To determine, in HIV-infected patients, whether switching to a new soft gelatin capsule formulation of saquinavir or to indinavir following prolonged use of the original hard capsule formulation of saquinavir results in an acute decrease in plasma HIV RNA. Resistance to anti-HIV agents occurs with increasing duration of use. In vitro studies have shown that cross-resistance occurs among protease inhibitors, although no clinical trials have been conducted to examine antiretroviral activity with sequential use of protease inhibitors or to determine whether saquinavir resistance can be overcome with higher concentrations of the drug.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Indinavir sulfate  Drug: Saquinavir	Phase II

Further Study Details: 

Expected Total Enrollment:  144

Resistance to anti-HIV agents occurs with increasing duration of use. In vitro studies have shown that cross-resistance occurs among protease inhibitors, although no clinical trials have been conducted to examine antiretroviral activity with sequential use of protease inhibitors or to determine whether saquinavir resistance can be overcome with higher concentrations of the drug.

Patients who are currently receiving hard capsule saquinavir are randomized to continue receiving hard capsule saquinavir or to switch to soft gelatin capsule saquinavir or indinavir. At week 8, patients receiving the hard capsule formulation will switch to open-label indinavir for weeks 8-24. Patients on the other two arms will remain on their assigned regimen for the entire 24 weeks unless they have no virologic response by week 8, in which case they will be crossed-over to open-label therapy with the alternative drug (i.e., either soft gelatin capsule saquinavir or indinavir). AS PER AMENDMENT 12/23/96: Viral RNA from weeks 16 and 24 will be assayed in batch after week 24. Patients who exhibit an antiviral response based on this assay will be allowed to continue their current drug assignment for a total of 12 months. AS PER AMENDMENT 5/7/97: Based on an interim analysis performed after 72 patients had completed 8 weeks of therapy, the study was closed as of March 7, 1997. Patients currently enrolled may stop their participation in the trial and seek other anti-retroviral therapies or may continue on study. Patients on hard capsule saquinavir who remain on study will be switched to indinavir at 8 weeks. Patients on soft gel capsule saquinavir may switch immediately to indinavir or, when results of HIV RNA and CD4 cell counts are available, may choose to switch to indinavir or remain on soft gel capsule saquinavir. Patients receiving indinavir will continue that agent. Follow-up for all patients will end on 7/4/97.

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

Criteria

Inclusion Criteria

Concurrent Medication: Required:

• PCP prophylaxis if CD4 count <= 200 cells/mm3.

Allowed:

• Intralesional therapy for KS.
• Vitamins.
• Nucleoside RT inhibitors, provided regimen remains stable for first 8 weeks of study.

Concurrent Treatment: Allowed:

• Acupuncture.
• Visualization techniques.

Patients must have:

• HIV infection.
• Prior hard capsule saquinavir at 1800 mg/day for more than 1 year.

Prior Medication: Allowed:

• Prior saquinavir.
• Prior antiretrovirals, excluding protease inhibitors other than saquinavir.

Exclusion Criteria

Co-existing Condition: Patients with the following symptoms or conditions are excluded:

• Psychological condition or medical instability that would interfere with study evaluation or procedures.

AS PER AMENDMENT 5/7/97:

• Active tuberculosis.

Concurrent Medication: Excluded:

• Protease inhibitors other than study drugs.
• Non-nucleoside RT inhibitors.
• Interferon.
• Interleukins.
• GM-CSF.
• HIV vaccines.
• Systemic cytotoxic chemotherapy.
• Investigational drugs other than study medications.
• Rifabutin.
• Rifampin.
• Midazolam.
• Triazolam.
• Ketoconazole.
• Delavirdine.
• Cisapride.
• Terfenadine.
• Astemizole.

AS PER AMENDMENT 5/7/97:

• Nevirapine.

Patients with the following prior conditions are excluded:

• Unexplained fever > 38.5 C for any 7 days within 30 days prior to study entry.
• Diarrhea persisting for 15 days within 30 days prior to study entry.

Prior Medication: Excluded:

• Any prior protease inhibitor other than saquinavir.

Excluded within the past 2 months.

• Change in antiretroviral regimen.
• Systemic chemotherapy for KS.

Excluded within the past month:

• Non-nucleoside RT inhibitors.
• Interferons.
• Interleukins.
• HIV vaccines.
• Experimental therapies.

Excluded within the past 2 weeks:

• Rifabutin.
• Cisapride.
• Terfenadine.
• Astemizole.
• Midazolam.
• Triazolam.
• Oral ketoconazole.
• Delavirdine.
• Acute therapy for infection or other medical illness.

Active substance abuse that would interfere with study evaluation or procedures.

California
      Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco,  California,  94115,  United States
      San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
      Stanford Univ Med Ctr, Stanford,  California,  943055107,  United States
      Children's Hosp of Oakland, Oakland,  California,  946091809,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
      Rush Presbyterian - Saint Luke's Med Ctr, Chicago,  Illinois,  60612,  United States
Louisiana
      Tulane Univ School of Medicine, New Orleans,  Louisiana,  70112,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
Missouri
      St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis,  Missouri,  63112,  United States
New York
      St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr, New York,  New York,  10021,  United States
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      Beth Israel Med Ctr, New York,  New York,  10003,  United States
Ohio
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Texas
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States
Washington
      Univ of Washington, Seattle,  Washington,  981224304,  United States

Study chairs or principal investigators

Para MF,  Study Chair
Collier A,  Study Chair
Coombs R,  Study Chair

Study ID Numbers:  ACTG 333
Record last reviewed:  June 1999
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000848
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08