Clinical trial NCT00002179: The Effectiveness of Indinavir Plus Zidovudine Plus Lamivudine in HIV-Infected Patients With No Symptoms of Infection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: Semen
Monocytes
HIV-1
Drug Therapy, Combination
Zidovudine
Lymph Nodes
HIV Protease Inhibitors
Lamivudine
Indinavir
RNA, Viral
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
First posted: 2001-08-31
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

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