Treatment Success and Failure in HIV-Infected Subjects Receiving Indinavir in Combination With Nucleoside Analogs: A Rollover Study for ACTG 320
- Conditions
- HIV Infections
- Registration Number
- NCT00000885
- Brief Summary
Group A:
To compare the time to confirmed virologic failure (2 consecutive plasma HIV-RNA concentrations of 500 copies/ml or more) between the treatment arms: abacavir (ABC) or placebo in combination with zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV). To evaluate the safety and tolerability of these treatment arms. \[AS PER AMENDMENT 06/16/99: To compare the time to confirmed treatment failure, permanent discontinuation of treatment, or death between the treatment arms.\] \[AS PER AMENDMENT 12/27/01: Groups B, C, and D completed follow-up on March 4, 1999. Therefore, only information pertinent to Group A is applicable.\]
Group B:
To compare the proportion of patients who achieve plasma HIV-1 RNA concentrations below 500 copies/ml, as assessed by the standard Roche Amplicor assay at Week 16, or to compare the absolute changes in plasma HIV-1 RNA concentrations at Week 16 across the treatment arms: ABC or approved nucleoside analogs and nelfinavir (NFV) or placebo in combination with efavirenz (EFV) and adefovir dipivoxil. To compare the safety and tolerability of these treatment arms.
Group C:
To monitor plasma HIV-1 RNA trajectory over time and determine the time to a confirmed plasma HIV-1 RNA concentration above 2,000 copies/ml on 2 consecutive determinations for patients treated with ZDV or stavudine (d4T) plus 3TC and IDV.
Group D:
To evaluate plasma HIV-1 RNA responses at Weeks 16 and 48. To evaluate the safety and tolerability of the treatment arms: ABC, EFV, adefovir dipivoxil, and NFV.
This study explores new treatment options for ACTG 320 enrollees (and, if needed, a limited number of non-ACTG 320 volunteers) who have been receiving ZDV (or d4T) plus 3TC and IDV and are currently exhibiting a range of virologic responses. By dividing the study into the corresponding, nonsequential cohorts (Groups A, B, C, D), different approaches to evaluating virologic success, i.e., undetectable plasma HIV-1 RNA levels, and virologic failure, i.e., plasma HIV-1 RNA levels of 500 copies/ml or more \[AS PER AMENDMENT 12/27/01: 200 copies/ml or more\], are explored while maintaining long-term follow-up of ACTG 320 patients. \[AS PER AMENDMENT 12/27/01: Groups B, C, and D completed follow-up on March 4, 1999. Therefore, only information pertinent to Group A is applicable. This study will examine the question of whether intensification of therapy can prolong the virologic benefit in individuals whose plasma HIV-1 RNA concentrations have been below the limits of assay detection on ZDV (or d4T) plus 3TC plus IDV.\]
- Detailed Description
This study explores new treatment options for ACTG 320 enrollees (and, if needed, a limited number of non-ACTG 320 volunteers) who have been receiving ZDV (or d4T) plus 3TC and IDV and are currently exhibiting a range of virologic responses. By dividing the study into the corresponding, nonsequential cohorts (Groups A, B, C, D), different approaches to evaluating virologic success, i.e., undetectable plasma HIV-1 RNA levels, and virologic failure, i.e., plasma HIV-1 RNA levels of 500 copies/ml or more \[AS PER AMENDMENT 12/27/01: 200 copies/ml or more\], are explored while maintaining long-term follow-up of ACTG 320 patients. \[AS PER AMENDMENT 12/27/01: Groups B, C, and D completed follow-up on March 4, 1999. Therefore, only information pertinent to Group A is included. This study will examine the question of whether intensification of therapy can prolong the virologic benefit in individuals whose plasma HIV-1 RNA concentrations have been below the limits of assay detection on ZDV (or d4T) plus 3TC plus IDV.\]
Rollover patients from ACTG 320 are given enrollment priority and permitted to enroll in all 4 study groups; non-ACTG patients are permitted to enroll in Groups A and B if accrual objectives are not met with ACTG 320 patients.
