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

October 27, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Activity of the Soft Gelatin Capsule of Saquinavir (SQVsgc) in Combination With Ritonavir or Nelfinavir and Combinations of Delavirdine and/or Adefovir Dipivoxil in HIV-Infected Subjects With Prior Indinavir Use and Viral Loads From 2,000 to 200,000 Copies HIV RNA/ml

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Patients are stratified by HIV RNA (2,000 - 20,000 copies/ml versus 20,000 - 200,000 copies/ml), and randomized to 1 of 6 treatment arms as follows:

Arm A: Saquinavir (SQV) plus ritonavir (RTV) plus delavirdine (DLV) plus adefovir dipivoxil placebo.

Arm B: SQV plus RTV plus DLV placebo plus adefovir dipivoxil. Arm C: SQV plus RTV plus DLV plus adefovir dipivoxil. Arm D: SQV plus nelfinavir (NFV) plus DLV plus adefovir dipivoxil placebo. Arm E: SQV plus NFV plus DLV placebo plus adefovir dipivoxil. Arm F: SQV plus NFV plus DLV plus adefovir dipivoxil. In addition to assigned study treatment patients receive an L-carnitine supplement.

Therapy is administered for 24 weeks. Patients who have an average HIV RNA value for Weeks 12 and 16 that is less than 5,000 copies or a least 1 log below their baseline value may continue their assigned study treatment for an additional 24 weeks. [AS PER AMENDMENT 3/30/98: Subjects with plasma HIV RNA greater than 5,000 copies/ml may elect to continue or discontinue study medications in the treatment extension and seek the best available treatment.] [AS PER AMENDMENT 06/11/98: The dose of adefovir dipivoxil is reduced at or after Week 16. Alternatively, patients may discontinue adefovir dipivoxil/placebo and substitute appropriate antiretroviral agent(s) or add appropriate antiretroviral agent(s) to their reduced-dose regimen. Also, at the discretion of the protocol chairperson, patients who have been on study for more than 16 weeks may substitute appropriate FDA-approved antiretroviral agent(s) for any study medication that must be discontinued because of toxicity. Addition of nonnucleoside reverse transcriptase inhibitors, protease inhibitors, or investigational agents is specifically excluded.]

Study Type

Interventional

Enrollment

300

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Univ of Alabama at Birmingham
    • California
      • Los Angeles, California, United States, 90095
        • UCLA CARE Ctr
      • Los Angeles, California, United States, 900331079
        • Univ of Southern California / LA County USC Med Ctr
      • Menlo Park, California, United States, 94025
        • Willow Clinic
      • San Diego, California, United States, 921036325
        • Univ of California / San Diego Treatment Ctr
      • San Francisco, California, United States, 94115
        • Stanford at Kaiser / Kaiser Permanente Med Ctr
      • San Francisco, California, United States, 941102859
        • San Francisco Gen Hosp
      • San Jose, California, United States, 951282699
        • Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
      • Stanford, California, United States, 943055107
        • San Mateo AIDS Program / Stanford Univ
      • Stanford, California, United States, 943055107
        • Stanford Univ Med Ctr
      • Torrance, California, United States, 90502
        • Harbor UCLA Med Ctr
    • Colorado
      • Denver, Colorado, United States, 80262
        • Univ of Colorado Health Sciences Ctr
    • District of Columbia
      • Washington, District of Columbia, United States, 20059
        • Howard Univ
    • Florida
      • Miami, Florida, United States, 331361013
        • Univ of Miami School of Medicine
    • Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Univ of Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Queens Med Ctr
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Univ Med School
      • Chicago, Illinois, United States, 60612
        • Rush Presbyterian - Saint Luke's Med Ctr
      • Chicago, Illinois, United States, 60612
        • Cook County Hosp
      • Chicago, Illinois, United States, 60640
        • Louis A Weiss Memorial Hosp
    • Indiana
      • Indianapolis, Indiana, United States, 462025250
        • Indiana Univ Hosp
      • Indianapolis, Indiana, United States, 46202
        • Methodist Hosp of Indiana / Life Care Clinic
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hosp
      • Baltimore, Maryland, United States, 212052196
        • State of MD Div of Corrections / Johns Hopkins Univ Hosp
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Med Ctr
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess - West Campus
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Univ of Minnesota
    • New York
      • Buffalo, New York, United States, 14215
        • SUNY / Erie County Med Ctr at Buffalo
      • New York, New York, United States, 10003
        • Beth Israel Med Ctr
      • New York, New York, United States, 10021
        • Cornell Univ Med Ctr
      • New York, New York, United States, 10016
        • Bellevue Hosp / New York Univ Med Ctr
      • New York, New York, United States, 10029
        • Mount Sinai Med Ctr
      • New York, New York, United States, 10021
        • Chelsea Ctr
      • New York, New York, United States, 10021
        • St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr
      • Rochester, New York, United States, 14642
        • Univ of Rochester Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 275997215
        • Univ of North Carolina
    • Ohio
      • Cincinnati, Ohio, United States, 452670405
        • Univ of Cincinnati
      • Columbus, Ohio, United States, 432101228
        • Ohio State Univ Hosp Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Univ of Pennsylvania at Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213
        • Univ of Pittsburgh Med Ctr
    • Rhode Island
      • Providence, Rhode Island, United States, 02908
        • Brown Univ School of Medicine
    • South Carolina
      • West Columbia, South Carolina, United States, 29169
        • Julio Arroyo
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
    • Texas
      • Galveston, Texas, United States, 775550435
        • Univ of Texas Galveston
    • Washington
      • Seattle, Washington, United States, 981224304
        • Univ of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

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.
  • 2,000 to 200,000 HIV-1 RNA copies/ml as measured by any Roche-certified laboratory [AS

PER AMENDMENT 3/30/98:

  • using the Roche Amplicor HIV-1 Monitor] within 30 days of study entry.
  • Signed, informed consent from parent or legal guardian for patients less than 18 years of age.

Prior Medication: Required:

  • More than 6 months cumulative indinavir therapy.
  • Stable indinavir-containing antiretroviral regimen for at least 4 weeks [2 weeks AS PER AMENDMENT 3/30/98] prior to study entry.

Exclusion Criteria

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).
  • NNRTIs (nevirapine, delavirdine, DMP-266, etc.), saquinavir (soft gelatin capsule), nelfinavir, 141W94VX-478, and adefovir dipivoxil.
  • Immunomodulator [systemic immunomodulator AS PER AMENDMENT 3/30/98] or investigational drug therapy within 30 days prior to entry.
  • Active immunization within 30 days [21 days AS PER AMENDMENT 3/30/98] prior to entry.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: R Gulick
  • Study Chair: D Katzenstein

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

August 1, 1999

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

November 4, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 359
  • 11324 (Registry Identifier: DAIDS ES)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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