The Effectiveness of Indinavir Plus Zidovudine Plus Lamivudine in HIV-Infected Patients With No Symptoms of Infection

A Multiclinic, Open Study to Evaluate the Ability of the Combination of Indinavir, Zidovudine and Lamivudine to Result in Sustained Suppression of HIV-1 in Asymptomatic HIV-1 Seropositive Patients

To evaluate the ability of the combination of indinavir, zidovudine, and lamivudine to suppress HIV-1 infection as measured by: (1) the maintenance of HIV-1 serum viral RNA below the limit of detection of the most sensitive validated assay (ultradirect assay) and (2) absence of evidence of infectious virus in lymph node, cerebrospinal fluid (CSF), peripheral mononuclear cells (PBMCs), and semen.

It is hypothesized that the administration of indinavir, zidovudine, and lamivudine will result in:

1. No evidence of infectious virus in lymph node tissue, CSF, PBMCs, and semen samples in 50% of patients who have undetectable viral RNA by the most sensitive validated assay available (ultradirect assay) for at least 48 weeks.
2. Sustained suppression of HIV-1 infection as measured by a decrease in serum viral RNA to below the limit of detection of the ultradirect assay for at least 48 weeks in at least 25% of patients.
3. Suppression of HIV-1 infection as measured by a decrease in serum viral RNA to below the limit of detection of the standard Amplicor assay (i.e., negative) in at least 90% of patients by Week 16.
4. Suppression of HIV-1 infection, suggesting eradication of the virus as measured by maintenance of serum viral RNA to below the limit of detection of the ultradirect assay for at least 24 weeks after discontinuation of indinavir, zidovudine, and lamivudine in patients who have maintained this level of suppression for at least 120 weeks on therapy.

Study Overview

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

Detailed Description

It is hypothesized that the administration of indinavir, zidovudine, and lamivudine will result in:

1. No evidence of infectious virus in lymph node tissue, CSF, PBMCs, and semen samples in 50% of patients who have undetectable viral RNA by the most sensitive validated assay available (ultradirect assay) for at least 48 weeks.
2. Sustained suppression of HIV-1 infection as measured by a decrease in serum viral RNA to below the limit of detection of the ultradirect assay for at least 48 weeks in at least 25% of patients.
3. Suppression of HIV-1 infection as measured by a decrease in serum viral RNA to below the limit of detection of the standard Amplicor assay (i.e., negative) in at least 90% of patients by Week 16.
4. Suppression of HIV-1 infection, suggesting eradication of the virus as measured by maintenance of serum viral RNA to below the limit of detection of the ultradirect assay for at least 24 weeks after discontinuation of indinavir, zidovudine, and lamivudine in patients who have maintained this level of suppression for at least 120 weeks on therapy.

All patients receive indinavir plus zidovudine plus lamivudine for at least 96 weeks. If there is no evidence of infectious virus, and patients continue to have serum viral RNA levels below the limit of detection of the ultradirect assay for at least 96 weeks, therapy is continued for an additional 24 weeks. However, during this additional 24 weeks of therapy patients may continue to receive this triple combination drug regimen or make changes to this drug regimen treatment by reducing their number of antiretroviral agents. After 120 weeks, if patients continue to have serum viral RNA levels below the limit of detection of the ultradirect assay, patients discontinue all antiretroviral therapy. However, if there is any evidence of infectious virus, as outlined above, patients do not discontinue therapy. Patients who develop detectable serum viral RNA following discontinuation of therapy are given the option to reinitiate therapy with the triple combination of indinavir, zidovudine and lamivudine. NOTE: Patients who develop an intolerance to zidovudine may use stavudine at doses per body weight at the direction of the investigator.

• Study Type: Interventional
• Enrollment: 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Saint Paul's Hosp
  • Quebec
    • Montreal, Quebec, Canada
      • Montreal Gen Hosp
• United States
  • Alabama
    • Birmingham, Alabama, United States, 352942050
      • Univ of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90033
      • LAC - USC Med Ctr
    • Redwood City, California, United States, 94063
      • AIDS Community Research Consortium
    • San Francisco, California, United States, 94110
      • San Francisco Gen Hosp
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Univ School of Medicine / AIDS Program
  • Illinois
    • Chicago, Illinois, United States, 606123832
      • Rush Presbyterian - Saint Luke's Med Ctr / Infect Dis
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hosp
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Harvard (Massachusetts Gen Hosp)
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hosp
    • Boston, Massachusetts, United States, 02115
      • Fenway Community Health Ctr
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Med Ctr - East Campus
  • New York
    • New York, New York, United States, 10016
      • NYU Med Ctr
    • Stony Brook, New York, United States, 117948153
      • Univ Hosp / SUNY at Stony Brook / AIDS TMT Unit
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Pitt Treatment Ctr
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Brown Univ / Miriam Hosp

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

Patients must have:

• HIV-1 seropositive status.
• CD4 count >= 500 cells/mm3.
• Serum viral RNA level > 1000 copies/ml.

Exclusion Criteria

Prior Medication:

Excluded:

Previous antiretroviral therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: December 7, 2022
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022

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): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: June 1, 1999

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Reverse Transcriptase Inhibitors; Anti-HIV Agents; HIV-1; Lamivudine; RNA, Viral; Viral Load; Zidovudine; HIV Protease Inhibitors; Indinavir; Semen; Monocytes; Lymph Nodes
• Additional Relevant MeSH Terms: 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; HIV Protease Inhibitors; Viral Protease Inhibitors; Lamivudine; Zidovudine; Indinavir
• Other Study ID Numbers: 246G; MK-0639

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No