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.

Condition	Treatment or Intervention
HIV Infections	Drug: Indinavir sulfate

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.

Ages Eligible for Study:  16 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

California
      Community Consortium of San Francisco, San Francisco,  California,  94110,  United States
Colorado
      Denver CPCRA / Denver Public Hlth, Denver,  Colorado,  802044507,  United States
District of Columbia
      Veterans Administration Med Ctr / Regional AIDS Program, Washington,  District of Columbia,  20422,  United States
Georgia
      AIDS Research Consortium of Atlanta, Atlanta,  Georgia,  30308,  United States
Illinois
      AIDS Research Alliance - Chicago, Chicago,  Illinois,  60657,  United States
Louisiana
      Louisiana Comm AIDS Rsch Prog / Tulane Univ Med, New Orleans,  Louisiana,  70112,  United States
Michigan
      Henry Ford Hosp, Detroit,  Michigan,  48202,  United States
      Comprehensive AIDS Alliance of Detroit, Detroit,  Michigan,  48201,  United States
New Jersey
      North Jersey Community Research Initiative, Newark,  New Jersey,  071032842,  United States
      Southern New Jersey AIDS Cln Trials / Dept of Med, Camden,  New Jersey,  08103,  United States
New York
      Harlem AIDS Treatment Group / Harlem Hosp Ctr, New York,  New York,  10037,  United States
Oregon
      Portland Veterans Adm Med Ctr / Rsch & Education Grp, Portland,  Oregon,  972109951,  United States
Pennsylvania
      Philadelphia FIGHT, Philadelphia,  Pennsylvania,  19107,  United States
Virginia
      Richmond AIDS Consortium, Richmond,  Virginia,  23298,  United States

Study chairs or principal investigators

Saravolatz L,  Study Chair
Crane L,  Study Chair
Mayers D,  Study Chair

Study ID Numbers:  CPCRA 041
Record last reviewed:  April 1997
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000861
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-14