Home
Clinical Trials
NCT00000885

Treatment Success and Failure in HIV-Infected Subjects Receiving Indinavir in Combination With Nucleoside Analogs: A Rollover Study for ACTG 320

Last Updated: 2021-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

440 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2003-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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. \[AS PER AMENDMENT 06/29/98: Enrollment to Group B is closed to accrual. Group A patients with HIV-1 RNA of 200 copies/ml or more on 2 consecutive determinations may continue their assigned treatment or seek best alternative antiretroviral therapy, which may include access to ABC. Group B patients with plasma HIV-1 RNA of 500 copies/ml or more may continue their assigned treatment or seek best available antiretroviral therapy, which may include access to ABC, EFV, and adefovir dipivoxil with L-carnitine supplementation. Group C patients with HIV-1 RNA levels above 2,000 copies/ml and Group D patients with levels above 500 copies/ml may no longer be randomized to a treatment arm in Group B. Such patients may continue their assigned treatment or seek best available therapy, which may include access to therapy as per Group B patients.\] \[AS PER AMENDMENT 06/16/99: Study treatment for Groups B, C, and D has been completed. Group A patients with a confirmed plasma HIV-2 endpoint who remain on study may have access to ABC while on study.\] \[AS PER AMENDMENT 12/27/01: With Version 4.0 of the protocol, many of the metabolic assessments and the cardiovascular risk assessment will be repeated, and a self-reported questionnaire of body shape changes will be added. In addition, an investigation of the effect of long-term IDV on pyuria/hematuria is added, as well as a study of HIV-1 RNA in peripheral blood mononuclear cells (PBMCs).\]

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

HIV Infections

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

HIV-1 Drug Therapy, Combination Zidovudine HIV Protease Inhibitors Lamivudine Indinavir RNA, Viral Treatment Failure Reverse Transcriptase Inhibitors Anti-HIV Agents Viral Load

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Indinavir sulfate

Intervention Type DRUG

Abacavir sulfate

Intervention Type DRUG

Nelfinavir mesylate

Intervention Type DRUG

Efavirenz

Intervention Type DRUG

Levocarnitine

Intervention Type DRUG

Adefovir dipivoxil

Intervention Type DRUG

Lamivudine

Intervention Type DRUG

Stavudine

Intervention Type DRUG

Zidovudine

Intervention Type DRUG

Didanosine

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Concurrent Medication:

Required:

* Chemoprophylaxis for Pneumocystis carinii pneumonia for all patients with a CD4 cell count of 200 cells/mm3 or less.

Allowed:

* Treatment, maintenance, or chemoprophylaxis, including topical and/or oral antifungal agents unless otherwise excluded by the protocol.
* All antibiotics as clinically indicated, unless otherwise excluded in the protocol.
* Systemic corticosteroid use for 21 days or less for acute problems as medically indicated. Chronic corticosteroid use is not permitted, unless it is within physiologic replacement levels. Study team must be contacted in these instances.
* rEPO and G-CSF as medically indicated.
* Regularly prescribed medications such as \[AS PER AMENDMENT 06/29/98: alternative, FDA-approved antiretrovirals not supplied by the study\] \[AS PER AMENDMENT 12/27/01: or unapproved antiretrovirals available by expanded access (when permanently discontinued from randomized study treatment)\], antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives, megestrol acetate, testosterone, or any other medications not otherwise excluded by the protocol, as medically indicated.
* \[AS PER AMENDMENT 12/27/01: Supplemental and\] alternative therapies such as vitamins, acupuncture, and visualization techniques.

Recommended as an alternative agent for chemoprophylaxis against Mycobacterium avium complex for patients randomized to EFV in Group B or D:

* clarithromycin or azithromycin.

Patients must have:

* HIV-1 infection as documented by any licensed ELISA test kit and confirmed by either a Western Blot, HIV culture, HIV antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA at any time prior to study entry.

Non-ACTG patients:

* Documented CD4 cell count of 200 cells/mm3 or less at the time of initiation of ZDV (or d4T) plus 3TC plus IDV.
* Signed, informed consent from a parent or legal guardian for patients under 18 years of age.

Prior Medication:

Required:

Non-ACTG 320 patients:

* At least 3 months prior therapy with ZDV (or d4T) plus 3TC plus IDV and continued receipt of ZDV (or d4T) plus 3TC plus IDV until enrollment. IDV and 3TC must have been initiated concurrently.

ACTG patients:

* Randomization to the ZDV (or d4T) plus 3TC plus IDV combination arm or receipt of open-label prior to unblinding and maintenance of that treatment as participation in ACTG 320.

