A Study of Several Anti-HIV Drug Combinations in HIV-Infected Patients Who Have Used Indinavir

NCT00000892 | Completed

• 2 other identifiers: ACTG 35911324
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 45

Brief Summary

To compare the proportion of patients whose plasma HIV-1 RNA is below 500 copies/ml after 16 weeks of treatment. To assess the safety, toxicity, and tolerance of each treatment arm. While indinavir is currently the most commonly prescribed protease inhibitor, the optimal therapy for a person on an indinavir-containing regimen who experiences a rebound in viral load or never experiences a decrease in viral load below 500 copies per milliliter is unknown. Current clinical practice for such patients typically involves empiric use of a combination of other protease inhibitors (saquinavir/nelfinavir or saquinavir/ritonavir) and at least 1 other antiretroviral agent to which the patient has had little or no prior exposure. This may involve the use of 1 or more reverse transcriptase inhibitors (RTIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs). This study attempts to formally evaluate some of these options in indinavir-experienced patients.

Conditions

HIV Infections

Keywords

HIV-1; Drug Therapy, Combination; HIV Protease Inhibitors; Ritonavir; Indinavir; RNA, Viral; Saquinavir; Delavirdine; Nelfinavir; Adenine; Anti-HIV Agents; Viral Load

Interventions

Ritonavir DRUG

Nelfinavir mesylate DRUG

Levocarnitine DRUG

Adefovir dipivoxil DRUG

Saquinavir DRUG

Delavirdine mesylate 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:
• Required:
• Chemoprophylaxis for Pneumocystis carinii pneumonia for all patients who have a CD4 cell count of equal or less than 200 cells/mm3.
• Allowed:
• Topical and oral antifungal agents except ketoconazole and itraconazole.
• Treatment, maintenance or chemoprophylaxis with approved agents for opportunistic infections.
• Antibiotics.
• Systemic corticosteroids for 21 days or less for acute problems.
• Recombinant erythropoietin (rEPO) and granulocyte-colony stimulating factor (G-CSF, filgrastim).
• Regularly prescribed medications such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives (not as a sole form of birth control), megestrol acetate, or testosterone.
• Alternative therapies, such as vitamins, acupuncture, and visualization techniques.
• \[AS PER AMENDMENT 3/30/98: Calcium channel blockers may be used only with caution.\]
• Patients must have:
• HIV-1 infection documented by a licensed ELISA and confirmed by Western blot, HIV culture, HIV antigen, plasma HIV RNA, or a second antibody test other than ELISA.
• ,000 to 200,000 HIV-1 RNA copies/ml as measured by any Roche-certified laboratory \[AS

You may not qualify if:

• Co-existing Condition:
• Patients with the following conditions or symptoms are excluded:
• Any active infection requiring acute treatment within 30 days \[21 days AS PER AMENDMENT 3/30/98\] prior to study entry.
• Unexplained temperature greater than 38.5 degrees for any 7 consecutive days within 30 days prior to study entry.
• Malignancy, including Kaposi's sarcoma, that requires systemic chemotherapy.
• Concurrent Medication:
• Excluded:
• Non-protocol-specified immunomodulatory and/or antiretroviral agents.
• Systemic cytotoxic chemotherapy.
• Ketoconazole, itraconazole, rifampin, rifabutin, alprazolam, amiodarone, astemizole, bepridil, bupropion, cisapride, clorazepate, clozapine, diazepam, encainide, estazolam, flecainide, flurazepam, isotretinoin, meperidine, midazolam, piroxicam, propafenone, propoxyphene, quinidine, terfenadine, triazolam, zolpidem, phenytoin, phenobarbital, carbamazepine, and ergot alkaloids and \[ AS PER AMENDMENT 3/30/98: dexamethasone, ergot derivatives, and pimozide\].
• Avoided:
• Herbal medications.
• Prior Medication:
• Excluded:
• At least 2 weeks or more total ritonavir and/or saquinavir (hard gelatin capsule).

Sponsors & Collaborators

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

Study Sites (45)

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

UCLA CARE Ctr

Los Angeles, California, 90095, United States

Location

Willow Clinic

Menlo Park, California, 94025, United States

Location

Univ of California / San Diego Treatment Ctr

San Diego, California, 921036325, 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

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

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

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

Methodist Hosp of Indiana / Life Care Clinic

Indianapolis, Indiana, 46202, 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

Boston Med Ctr

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess - West Campus

Boston, Massachusetts, 02215, United States

Location

Univ of Minnesota

Minneapolis, Minnesota, 55455, 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

Univ of Cincinnati

Cincinnati, Ohio, 452670405, United States

Location

Ohio State Univ Hosp Clinic

Columbus, Ohio, 432101228, United States

Location

Univ of Pennsylvania at Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Univ of Pittsburgh Med Ctr

Pittsburgh, Pennsylvania, 15213, United States

Location

Brown Univ School of Medicine

Providence, Rhode Island, 02908, 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

Univ of Texas Galveston

Galveston, Texas, 775550435, United States

Location

Univ of Washington

Seattle, Washington, 981224304, United States

Location

Related Publications (10)

