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. \[AS PER AMENDMENT 12/27/01: Groups B, C, and D completed follow-up on March 4, 1999. Therefore, only information pertinent to Group A is applicable. This study will examine the question of whether intensification of therapy can prolong the virologic benefit in individuals whose plasma HIV-1 RNA concentrations have been below the limits of assay detection on ZDV (or d4T) plus 3TC plus IDV.\]

Trial Health

85
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
440

participants targeted

Target at P75+ for phase_2 hiv-infections

Geographic Reach
2 countries

53 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 2, 1999

Completed
1.8 years until next milestone

First Posted

Study publicly available on registry

August 31, 2001

Completed
1.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2003

Completed
Last Updated

October 28, 2021

Status Verified

October 1, 2021

First QC Date

November 2, 1999

Last Update Submit

October 27, 2021

Conditions

Keywords

HIV-1Drug Therapy, CombinationZidovudineHIV Protease InhibitorsLamivudineIndinavirRNA, ViralTreatment FailureReverse Transcriptase InhibitorsAnti-HIV AgentsViral Load

Interventions

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • +10 more criteria

You may not qualify if:

  • 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:
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (53)

Univ of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Univ of Southern California / LA County USC Med Ctr

Los Angeles, California, 900331079, United States

Location

Stanford at Kaiser / Kaiser Permanente Med Ctr

San Francisco, California, 94115, United States

Location

Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium

San Jose, California, 951282699, United States

Location

San Mateo AIDS Program / Stanford Univ

Stanford, California, 943055107, United States

Location

Stanford Univ Med Ctr

Stanford, California, 943055107, United States

Location

Harbor UCLA Med Ctr

Torrance, California, 90502, United States

Location

Univ of Colorado Health Sciences Ctr

Denver, Colorado, 80262, United States

Location

Georgetown Univ Hosp

Washington D.C., District of Columbia, 20037, United States

Location

Howard Univ

Washington D.C., District of Columbia, 20059, United States

Location

Univ of Miami School of Medicine

Miami, Florida, 331361013, United States

Location

Emory Univ

Atlanta, Georgia, 30308, United States

Location

Queens Med Ctr

Honolulu, Hawaii, 96816, United States

Location

Univ of Hawaii

Honolulu, Hawaii, 96816, United States

Location

Northwestern Univ Med School

Chicago, Illinois, 60611, United States

Location

Cook County Hosp

Chicago, Illinois, 60612, United States

Location

Rush Presbyterian - Saint Luke's Med Ctr

Chicago, Illinois, 60612, United States

Location

Louis A Weiss Memorial Hosp

Chicago, Illinois, 60640, United States

Location

Indiana Univ Hosp

Indianapolis, Indiana, 462025250, United States

Location

Division of Inf Diseases/ Indiana Univ Hosp

Indianapolis, Indiana, 46202, United States

Location

Methodist Hosp of Indiana / Life Care Clinic

Indianapolis, Indiana, 46202, United States

Location

Univ of Iowa Hosp and Clinic

Iowa City, Iowa, 52242, United States

Location

Tulane Univ School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins Hosp

Baltimore, Maryland, 21287, United States

Location

Harvard (Massachusetts Gen Hosp)

Boston, Massachusetts, 02114, United States

Location

Boston Med Ctr

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess - West Campus

Boston, Massachusetts, 02215, United States

Location

Beth Israel Deaconess Med Ctr

Boston, Massachusetts, 02215, United States

Location

Univ of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

St Louis Regional Hosp / St Louis Regional Med Ctr

St Louis, Missouri, 63112, United States

Location

Univ of Nebraska Med Ctr

Omaha, Nebraska, 681985130, United States

Location

SUNY / Erie County Med Ctr at Buffalo

Buffalo, New York, 14215, United States

Location

Beth Israel Med Ctr

New York, New York, 10003, United States

Location

Bellevue Hosp / New York Univ Med Ctr

New York, New York, 10016, United States

Location

Chelsea Ctr

New York, New York, 10021, United States

Location

Cornell Univ Med Ctr

New York, New York, 10021, United States

Location

St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr

New York, New York, 10021, United States

Location

Mount Sinai Med Ctr

New York, New York, 10029, United States

Location

Univ of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Univ of North Carolina

