To determine the clinical efficacy of indinavir sulfate or placebo in combination with zidovudine ( AZT ) and lamivudine ( 3TC ) in AIDS patients. Protease inhibitors such as indinavir sulfate may be effective in patients with advanced HIV disease who have received prior AZT therapy. Since studies suggest that triple drug therapy may have an advantage over both monotherapy and two drug therapy, the combination of indinavir sulfate with AZT and 3TC should be evaluated.

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

Further Study Details: 

Expected Total Enrollment:  1750

Protease inhibitors such as indinavir sulfate may be effective in patients with advanced HIV disease who have received prior AZT therapy. Since studies suggest that triple drug therapy may have an advantage over both monotherapy and two drug therapy, the combination of indinavir sulfate with AZT and 3TC should be evaluated.

Patients are randomized to receive open-label AZT and 3TC with or without indinavir sulfate for at least 48 weeks. Patients who develop intolerance to AZT or have progressive disease after 24 weeks on study may substitute stavudine ( d4T ) for AZT. Patients are followed at weeks 4, 8, 16, 24, 32, 40, and 48 and every 8 weeks thereafter up to week 96. [AS PER 02/25/97 AMENDMENT: Accrual has been halted because interim analysis has shown triple therapy superior to double-agent therapy. An open label extension phase has been added for the period through 06/30/97. Patients who had been randomized to AZT/3TC are given the option of continuing on assigned ACTG 320 study drugs, crossing over to open-label indinavir, or permanently discontinuing all study therapies and going off study. Patients who were randomized to AZT/3TC plus indinavir or who were crossed to such therapy are given the option of continuing their currently assigned therapies. It is strongly suggested that patients who were on AZT/3TC who wish to receive open-label indinavir consider changing the nucleoside analog component of their regimen if at all possible.] [ AS PER 06/06/97 AMENDMENT: The availability of the current ACTG 320 treatment has been further extended for approximately 12 additional weeks (but not beyond 09/30/97). This extension will allow patients to continue receiving study medications until ACTG 372 is open to accrual (the rollover protocol for subjects originally randomized to the triple drug component of ACTG 320 or who are crossed over due to a confirmed study endpoint is finalized).] [ AS PER 09/15/97 AMENDMENT: Open-label therapy will be provided for no more than 90 days beyond the enrollment of the first subject on ACTG 372.]

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

Criteria

Inclusion Criteria

Concurrent Medication: Required:

• PCP prophylaxis.

Allowed:

• Topical or oral antifungal agents (other than oral ketoconazole).
• Approved agents for opportunistic infections.
• Antibiotics unless specifically excluded.
• Systemic corticosteroids for no more than 21 days.
• Vitamins.
• Recombinant erythropoietin.
• G-CSF.
• Regularly prescribed medications such as allergy medications, antidepressants, antipyretics, analgesics, oral contraceptives, megestrol, and testosterone.

Concurrent Treatment: Allowed:

• Acupuncture.
• Visualization techniques.

Patients must have:

• HIV infection.
• CD4 count <= 200 cells/mm3.
• At least 6 months total prior AZT therapy.

Exclusion Criteria

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

• Malignancy requiring systemic therapy other than minimal Kaposi's sarcoma.

Concurrent Medication: Excluded:

• Antiretrovirals other than study drugs.
• Rifabutin and rifampin.
• Investigational drugs other than indinavir sulfate.
• Systemic cytotoxic chemotherapy.
• Oral ketoconazole.
• Chronic systemic corticosteroids.
• Herbal therapies.

Patients with the following prior conditions are excluded:

• Unexplained temperature > 38.5 C for any 7 days within 30 days prior to study entry.
• Chronic diarrhea persisting for 15 days within 30 days prior to study entry.
• History of acute or chronic pancreatitis.
• Acute hepatitis within 30 days prior to study entry.
• Grade 2 or worse bilateral peripheral neuropathy within 60 days prior to study entry.
• Dose-limiting intolerance to prior AZT at 600 mg/day.

Prior Medication: Excluded:

• More than 1 week of prior 3TC.
• Any prior protease inhibitors.
• Rifampin or rifabutin within 14 days prior to study entry.

Excluded within 30 days prior to study entry:

• Erythropoietin.
• G-CSF or GM-CSF.
• Non-nucleoside reverse transcriptase inhibitors.
• Interferons.
• Interleukins.
• HIV vaccines.
• Any experimental therapy.

