
- Registration Number
- NCT00001086
- Brief Summary
To compare the virologic response between abacavir (ABC, 1592U89) regimens (drug vs. placebo) and between the 2 dosing regimens (BID vs. TID) with respect to the proportion of patients with plasma HIV RNA levels below the limit of detection \[AS PER AMENDMENT 8/27/97: \< 500 copies/ml at week 16\]. To evaluate the safety and tolerance of the study arms. \[AS PER AMENDMENT 3/10/99: During the extension period, compare the time to detectable viremia (2 consecutive plasma HIV RNA levels greater than or equal to 500 copies/ml) between ABC and placebo.\] Therapeutically, there is a need to explore potent alternative therapy for patients who have received, or are currently receiving, a double nucleoside analog combination including lamivudine (3TC), a regimen that was proven to be clinically inferior to indinavir (IDV) when combined with zidovudine/3TC in study ACTG 320. In order to produce and maintain a maximal antiviral response, all patients in this study will receive 2 or 3 potent, new agents; ABC, a nucleoside analog, EFV, a non-nucleoside reverse transcriptase inhibitor (NNRTI), and IDV, a protease inhibitor. Virologically, the major question this protocol seeks to answer is how prior 3TC exposure in a dual nucleoside regimen influences the response to subsequent treatment. It is unclear whether it is best to add a protease inhibitor either 1) an NNRTI at 1 of 2 doses, or 2) an NNRTI at 1 of 2 doses plus a new nucleoside analog to achieve plasma HIV RNA levels that are below the limits of detection.
- Detailed Description
Therapeutically, there is a need to explore potent alternative therapy for patients who have received, or are currently receiving, a double nucleoside analog combination including lamivudine (3TC), a regimen that was proven to be clinically inferior to indinavir (IDV) when combined with zidovudine/3TC in study ACTG 320. In order to produce and maintain a maximal antiviral response, all patients in this study will receive 2 or 3 potent, new agents; ABC, a nucleoside analog, EFV, a non-nucleoside reverse transcriptase inhibitor (NNRTI), and IDV, a protease inhibitor. Virologically, the major question this protocol seeks to answer is how prior 3TC exposure in a dual nucleoside regimen influences the response to subsequent treatment. It is unclear whether it is best to add a protease inhibitor either 1) an NNRTI at 1 of 2 doses, or 2) an NNRTI at 1 of 2 doses plus a new nucleoside analog to achieve plasma HIV RNA levels that are below the limits of detection.
Prior to randomization, patients are stratified by CD4 cell count (cells/mm3): less than or equal to 50 versus greater than 50 and by ACTG 320 participation: enrolled versus not enrolled. Patients with greater than 50 CD4 cells/mm3 are randomized to 1 of 4 treatment arms (Arms I, II, III, or IV) and patients with less than or equal to 50 CD4 cells/mm3 are randomized to 1 of 2 treatment arms (Arms I and II). All patients will be followed for 48 weeks beyond the enrollment of the last patient. The regimens for the treatment arms are as follows: Arm I - indinavir (IDV) plus EFV plus ABC placebo bid, Arm II - IDV (higher dose) plus EFV (lower dose) plus ABC, Arm III - IDV plus EFV plus ABC placebo, and Arm IV - IDV (higher dose) plus EFV (lower dose) plus ABC. If 15 week data indicates this is a reasonable dosing regimen, the sample size in Arms III and IV will be expanded to include additional patients with a CD4 count greater than 50 cells/mm3 and allow for equal enrollment across all 4 treatment arms. Those patients who roll over from ACTG 320 will be assigned to receive open-label treatment on Arm II and evaluated independently of the 4 treatment arms listed above.
