A Study of Abacavir Plus Indinavir Sulfate Plus Efavirenz in HIV-Infected Patients

NCT00001086 | Completed Phase 2

• 2 other identifiers: ACTG 36811331
• Study Type: interventional
• Target: 300
• Locations: 2 countries
• Sites: 56

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.

Conditions

HIV Infections

Keywords

Placebos; HIV-1; Drug Therapy, Combination; HIV Protease Inhibitors; Indinavir; RNA, Viral; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Viral Load; efavirenz

Interventions

Indinavir sulfate DRUG

Abacavir sulfate DRUG

Efavirenz DRUG

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Concurrent Medication:
• Allowed:
• Chemoprophylaxis for Pneumocystis carinii pneumonia is required for all patients who have a CD4 cell count \<= 200 cells/mm3.
• Topical and/or oral antifungal agents are permitted except for oral ketoconazole.
• Treatment, maintenance or chemoprophylaxis with approved agents for opportunistic infections as clinically indicated, except for rifabutin.
• All antibiotics as clinically indicated.
• Systemic corticosteroid use for \<= 21 days for acute problems is permitted as medically indicated; chronic systemic corticosteroid use is not permitted, unless it is within physiologic replacement levels.
• Recombinant erythropoietin and granulocyte colony-stimulating factor are permitted as medically indicated.
• Regularly prescribed medications such as antipyretics, analgesics, allergy medications (except for terfenadine (Seldane) and astemizole (Hismanal)), antidepressants, sleep medications, oral contraceptives, megestrol acetate, testosterone or any other medications are permitted as medically indicated.
• NOTE:
• Due to the possibility that EFV or ABC may alter the effectiveness of oral contraceptives or depo-progesterone, oral contraceptives or depo-progesterone must not be used as the sole form of birth control. \[AS PER AMENDMENT 8/7/98: adequate birth control is hormonal plus barrier method or two barrier methods\].
• Alternative therapies such as vitamins, acupuncture, and visualization techniques will be permitted. Herbal medications should be avoided. Patients should report the use of these therapies; alternative therapies will be recorded. \[AS PER AMENDMENT 8/7/98: Due to the likelihood of IDV increasing the concentrations of sildenafil (Viagra) when coadministered, it is suggested that subjects who use viagra take the lowest dose (25 mg, i.e., half the typical dose).\]
• Both NIAID ACTG 320 participants and non-ACTG 320 patients must have:
• Documented HIV-1 infection.
• Written informed consent from parent or legal guardian for those patients \< 18 years old.

You may not qualify if:

• Co-existing Condition:
• Non-ACTG 320 patients with the following symptoms and conditions are excluded:
• Malignancy that requires systemic therapy other than minimal Kaposi's sarcoma.
• NOTE:
• Minimal Kaposi's sarcoma, defined as \<= 5 cutaneous lesions and no visceral disease or tumor-associated edema, allowed, provided systemic therapy not required.
• Non-ACTG 320 patients with the following prior conditions or symptoms are excluded:
• Unexplained temperature \> 38.5 degrees C for 7 consecutive days.
• Chronic diarrhea defined as \> 3 liquid stools per day persisting for 15 days, within 30 days prior to entry.
• Proven or suspected acute hepatitis within 30 days prior to entry, even if AST (SGOT) and ALT (SGPT) are \<= 5 X ULN.
• Concurrent Medication: Excluded:
• All antiretroviral therapies other then study medications.
• Rifabutin and rifampin.
• Investigational drugs without specific approval from the protocol chair.
• Systemic cytotoxic chemotherapy.
• Oral ketoconazole (Nizoral), terfenadine (Seldane), astemizole (Hismanal), cisapride (Propulsid), triazolam (Halcion), and midazolam (Versed).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (56)

Univ of Southern California / LA County USC Med Ctr

Los Angeles, California, 900331079, United States

Location

UCLA CARE Ctr

Los Angeles, California, 90095, United States

Location

San Francisco Gen Hosp

San Francisco, California, 941102859, United States

Location

Stanford at Kaiser / Kaiser Permanente Med Ctr

San Francisco, California, 94115, United States

Location

Stanford Univ Med Ctr

Stanford, California, 943055107, 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

