The Addition of Indinavir to Anti-HIV Treatment in HIV-Infected Patients

A Randomized Trial of Immediate Versus Deferred Indinavir in Addition to Background Antiretroviral Therapy in HIV-Infected Patients With CD4+ Cell Counts Between 200 and 500/mm3 and Plasma HIV RNA Levels >= 10,000 Copies/ml

The purpose of this study is to evaluate the effect of immediate versus deferred indinavir (IDV) in addition to background therapy on disease progression or death in patients with CD4+ cell counts between 200 and 500 cells/mm3 and plasma HIV RNA levels >= 10,000 copies/ml.

This study aims to examine two management strategies, immediate versus deferred IDV therapy, for their clinical effects in the context of background antiretroviral (AR) therapy, given according to current clinical practice. There is an urgent need to identify the optimal use of IDV in patient management, since clinical endpoint studies have not been completed in the United States. Since there is little information about the long term durability of clinical effects, and even less information about the timing of the initiation of protease inhibitor therapy, exploring the disease progression and survival impact of immediate versus delayed use of IDV will yield important information to guide clinical decision making for this group of patients.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Indinavir sulfate

Detailed Description

This study aims to examine two management strategies, immediate versus deferred IDV therapy, for their clinical effects in the context of background antiretroviral (AR) therapy, given according to current clinical practice. There is an urgent need to identify the optimal use of IDV in patient management, since clinical endpoint studies have not been completed in the United States. Since there is little information about the long term durability of clinical effects, and even less information about the timing of the initiation of protease inhibitor therapy, exploring the disease progression and survival impact of immediate versus delayed use of IDV will yield important information to guide clinical decision making for this group of patients.

Prior to randomization the patient and clinician will determine whether the background therapy will be zidovudine (ZDV) plus lamivudine (3TC) or other background antiretroviral therapy (OBAT). Patients will then be randomized to IDV or matching placebo. AS PER AMENDMENT 06/27/97: The protocol was closed as of 03/25/97, and all patients have been unblinded to their assigned treatment. Patients still on study medication are eligible for the protocol extension. Patients who were randomized to immediate IDV may continue on therapy for up to an additional 4 months. All study therapy, both for those on immediate or delayed therapy, must be discontinued on 10/24/97.

• Study Type: Interventional
• Enrollment: 1900
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • Community Consortium of San Francisco
  • Colorado
    • Denver, Colorado, United States, 802044507
      • Denver CPCRA / Denver Public Hlth
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • Veterans Administration Med Ctr / Regional AIDS Program
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • 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
      • Comprehensive AIDS Alliance of Detroit
  • 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 York
    • New York, New York, United States, 10037
      • Harlem AIDS Treatment Group / Harlem Hosp Ctr
  • Oregon
    • Portland, Oregon, United States, 972109951
      • Portland Veterans Adm Med Ctr / Rsch & Education Grp
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Richmond AIDS Consortium

Participation Criteria

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:

Allowed:

• Topical and/or antifungal agents, except ketoconazole.
• Treatment, maintenance, or chemoprophylaxis with approved agents for OIs will be given as clinically indicated.
• Clinically indicated antibiotics, unless excluded.
• Systemic corticosteroid use for <21 days for acute problems is permitted as clinically indicated. However, chronic systemic corticosteroid use should be avoided.
• Recombinant erythropoietin (rEPO) and granulocyte-colony stimulating factor (G-CSF, filgrastim).
• Didanosine (ddI).
• Regularly prescribed medications, such as antipyretics, antidepressants, oral contraceptives, megestrol acetate, testosterone, or any other medication.

Patients must have:

• A working diagnosis of HIV infection.
• A CD4+ count between 200 and 500 cells/mm3.
• Signed, informed parental consent if patient is less than 18.

NOTE:

• The DAIDS Clinical Science Research Committee (CSRC) has deemed this protocol appropriate for prisoner enrollment.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following conditions or symptoms are excluded:

Febrile illness with temperature > 38.5 degrees C (101.3 degrees F) within 3 days prior to study entry.

Concurrent Medication:

Excluded:

• Non-nucleoside reverse transcriptase inhibitors.
• Protease inhibitors except IDV.
• Rifabutin and rifampin.
• Ketoconazole.
• Terfenadine, astemizole, cisapride, triazolam and midazolam.

Patients with any of the following prior conditions are excluded:

• History of prior saquinavir (SQV) therapy for more than 14 days.
• History of any prior protease inhibitor therapy other than SQV.
• History of serious opportunistic infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: Double

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Saravolatz L; Study Chair: Mayers D

Publications and helpful links

General Publications

• Spector SA, Barker C, Buhles W, Feinberg J, Montague P, Weingeist T, DeArmond B. A randomized, controlled study of immediate vs deferred ganciclovir therapy in AIDS patients with cytomegalovirus peripheral retinitis. Int Conf AIDS. 1991 Jun 16-21;7(1):44 (abstract no MB86)

Study record dates

Study Major Dates

• Study Completion (Actual): March 1, 1997

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 28, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Anti-HIV Agents; RNA, Viral; Viral Load; CD4 Lymphocyte Count; HIV Protease Inhibitors; Drug Administration Schedule; Indinavir
• 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; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Indinavir
• Other Study ID Numbers: CPCRA 041; 11591 (Registry Identifier: DAIDS ES Registry Number)