Group D:

* Prior NNRTI-exposure.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions and symptoms are excluded:

* Unexplained temperature above 38.5 C for any 7 days or chronic diarrhea, defined as more than 3 liquid stools per day persisting for 15 days, within 30 days prior to study treatment.
* AIDS-related malignancy, other than minimal Kaposi's sarcoma that requires systemic chemotherapy. Minimal Kaposi's sarcoma is defined as 5 or fewer cutaneous lesions and no visceral disease or tumor-associated edema that does not require systemic therapy.
* Documented or suspected acute hepatitis within 30 days prior to study entry, irrespective of laboratory values.

Concurrent Medication:

Excluded:

* All antiretroviral therapies other than study \[AS PER AMENDMENT 06/16/99: provided\] medications, \[AS PER AMENDMENT 06/16/99: unless approved by the protocol chairs\] \[AS PER AMENDMENT 12/27/01: while on original randomized treatment.\]
* Rifabutin and rifampin.
* Investigational agents without specific approval from the protocol chair.
* Systemic cytotoxic chemotherapy.
* Oral ketoconazole and itraconazole. NOTE: Itraconazole may be permitted for Group B and Group D patients if fluconazole is not an option.
* Terfenadine, astemizole, cisapride, triazolam, midazolam, amiodarone, quinine, ergot derivatives, isotretinoin, \[AS PER AMENDMENT 12/27/01: pimozide, St.John's Wort, and milk thistle.\]
* \[AS PER AMENDMENT 12/27/01: Concomitant use of lovastatin or simvastatin is not recommended because of potential drug interactions. Pravastatin or atorvastatin may be used after consultation with the Study Team.\]

To be avoided:

* Herbal medications.

Prior Medication:

Excluded:

* Any prior protease inhibitor therapy other than indinavir.
* Interferons, interleukins, or HIV vaccines within 30 days prior to study entry.
* Any experimental therapy within 30 days prior to study entry.
* Rifampin, rifabutin, ketoconazole, or itraconazole within 14 days of study entry.

Non-ACTG patients:

* Acute therapy for an infection or other medical illness within 14 days prior to study therapy.
* NNRTI therapy prior to study entry (with the exception of Group D).
* Recombinant erythropoietin (rEPO), granulocyte colony-stimulating factor (G-CSF, filgrastim), or granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim) within 30 days prior to study entry.

Caution should be taken in the consumption of alcoholic beverages with study medications.

Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Scott Hammer

Role: STUDY_CHAIR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Univ of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Univ of Southern California / LA County USC Med Ctr

Los Angeles, California, United States

Site Status

Stanford at Kaiser / Kaiser Permanente Med Ctr

San Francisco, California, United States

Site Status

Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium

San Jose, California, United States

Site Status

San Mateo AIDS Program / Stanford Univ

Stanford, California, United States

Site Status

Stanford Univ Med Ctr

Stanford, California, United States

Site Status

Harbor UCLA Med Ctr

Torrance, California, United States

Site Status

Univ of Colorado Health Sciences Ctr

Denver, Colorado, United States

Site Status

Georgetown Univ Hosp

Washington D.C., District of Columbia, United States

Site Status

Howard Univ

Washington D.C., District of Columbia, United States

Site Status

Univ of Miami School of Medicine

Miami, Florida, United States

Site Status

Emory Univ

Atlanta, Georgia, United States

Site Status

Queens Med Ctr

Honolulu, Hawaii, United States

Site Status

Univ of Hawaii

Honolulu, Hawaii, United States

Site Status

Northwestern Univ Med School

Chicago, Illinois, United States

Site Status

Cook County Hosp

Chicago, Illinois, United States

Site Status

Rush Presbyterian - Saint Luke's Med Ctr

Chicago, Illinois, United States

Site Status

Louis A Weiss Memorial Hosp

Chicago, Illinois, United States

Site Status

Indiana Univ Hosp

Indianapolis, Indiana, United States

Site Status

Division of Inf Diseases/ Indiana Univ Hosp

Indianapolis, Indiana, United States

Site Status

Methodist Hosp of Indiana / Life Care Clinic

Indianapolis, Indiana, United States

Site Status

Univ of Iowa Hosp and Clinic

Iowa City, Iowa, United States

Site Status

Tulane Univ School of Medicine

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Hosp

Baltimore, Maryland, United States

Site Status

Harvard (Massachusetts Gen Hosp)

Boston, Massachusetts, United States

Site Status

Boston Med Ctr

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess - West Campus

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Med Ctr

Boston, Massachusetts, United States

Site Status

Univ of Minnesota

Minneapolis, Minnesota, United States

Site Status

St Louis Regional Hosp / St Louis Regional Med Ctr

St Louis, Missouri, United States

Site Status

Univ of Nebraska Med Ctr

Omaha, Nebraska, United States

Site Status