\[AS PER AMENDMENT 8/27/97: Patients with 2 consecutive HIV RNA measurements at least 500 copies/ml at week 16 or anytime thereafter are given the option to receive open-label treatment with IDV plus EFV plus ABC, or to seek the best available therapy outside of the study. NOTE: Patients who choose the open-label combination may take other prescribed nucleoside analogs provided outside the study.\] \[AS PER AMENDMENT 12/17/97: It is strongly recommended that patients who reach a confirmed endpoint and elect to receive open-label therapy consider adding additional approved (and novel, if possible) antiretroviral agents to their open-label regimen.\] \[AS PER AMENDMENT 1/12/98: Patients who choose the open-label combination may receive other approved antiretrovirals obtained outside the study provided the ACTG 368 team approves the combination.\] \[AS PER AMENDMENT 8/7/98: Subjects will take study medications for a maximum of 96 weeks, depending on their time of study enrollment.\] \[AS PER AMENDMENT 3/10/99: A 24-week extension, which will end July 30, 1999, has been added to the study. The extension applies to subjects currently on blinded Step 1 treatment, on open-labeled Step 2, or on study but off treatment. Subjects are to be unblinded in their study treatment and followed for the remainder of the extension. Subjects continue on their current study drug schedule. Subjects on blinded IDV plus EFV who, upon unblinding (not failure) decide to add prescription ABC to their regimen, will be considered off study treatment and will be followed for the duration of the extension; those already registered on Step 2 will continue their Step 2 therapy. Any subject who does not wish to continue on the study extension will be unblinded to their original randomized regimen. Subjects who experience virologic failure during the extension should seek best available treatment following current recommendations to use as many approved, novel antiretroviral agents as possible. The new drug regimen may incorporate any or all of the study drugs.\]
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 300
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 (56)
Johns Hopkins Hosp
🇺🇸Baltimore, Maryland, United States
Stanford Univ Med Ctr
🇺🇸Stanford, California, United States
Stanford at Kaiser / Kaiser Permanente Med Ctr
🇺🇸San Francisco, California, United States
Georgetown Univ Hosp
🇺🇸Washington, District of Columbia, United States
Univ of Colorado Health Sciences Ctr
🇺🇸Denver, Colorado, United States
Howard Univ
🇺🇸Washington, District of Columbia, United States
Queens Med Ctr
🇺🇸Honolulu, Hawaii, United States
UCLA CARE Ctr
🇺🇸Los Angeles, California, United States
Univ of Southern California / LA County USC Med Ctr
🇺🇸Los Angeles, California, United States
San Francisco Gen Hosp
🇺🇸San Francisco, California, United States
Univ of Hawaii
🇺🇸Honolulu, Hawaii, United States
Univ of Iowa Hosp and Clinic
🇺🇸Iowa City, Iowa, United States
Tulane Univ School of Medicine
🇺🇸New Orleans, Louisiana, United States
Moses H Cone Memorial Hosp
🇺🇸Greensboro, North Carolina, United States
Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
🇺🇸Knoxville, Tennessee, United States
Univ of Pennsylvania at Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Univ of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Milton S Hershey Med Ctr
🇺🇸Hershey, Pennsylvania, United States
Univ of Puerto Rico
🇵🇷San Juan, Puerto Rico
Univ of Miami School of Medicine
🇺🇸Miami, Florida, United States
Northwestern Univ Med School
🇺🇸Chicago, Illinois, United States
Rush Presbyterian - Saint Luke's Med Ctr
🇺🇸Chicago, Illinois, United States
Louis A Weiss Memorial Hosp
🇺🇸Chicago, Illinois, United States
Indiana Univ Hosp
🇺🇸Indianapolis, Indiana, United States
Division of Inf Diseases/ Indiana Univ Hosp
🇺🇸Indianapolis, Indiana, United States
Harvard (Massachusetts Gen Hosp)
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess - West Campus
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Med Ctr
🇺🇸Boston, Massachusetts, United States
Case Western Reserve Univ
🇺🇸Cleveland, Ohio, United States
Ohio State Univ Hosp Clinic
🇺🇸Columbus, Ohio, United States
Univ of Washington
🇺🇸Seattle, Washington, United States
State of MD Div of Corrections / Johns Hopkins Univ Hosp
🇺🇸Baltimore, Maryland, United States
St Louis Regional Hosp / St Louis Regional Med Ctr
🇺🇸Saint Louis, Missouri, United States
St Paul Ramsey Med Ctr
🇺🇸Saint Paul, Minnesota, United States
Central Prison/Women's Prison in Raleigh / NC
🇺🇸Raleigh, North Carolina, United States
Charity Hosp / Tulane Univ Med School
🇺🇸New Orleans, Louisiana, United States
Tulane Med Ctr Hosp
🇺🇸New Orleans, Louisiana, United States
Boston Med Ctr
🇺🇸Boston, Massachusetts, United States
Univ of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Hennepin County Med Clinic
🇺🇸Minneapolis, Minnesota, United States
SUNY / Erie County Med Ctr at Buffalo
🇺🇸Buffalo, New York, United States
Univ of Nebraska Med Ctr
🇺🇸Omaha, Nebraska, United States
St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr
🇺🇸New York, New York, United States
Bellevue Hosp / New York Univ Med Ctr
🇺🇸New York, New York, United States
Saint Clare's Hosp and Health Ctr
🇺🇸New York, New York, United States
Beth Israel Med Ctr
🇺🇸New York, New York, United States
Cornell Univ Med Ctr
🇺🇸New York, New York, United States
Mount Sinai Med Ctr
🇺🇸New York, New York, United States
Univ of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Duke Univ Med Ctr
🇺🇸Durham, North Carolina, United States
Univ of Rochester Medical Center
🇺🇸Rochester, New York, United States
Univ of Kentucky Lexington
🇺🇸Cincinnati, Ohio, United States
Univ of Texas Galveston
🇺🇸Galveston, Texas, United States
Julio Arroyo
🇺🇸West Columbia, South Carolina, United States
Vanderbilt Univ Med Ctr
🇺🇸Nashville, Tennessee, United States
Great Lakes Hemophilia Foundation
🇺🇸Wauwatosa, Wisconsin, United States