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.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Indinavir sulfate  Drug: Lamivudine  Drug: Zidovudine	Phase IV

Further Study Details: 

Expected Total Enrollment:  200

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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.

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

Study ID Numbers:  246G; MK-0639
Record last reviewed:  June 1999
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00002179
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08