A Study of the Effectiveness of Different Anti-HIV Treatments in HIV-Positive Individuals Who Have Been on a Protease Inhibitor-Containing Drug Regimen for at Least 16 Weeks

A Randomized Study of the Virologic Efficacy of Different Antiretroviral (AR) Treatment Strategies in HIV-Infected Individuals With Detectable Plasma HIV RNA Measurements After at Least 16 Weeks on Their Initial Protease Inhibitor-Containing AR Regimens

The purpose of this study is to compare different treatments for HIV infection to see which works best to lower HIV levels and to raise the number of CD4 cells (cells of the immune system that fight infection), in HIV-positive individuals who have been on a protease inhibitor-containing drug regimen for at least 16 weeks.

Researchers have found that combination anti-HIV therapy (multiple drugs given together) can help prevent AIDS-related illnesses and help people with AIDS live longer. In this study, the anti-HIV drug efavirenz (EFV) will be tested with 1 or 2 other protease inhibitors (PIs) to see which combination works best to treat HIV infection. EFV has been shown to limit the amount of HIV virus produced by infected cells.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Indinavir sulfate; Drug: Ritonavir; Drug: Nelfinavir mesylate; Drug: Efavirenz

Detailed Description

Current recommendations for the initial treatment of HIV infection have centered on the reduction of plasma HIV levels. It has been shown that a combination of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and a PI is the most effective barriers to disease progression. This study attempts to demonstrate these data.

Two options are available for patients whose initial PI-containing regimen has failed to suppress viral replication.

Option 1 consists of immediate versus deferred use of a nonnucleoside reverse transcriptase inhibitor (NNRTI). Patients who choose Option 1 are randomized to 1 of 2 groups:

1. Ritonavir (RTV) plus soft gelatin capsule saquinavir (SQV-SGC) plus efavirenz (EFV).
2. RTV plus SQV-SGC.

Option 2 consists of treatment with a single PI versus double PI. Patients who choose Option 2 are randomized to 1 of 2 groups:

1. Nelfinavir (NFV) plus EFV.
2. RTV plus SQV-SGC plus EFV.

Patients failing NFV in Option 2 are randomized to one of two groups:

1. Indinavir (IDV) plus EFV.
2. RTV plus SQV-SGC plus EFV. Patients remain on study treatment regimens for 8 weeks. Follow-up visits, including history and physical evaluations, take place at specified intervals during the next 12 months.

• Study Type: Interventional
• Enrollment: 800
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • Community Consortium / UCSF
  • Colorado
    • Denver, Colorado, United States, 802044507
      • Denver CPCRA / Denver Public Hlth
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • Washington Reg AIDS Prog / Dept of Infect Dis
  • Georgia
    • Atlanta, Georgia, United States, 303081962
      • AIDS Research Consortium of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60657
      • AIDS Research Alliance - Chicago
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hosp
    • Detroit, Michigan, United States, 48201
      • Wayne State Univ - WSU/DMC / Univ Hlth Ctr
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Southern New Jersey AIDS Cln Trials / Dept of Med
    • Newark, New Jersey, United States, 071032842
      • North Jersey Community Research Initiative
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Partners in Research / New Mexico
  • New York
    • New York, New York, United States, 10037
      • Harlem AIDS Treatment Grp / Harlem Hosp Ctr
  • Oregon
    • Portland, Oregon, United States, 97210
      • The Research and Education Group
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
  • Virginia
    • Richmond, Virginia, United States, 232980049
      • Richmond AIDS Consortium / Div of Infect Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

You may be eligible for this study if you:

• Are HIV-positive.
• Have an HIV RNA count of at least 400 copies/ml.
• Are at least 13 years old (need consent if under 18).
• Have been on antiretroviral treatment (including at least 2 NRTIs) for at least 16 weeks prior to study entry.
• Agree to practice abstinence or to use effective methods of birth control, including a barrier method, during the study.

Exclusion Criteria

You will not be eligible for this study if you:

• Are pregnant or breast-feeding.
• Have active opportunistic (HIV-associated) infections.
• Have taken nelfinavir (NFV) for more than 2 weeks after failing indinavir/ritonavir (IDV/RTV) treatment or have taken IDV/RTV for more than 2 weeks after failing NFV treatment.
• Have used any protease inhibitor other than NFV or IDV/RTV for more than 2 weeks.
• Have used any non-nucleoside reverse transcriptase inhibitor (NNRTI) for more than 1 week.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Jay R. Kostman; Study Chair: Lawrence R. Crane

Publications and helpful links

General Publications

• Mannheimer S, Friedland G, Matts J, Child C, Chesney M. Antiretroviral adherence correlates with quality of life. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 485)

Study record dates

Study Major Dates

• Study Completion (Actual): June 1, 2000

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): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Reverse Transcriptase Inhibitors; Viral Load; HIV Protease Inhibitors; Nelfinavir; Ritonavir; Indinavir; Saquinavir
• 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; Protease Inhibitors; 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; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Ritonavir; Indinavir; Nelfinavir; Efavirenz
• Other Study ID Numbers: CPCRA 057; 11610 (Registry Identifier: DAIDS ES)