A Study to Compare The Ability of Different Anti-HIV Drugs to Decrease Viral Load After Nelfinavir (an Anti-HIV Drug)Treatment Failure

A Phase II, Randomized, Open-Label Comparative Trial of Salvage Antiretroviral Therapies for HIV-Infected Individuals With Virological Evidence of Nelfinavir Treatment Failure as Reflected by Plasma HIV RNA Concentration of >= 1,000 Copies/ml

The purpose of this study is to determine the safety and effectiveness of combining several anti-HIV drugs in order to decrease plasma viral load (level of HIV in the blood) in HIV-positive patients who have failed nelfinavir (NFV) treatment.

In order to determine the ability of a drug regimen to decrease viral load after drug treatment has failed, it is best to test a variety different of drug "cocktails" (drug regimens). The drug cocktails in this study include 2 new nucleoside reverse transcriptase inhibitors (NRTIs), efavirenz (an NNRTI, non-nucleoside reverse transcriptase inhibitor), and either 1 or 2 protease inhibitors. It is important to include multiple drugs from different groups in a drug cocktail since combinations containing fewer drugs are likely to fail.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Indinavir sulfate; Drug: Lamivudine; Drug: Stavudine; Drug: Zidovudine; Drug: Ritonavir; Drug: Didanosine; Drug: Amprenavir; Drug: Efavirenz; Drug: Saquinavir; Drug: Lamivudine/Zidovudine

Detailed Description

To maximize the likelihood of a favorable response to salvage therapy, 4 or 5 drug regimens should be studied. Regimens containing fewer drugs, particularly those lacking a non-nucleoside reverse transcriptase inhibitor (NNRTI) such as efavirenz, are likely to result in an unacceptable rate of virological failure. Therefore, this study examines drug combinations which include two new nucleoside reverse transcriptase inhibitors (NRTIs), the NNRTI efavirenz, and either one or two protease inhibitors which are known not to produce cross-resistance to nelfinavir.

Patients are randomly selected to receive 1 of the following 4 treatment regimens:

Arm A: Ritonavir, saquinavir, efavirenz, and 2 new NRTIs. Arm B: Indinavir, efavirenz and 2 new NRTIs. Arm C: Amprenavir, efavirenz, and 2 new NRTIs. [AS PER AMENDMENT 3/22/00: Patients have the option to increase the APV dose or to add low-dose ritonavir. APV will continue to be provided by the study; ritonavir will not be provided by the study.] Arm D: Indinavir, amprenavir, efavirenz, and 2 new NRTIs. [AS PER AMENDMENT 6/28/99: All treatment regimens must include at least 1 new NRTI.] [AS PER AMENDMENT 3/22/00: ACTG 400 will continue to provide originally randomized study medications to all patients until approximately May 10, 2000, regardless of virologic response. Patients may also add antiretrovirals of their choice to this regimen (not provided by the study).] Clinical assessments are taken at Weeks 2, 4, 8, 12, 16, and every 8 weeks thereafter for the duration of the study. In addition, 2 substudies are being conducted: a drug-interaction substudy and a drug-exposure substudy. [AS PER AMENDMENT 3/22/00: Both substudies are closed to accrual and their pharmacokinetics assessments are discontinued.]

• Study Type: Interventional
• Enrollment: 300
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 009365067
    • Univ of Puerto Rico
• 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 Francisco, California, United States, 941102859
      • San Francisco AIDS Clinic / San Francisco Gen Hosp
    • 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
    • San Rafael, California, United States, 94903
      • Marin County Specialty Clinic
    • Stanford, California, United States, 943055107
      • San Mateo AIDS Program / Stanford Univ
    • Stanford, California, United States, 943055107
      • Stanford Univ 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
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory Univ
  • 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
  • Indiana
    • Indianapolis, Indiana, United States, 462025250
      • Indiana Univ Hosp
    • Indianapolis, Indiana, United States, 46202
      • Methodist Hosp of Indiana / Life Care Clinic
    • Indianapolis, Indiana, United States, 46202
      • Division of Inf Diseases/ Indiana Univ Hosp
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Harvard (Massachusetts Gen Hosp)
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess - West Campus
  • Missouri
    • St Louis, Missouri, United States, 63112
      • St Louis Regional Hosp / St Louis Regional Med Ctr
  • 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
    • Rochester, New York, United States, 14642
      • Univ of Rochester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 275997215
      • Univ of North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Univ Med Ctr
  • Ohio
    • Cincinnati, Ohio, United States, 452670405
      • Univ of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve Univ
    • Columbus, Ohio, United States, 432101228
      • Ohio State Univ Hosp Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Univ of Pennsylvania at Philadelphia
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Julio Arroyo
  • Washington
    • Seattle, Washington, United States, 98104
      • Univ of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Patients may be eligible for this study if they:

• Are over 13 years old (need consent of parent or guardian if under 18).
• Are HIV-positive.
• Currently have virologic failure (more than 1,000 copies of HIV RNA per ml).
• Agree to abstinence or use of effective birth control during the study.
• Have been taking NFV for the past 12 weeks.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Have a fever for 7 days or diarrhea for 30 days before study entry.
• Have a history of peripheral neuropathy within 60 days of study entry.
• Have hepatitis.
• Have any malignancy (cancer) other than minimal Kaposi's sarcoma.
• Are pregnant or breast-feeding.
• Are receiving radiation, chemotherapy, or any therapy for any illness within 14 days of study entry.
• Have taken amprenavir, saquinavir, indinavir or ritonavir for more than 7 days.
• Have received an HIV vaccine 30 days before study entry.
• Are receiving certain other medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Scott Hammer; Study Chair: John Mellors; William Powderly

Study record dates

Study Major Dates

• Study Completion (Actual): February 1, 2002

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 (Estimate): May 21, 2012
• Last Update Submitted That Met QC Criteria: May 17, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Viral Load; HIV Protease Inhibitors; Salvage Therapy
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Ritonavir; Lamivudine; Zidovudine; Stavudine; Indinavir; Didanosine; Efavirenz; Amprenavir; Saquinavir; Lamivudine, zidovudine drug combination
• Other Study ID Numbers: ACTG 400; 11356 (Registry Identifier: DAIDS ES Registry Number); Substudy A5013s; Substudy A5022s