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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002179
• Other study ID #: 246G
• Secondary ID: MK-0639
• Status: Completed
• Phase: Phase 4
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: June 1999
• Source: NIH AIDS Clinical Trials Information Service
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Indinavir sulfate

• Lamivudine

• Zidovudine

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Canada,