• Gulick RM, Hu XJ, Fiscus S, Fletcher CV, Haubrich R, Cheng H, Lagakos S, Acosta E, Swanstrom R, Mills C, Snyder S, Fischl M, Pettinelli C, Katzenstein D. Durability of salvage therapy with saquinavir SGC (SQV) in combination with ritonavir (RTV) or nelfinavir (NFV) plus delavirdine (DLV), adefovir dipivoxil (ADV), or both; ACTG 359: 48-week final results. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 338)

  BACKGROUND

• Acosta EP, Gulick R, Katzenstein D, Haubrich R, Fischl M, Raasch R, Mills C, Pettinelli C, Remmel RP, Fletcher CV. Pharmacokinetic (PK) evaluation of saquinavir soft gel capsules (SQV)/ritonavir (RTV) or sqv/nelfinavir (NFV) in combination with delavirdine (DLV) and/or adefovir dipivoxil (ADV) - - ACTG 359. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:136 (abstract no 365)

  BACKGROUND

• Gulick RM, et al. Salvage therapy with saquinavir sgc (SQV) in combination with ritonavir (RTV) or nelfinavir (NFV) and delavirdine (DLV), adefovir dipivoxil (ADV), or both-ACTG 359. Second International Workshop on Salvage Therapy for HIV Infection. 1999 May 19-21

  BACKGROUND

• Fletcher CV, Testa MA, Haubrich R, Brundage R, Jiang H, Ickovics J, Martinez A, Snyder S, Gulick R. Relationships among Four Measures of Medication Adherence and Virologic Response in ACTG 359. 10th Conference on Retroviruses and Oppurtunistic Infections. Feb 2003. Abstract 577.

  BACKGROUND

• Gulick RM, Hu XJ, Fiscus SA, Fletcher CV, Haubrich R, Cheng H, Acosta E, Lagakos SW, Swanstrom R, Freimuth W, Snyder S, Mills C, Fischl M, Pettinelli C, Katzenstein D. Randomized study of saquinavir with ritonavir or nelfinavir together with delavirdine, adefovir, or both in human immunodeficiency virus-infected adults with virologic failure on indinavir: AIDS Clinical Trials Group Study 359. J Infect Dis. 2000 Nov;182(5):1375-84. doi: 10.1086/315867. Epub 2000 Oct 9.

  PMID: 11023461 RESULT

• Gulick RM, Hu XJ, Fiscus SA, Fletcher CV, Haubrich R, Cheng H, Acosta E, Lagakos SW, Swanstrom R, Freimuth W, Snyder S, Mills C, Fischl M, Pettinelli C, Katzenstein D. Durability of response to treatment among antiretroviral-experienced subjects: 48-week results from AIDS Clinical Trials Group Protocol 359. J Infect Dis. 2002 Sep 1;186(5):626-33. doi: 10.1086/342681. Epub 2002 Aug 9.

  PMID: 12195349 RESULT

• Fletcher CV, Jiang H, Brundage RC, Acosta EP, Haubrich R, Katzenstein D, Gulick RM. Sex-based differences in saquinavir pharmacology and virologic response in AIDS Clinical Trials Group Study 359. J Infect Dis. 2004 Apr 1;189(7):1176-84. doi: 10.1086/382754. Epub 2004 Mar 16.

  PMID: 15031785 RESULT

• Swanstrom R, Bosch RJ, Katzenstein D, Cheng H, Jiang H, Hellmann N, Haubrich R, Fiscus SA, Fletcher CV, Acosta EP, Gulick RM; AIDS Clinical Trials Group Protocol 359 Team. Weighted phenotypic susceptibility scores are predictive of the HIV-1 RNA response in protease inhibitor-experienced HIV-1-infected subjects. J Infect Dis. 2004 Sep 1;190(5):886-93. doi: 10.1086/422692. Epub 2004 Jul 23.

  PMID: 15295692 RESULT

• Fletcher CV, Testa MA, Brundage RC, Chesney MA, Haubrich R, Acosta EP, Martinez A, Jiang H, Gulick RM. Four measures of antiretroviral medication adherence and virologic response in AIDS clinical trials group study 359. J Acquir Immune Defic Syndr. 2005 Nov 1;40(3):301-6. doi: 10.1097/01.qai.0000180078.53321.6a.

  PMID: 16249704 RESULT

• Haubrich RH, Jiang H, Swanstrom R, Bates M, Katzenstein D, Petch L, Fletcher CV, Fiscus SA, Gulick RM; AIDS Clinical Trials Group Protocol 359 Team. Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359. HIV Clin Trials. 2007 Mar-Apr;8(2):63-7. doi: 10.1310/hct0802-63.

  PMID: 17507321 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Ritonavir; Nelfinavir; Carnitine; adefovir dipivoxil; Saquinavir; Delavirdine

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)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Quinolines; Piperazines; Indoles

Study Officials

• R Gulick

  STUDY CHAIR

• D Katzenstein

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: August 1, 1999
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

US (45)