GROUP A:
Patients with screening plasma HIV-1 RNA concentrations below 500 copies/ml are randomized to 1 of 2 treatment arms and stratified according to their participation in ACTG 320 (original randomization to IDV versus open-label IDV). The 2 treatment arms are as follows:
ARM A1: IDV plus ZDV (or d4T) plus 3TC plus ABC. ARM A2: IDV plus ZDV (or d4T) plus 3TC plus ABC placebo. Patients who achieve a plasma HIV-1 RNA level of 500 copies/ml or more on 2 consecutive determinations may continue their assigned arm in a blinded fashion, or seek the best alternative therapy selected by the local investigator or primary care physician.
GROUP B:
Nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients with plasma HIV-1 RNA plasma concentrations of 500 copies/ml or more are randomized to 1 of 4 treatment arms and stratified by plasma HIV-1 RNA concentrations (above versus below 15,000 RNA copies/ml) and participation in ACTG 320 (original randomization to IDV versus open-label IDV). The treatment arms are as follows:
ARM B1: ABC plus EFV plus adefovir dipivoxil plus NFV. ARM B2: ABC plus EFV plus adefovir dipivoxil plus NFV placebo. ARM B3: 2 nucleoside reverse transcriptase inhibitors (NRTIs) (or 1 if 2 not tolerated) (chosen from ZDV, 3TC, d4T, or didanosine \[ddI\]) plus EFV plus adefovir dipivoxil plus NFV.
ARM B4: 2 NRTIs (or 1 if 2 not tolerated) (chosen from ZDV, 3TC, d4T, or ddI) plus EFV plus adefovir dipivoxil plus NFV placebo.
GROUP C:
NNRTI-naive patients with plasma HIV-1 RNA concentrations of 500-2,000 copies/ml at screening may elect to be randomized to a treatment arm in Group B or continue with their current ACTG 320 regimen as follows:
ARM C: ZDV (or d4T) plus 3TC plus IDV. Patients who elect this treatment are randomized in Group B if their plasma HIV-1 RNA concentrations are confirmed to be above 2,000 copies.
GROUP D:
NNRTI-experienced, ACTG 320 patients with screening plasma HIV-1 RNA concentrations of 500 copies/ml or more receive open-label treatment as follows:
ARM D: ABC plus EFV plus adefovir dipivoxil plus NFV. \[AS PER AMENDMENT 06/29/98: Enrollment to Group B is closed to accrual. Group A patients with HIV-1 RNA of 200 copies/ml or more on 2 consecutive determinations may continue their assigned treatment or seek best alternative antiretroviral therapy, which may include access to ABC. Group B patients with plasma HIV-1 RNA of 500 copies/ml or more may continue their assigned treatment or seek best available antiretroviral therapy, which may include access to ABC, EFV, and adefovir dipivoxil with L-carnitine supplementation. Group C patients with HIV-1 RNA levels above 2,000 copies/ml and Group D patients with levels above 500 copies/ml may no longer be randomized to a treatment arm in Group B. Such patients may continue their assigned treatment or seek best available therapy, which may include access to therapy as per Group B patients.\] \[AS PER AMENDMENT 06/16/99: Study treatment for Groups B, C, and D has been completed. Group A patients with a confirmed plasma HIV-2 endpoint who remain on study may have access to ABC while on study.\] \[AS PER AMENDMENT 12/27/01: With Version 4.0 of the protocol, many of the metabolic assessments and the cardiovascular risk assessment will be repeated, and a self-reported questionnaire of body shape changes will be added. In addition, an investigation of the effect of long-term IDV on pyuria/hematuria is added, as well as a study of HIV-1 RNA in peripheral blood mononuclear cells (PBMCs).\]
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 440
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 (53)
Univ of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Univ of Southern California / LA County USC Med Ctr
🇺🇸Los Angeles, California, United States
Stanford at Kaiser / Kaiser Permanente Med Ctr
🇺🇸San Francisco, California, United States
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
🇺🇸San Jose, California, United States
San Mateo AIDS Program / Stanford Univ
🇺🇸Stanford, California, United States
Stanford Univ Med Ctr
🇺🇸Stanford, California, United States
Harbor UCLA Med Ctr
🇺🇸Torrance, California, United States
Univ of Colorado Health Sciences Ctr
🇺🇸Denver, Colorado, United States
Georgetown Univ Hosp
🇺🇸Washington, District of Columbia, United States
Howard Univ
🇺🇸Washington, District of Columbia, United States
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