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

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

Univ of Iowa Hosp and Clinic

Iowa City, Iowa, 52242, United States

Location

Charity Hosp / Tulane Univ Med School

New Orleans, Louisiana, 70112, United States

Location

Tulane Med Ctr Hosp

New Orleans, Louisiana, 70112, United States

Location

Tulane Univ School of Medicine

New Orleans, Louisiana, 70112, United States

Location

State of MD Div of Corrections / Johns Hopkins Univ Hosp

Baltimore, Maryland, 212052196, 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

Hennepin County Med Clinic

Minneapolis, Minnesota, 55415, United States

Location

Univ of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

St Paul Ramsey Med Ctr

Saint Paul, Minnesota, 55101, 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

Saint Clare's Hosp and Health Ctr

New York, New York, 10019, 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

Duke Univ Med Ctr

Durham, North Carolina, 27710, United States

Location

Moses H Cone Memorial Hosp

Greensboro, North Carolina, 27401, United States

Location

Central Prison/Women's Prison in Raleigh / NC

Raleigh, North Carolina, 276260540, United States

Location

Univ of Cincinnati

Cincinnati, Ohio, 452670405, United States

Location

Univ of Kentucky Lexington

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve Univ

Cleveland, Ohio, 44106, United States

Location

Ohio State Univ Hosp Clinic

Columbus, Ohio, 432101228, United States

Location

Milton S Hershey Med Ctr

Hershey, Pennsylvania, 170330850, United States

Location

Univ of Pennsylvania at Philadelphia

Philadelphia, Pennsylvania, 19104, 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 of Washington

Seattle, Washington, 981224304, United States

Location

Great Lakes Hemophilia Foundation

Wauwatosa, Wisconsin, 532130127, United States

Location

Univ of Puerto Rico

San Juan, 009365067, Puerto Rico

Location

Related Publications (4)

• Squires K, Hammer S, Degruttola V, Fischl M, Grimes J, Demeter L, Morse G. Randomized trial of abacavir (ABC) in combination with indinavir (IDV) and efavirenz (EFV) in HIV-infected patients (pts) with nucleoside analog experience (NRTI exp). Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:207 (abstract no LB15)

  BACKGROUND

• Dicenzo R, Forrest A, Smith P, Squires K, Hammer S, Fischl M, Degruttola V, Morse G. Comparing intensive and sparse sampling for estimating the population pharmacokinetics (PK) of indinavir (IDV) in efavirenz (EFV)containing regimens. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 751)

  BACKGROUND

• Landay AL, Bettendorf D, Chan E, Spritzler J, Schmitz JL, Bucy RP, Gonzalez CJ, Schnizlein-Bick CT, Evans T, Squires KE, Phair JP. Evidence of immune reconstitution in antiretroviral drug-experienced patients with advanced HIV disease. AIDS Res Hum Retroviruses. 2002 Jan 20;18(2):95-102. doi: 10.1089/08892220252779638.

  PMID: 11839142 BACKGROUND

• Demeter LM, DeGruttola V, Lustgarten S, Bettendorf D, Fischl M, Eshleman S, Spreen W, Nguyen BY, Koval CE, Eron JJ, Hammer S, Squires K. Association of efavirenz hypersusceptibility with virologic response in ACTG 368, a randomized trial of abacavir (ABC) in combination with efavirenz (EFV) and indinavir (IDV) in HIV-infected subjects with prior nucleoside analog experience. HIV Clin Trials. 2008 Jan-Feb;9(1):11-25. doi: 10.1310/hct0901-11.

  PMID: 18215978 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Indinavir; abacavir; efavirenz

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Squires KE

  STUDY CHAIR

• Hammer SM

  STUDY CHAIR

• Fischl MA

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: September 1, 1999
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

PR (1); US (55)