A Study of Three Treatment Combinations Using Zidovudine Plus Lamivudine Plus Indinavir in HIV-Infected Patients
- Conditions
- HIV Infections
- Registration Number
- NCT00001084
- Brief Summary
To compare the proportion of patients who sustain suppression of plasma HIV RNA to undetectable levels \[AS PER AMENDMENT 09/19/97: below 200 copies/mL by Roche UltraSensitive assay\] among the 3 regimens during the maintenance phase.
The objective of antiretroviral therapy is to reduce HIV replication, preserve immunologic function and delay the development of HIV-related complications. In patients administered potent antiretroviral regimens, HIV RNA levels are reduced below 500 copies/ml of plasma and below the level of detection of commercially available assays. This protocol attempts to learn if a less intensive regimen can successfully sustain viral suppression after induction with a triple-drug regimen. The study also addresses whether HIV can be eradicated in patients following prolonged treatment with induction and maintenance regimens.
- Detailed Description
The objective of antiretroviral therapy is to reduce HIV replication, preserve immunologic function and delay the development of HIV-related complications. In patients administered potent antiretroviral regimens, HIV RNA levels are reduced below 500 copies/ml of plasma and below the level of detection of commercially available assays. This protocol attempts to learn if a less intensive regimen can successfully sustain viral suppression after induction with a triple-drug regimen. The study also addresses whether HIV can be eradicated in patients following prolonged treatment with induction and maintenance regimens.
All patients will receive open label induction therapy with zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV) for 6 months. Following the 6 month induction phase, patients with undetectable plasma HIV RNA at weeks 16, 20 and 24 will enter the maintenance phase \[blinded maintenance phase AS PER AMENDMENT 09/19/97\] and be randomized to one of three maintenance regimens, i.e., either continued ZDV/3TC/IDV (control), or ZDV/3TC/IDV placebo or ZDV placebo/3TC placebo/IDV. Prior to randomization, patients are stratified according to entry HIV RNA level (greater than or equal to 30,000 or less than 30,000 copies/ml) and by prior ZDV therapy (at least 7 days or less than 7 days). After 12 months \[AS PER AMENDMENT 09/19/97: 18 months\] of maintenance therapy, treatment will be withdrawn at 6-month intervals in randomly-selected patients who have achieved undetectable HIV RNA. AS PER 09/19/97 AMENDMENT: After 18 months of blinded maintenance therapy, treatment is unblinded for patients whose HIV RNA levels remain detectable. Such patients receive optimal therapy, either continuing the protocol regimen or initiating alternative therapy.
AS PER AMENDMENT 2/27/98: An interim review conducted in January, 1998 demonstrated that the strategy of less intensive antiviral therapy after 6 months of IDV/3TC/ZDV induction therapy is less effective than continuation of triple drug therapy except for ZDV-naive patients assigned to ZDV/3TC. Therefore, the maintenance phase of this study has been discontinued.
Patients currently on blinded maintenance are unblinded immediately and have the option of reinitiating open-label triple therapy with IDV/3TC/ZDV or discontinuing study treatment. Patients currently on induction may register for continued open-label triple therapy or may discontinue study treatment. This amendment allows treatment extension so that subjects may receive open-label triple therapy until May 31, 1998. At that time, a rollover protocol or another modification with a longer period of drug supply may become available. Patients who choose to go off treatment are followed until May 31, 1998.
AS PER AMENDMENT 04/23/98: This study will now provide treatment with open-label ZDV/3TC/IDV until August 1, 1998. A rollover protocol or another 343 protocol modification with a longer period of drug supply may become available, but this cannot be guaranteed.
AS PER AMENDMENT 06/19/98: This study will now provide treatment with open-label ZDV/3TC/IDV until either November 1, 1998 or until 3 months after the rollover study (A5025) is available to the study sites (whichever comes first).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 500
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 (45)
Univ of Southern California / LA County USC Med Ctr
🇺🇸Los Angeles, California, United States
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
🇺🇸San Jose, California, United States
Stanford Univ Med Ctr
🇺🇸Stanford, California, United States
Harbor UCLA Med Ctr
🇺🇸Torrance, California, United States
Emory Univ
🇺🇸Atlanta, Georgia, United States
Univ of Hawaii
🇺🇸Honolulu, Hawaii, United States
Univ of Iowa Hosp and Clinic
🇺🇸Iowa City, Iowa, United States
State of MD Div of Corrections / Johns Hopkins Univ Hosp
🇺🇸Baltimore, Maryland, United States
Johns Hopkins Hosp
🇺🇸Baltimore, Maryland, United States
St Paul Ramsey Med Ctr
🇺🇸Saint Paul, Minnesota, United States
St Louis Regional Hosp / St Louis Regional Med Ctr
🇺🇸Saint Louis, Missouri, United States
Beth Israel Med 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
Mount Sinai Med Ctr
🇺🇸New York, New York, United States
Mem Sloan - Kettering Cancer Ctr
🇺🇸New York, New York, United States
Univ of Rochester Medical Center
🇺🇸Rochester, New York, United States
Moses H Cone Memorial Hosp
🇺🇸Greensboro, North Carolina, United States
Carolinas Med Ctr
🇺🇸Charlotte, North Carolina, United States
Univ of Texas Galveston
🇺🇸Galveston, Texas, United States
Julio Arroyo
🇺🇸West Columbia, South Carolina, United States
Univ of California / San Diego Treatment Ctr
🇺🇸San Diego, California, United States
Univ of Miami School of Medicine
🇺🇸Miami, Florida, United States
Cook County Hosp
🇺🇸Chicago, Illinois, United States
Beth Israel Deaconess - West Campus
🇺🇸Boston, Massachusetts, United States
Northwestern Univ Med School
🇺🇸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
Case Western Reserve Univ
🇺🇸Cleveland, Ohio, United States
MetroHealth Med Ctr
🇺🇸Cleveland, Ohio, United States
Ohio State Univ Hosp Clinic
🇺🇸Columbus, Ohio, United States
Univ of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Univ of Washington
🇺🇸Seattle, Washington, United States
Queens Med Ctr
🇺🇸Honolulu, Hawaii, United States
Stanford at Kaiser / Kaiser Permanente Med Ctr
🇺🇸San Francisco, California, United States
San Francisco Gen Hosp
🇺🇸San Francisco, California, United States
Univ of Colorado Health Sciences Ctr
🇺🇸Denver, Colorado, United States
Tulane Med Ctr Hosp
🇺🇸New Orleans, Louisiana, United States
Tulane Univ School of Medicine
🇺🇸New Orleans, Louisiana, United States
Hennepin County Med Clinic
🇺🇸Minneapolis, Minnesota, United States
Univ of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Univ of Nebraska Med Ctr
🇺🇸Omaha, Nebraska, United States
Univ of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
San Mateo AIDS Program / Stanford Univ
🇺🇸Stanford, California, United States