Chapel Hill, North Carolina, 275997215, United States

Location

Carolinas Med Ctr

Charlotte, North Carolina, 28203, United States

Location

Duke Univ Med Ctr

Durham, North Carolina, 27710, United States

Location

Moses H Cone Memorial Hosp

Greensboro, North Carolina, 27401, United States

Location

Univ of Cincinnati

Cincinnati, Ohio, 452670405, United States

Location

Univ of Kentucky Lexington

Cincinnati, Ohio, 45267, United States

Location

MetroHealth Med Ctr

Cleveland, Ohio, 441091998, United States

Location

Ohio State Univ Hosp Clinic

Columbus, Ohio, 432101228, United States

Location

Julio Arroyo

West Columbia, South Carolina, 29169, United States

Location

Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr

Knoxville, Tennessee, 37920, United States

Location

Vanderbilt Univ Med Ctr

Nashville, Tennessee, 37203, United States

Location

Univ of Texas Galveston

Galveston, Texas, 775550435, United States

Location

Univ Texas Health Science Ctr / Univ Texas Med School

Houston, Texas, 77030, United States

Location

Univ of Puerto Rico

San Juan, 009365067, Puerto Rico

Location

Related Publications (4)

  • Henry K, Zackin R, Dube M, Hammer S, Currier J. ACTG 5056: metabolic status and cardiovascular disease risk for a cohort of HIV-1-infected persons durably suppressed on an indinavir-containing regimen (ACTG 372A). 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 656)

    BACKGROUND
  • Hammer S, Squires K, Degruttola V, Fischl M, Bassett R, Demeter L, Hertogs K, Larder B. Randomized trial of abacavir (ABC) & nelfinavir (NFV) in combination with efavirenz (EFV) & adefovir dipivoxil (ADV) as salvage therapy in patients with virologic failure receiving indinavir (IDV). Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:159 (abstract no 490)

    BACKGROUND
  • Hammer SM, Bassett R, Squires KE, Fischl MA, Demeter LM, Currier JS, Mellors JW, Morse GD, Eron JJ, Santana JL, DeGruttola V; ACTG 372B/D Study Team. A randomized trial of nelfinavir and abacavir in combination with efavirenz and adefovir dipivoxil in HIV-1-infected persons with virological failure receiving indinavir. Antivir Ther. 2003 Dec;8(6):507-18. No abstract available.

    PMID: 14760884BACKGROUND
  • Hammer SM, Ribaudo H, Bassett R, Mellors JW, Demeter LM, Coombs RW, Currier J, Morse GD, Gerber JG, Martinez AI, Spreen W, Fischl MA, Squires KE; AIDS Clinical Trials Group (ACTG) 372A Study Team. A randomized, placebo-controlled trial of abacavir intensification in HIV-1-infected adults with virologic suppression on a protease inhibitor-containing regimen. HIV Clin Trials. 2010 Nov-Dec;11(6):312-24. doi: 10.1310/hct1106-312.

MeSH Terms

Conditions

HIV Infections

Interventions

IndinavirabacavirNelfinavirefavirenzCarnitineadefovir dipivoxilLamivudineStavudineZidovudineDidanosine

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

PyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoquinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingTrimethyl Ammonium CompoundsQuaternary Ammonium CompoundsAminesOrganic ChemicalsZalcitabineDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesDideoxynucleosidesThymidineInosinePurine NucleosidesPurinesRibonucleosides

Study Officials

  • Scott Hammer

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Masking
DOUBLE
Purpose
TREATMENT
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 2, 1999

First Posted

August 31, 2001

Study Completion

June 1, 2003

Last Updated

October 28, 2021

Record last verified: 2021-10

Locations