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  United States
      Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco,  California,  94115,  United States
      San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
      San Francisco AIDS Clinic / San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
      Stanford Univ Med Ctr, Stanford,  California,  943055107,  United States
      UCLA CARE Ctr, Los Angeles,  California,  90095,  United States
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States
      Children's Hosp of Los Angeles, Los Angeles,  California,  90027,  United States
      Harbor UCLA Med Ctr, Torrance,  California,  90502,  United States
      San Mateo AIDS Program / Stanford Univ, Stanford,  California,  943055107,  United States
Colorado
      Mountain States Reg Hemo Ctr / Univ of Colorado, Denver,  Colorado,  80262,  United States
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
      Kaiser Permanente Franklin Med Ctr, Denver,  Colorado,  80262,  United States
District of Columbia
      Howard Univ, Washington,  District of Columbia,  20059,  United States
      George Washington Univ / Hershey Med Ctr, Washington,  District of Columbia,  20037,  United States
      Georgetown Univ Hosp, Washington,  District of Columbia,  20037,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
      Univ of Miami (Pediatric), Miami,  Florida,  33161,  United States
Georgia
      Emory Univ, Atlanta,  Georgia,  30308,  United States
      Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr, Atlanta,  Georgia,  303652225,  United States
Hawaii
      Queens Med Ctr, Honolulu,  Hawaii,  96816,  United States
      Univ of Hawaii, Honolulu,  Hawaii,  96816,  United States
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  606143394,  United States
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
      Rush Presbyterian - Saint Luke's Med Ctr, Chicago,  Illinois,  60612,  United States
      Illinois Masonic Med Ctr, Chicago,  Illinois,  606575147,  United States
      Louis A Weiss Memorial Hosp, Chicago,  Illinois,  60640,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
      Methodist Hosp of Indiana / Life Care Clinic, Indianapolis,  Indiana,  46202,  United States
      Division of Inf Diseases/ Indiana Univ Hosp, Indianapolis,  Indiana,  46202,  United States
Iowa
      Univ of Iowa Hosp and Clinic, Iowa City,  Iowa,  52242,  United States
Louisiana
      Charity Hosp / Tulane Univ Med School, New Orleans,  Louisiana,  70112,  United States
      Tulane Univ School of Medicine, New Orleans,  Louisiana,  70112,  United States
      Tulane Med Ctr Hosp, New Orleans,  Louisiana,  70112,  United States
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States
      State of MD Div of Corrections / Johns Hopkins Univ Hosp, Baltimore,  Maryland,  212052196,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States
      Boston Med Ctr, Boston,  Massachusetts,  02118,  United States
      Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial, Worcester,  Massachusetts,  01605,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States
      St Paul Ramsey Med Ctr, St. Paul,  Minnesota,  55101,  United States
      Hennepin County Med Clinic, Minneapolis,  Minnesota,  55415,  United States
Missouri
      St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis,  Missouri,  63112,  United States
Nebraska
      Univ of Nebraska Med Ctr, Omaha,  Nebraska,  681985130,  United States
New York
      St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr, New York,  New York,  10021,  United States
      Harlem Hosp Ctr, New York,  New York,  10037,  United States
      North Shore Univ Hosp, Great Neck,  New York,  11021,  United States
      SUNY / State Univ of New York, Syracuse,  New York,  13210,  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
      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  United States
      Manhattan Veterans Administration / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States
      Cornell Univ Med Ctr, New York,  New York,  10021,  United States
      Mount Sinai Med Ctr / Pediatrics, New York,  New York,  10029,  United States
      Bronx Veterans Administration / Mount Sinai Hosp, Bronx,  New York,  10468,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      Mount Sinai Med Ctr / Hemophilia Treatment Ctr, New York,  New York,  10029,  United States
      Beth Israel Med Ctr, New York,  New York,  10003,  United States
      Saint Clare's Hosp and Health Ctr, New York,  New York,  10019,  United States
      Kaplan Cancer Ctr / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Montefiore Med Ctr Adolescent AIDS Program, Bronx,  New York,  10467,  United States
North Carolina
      Central Prison/Women's Prison in Raleigh / NC, Raleigh,  North Carolina,  276260540,  United States
      Carolinas Med Ctr, Charlotte,  North Carolina,  28203,  United States
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
      Moses H Cone Memorial Hosp, Greensboro,  North Carolina,  27401,  United States
      Duke Univ Med Ctr, Durham,  North Carolina,  27710,  United States
Ohio
      Case Western Reserve Univ, Cleveland,  Ohio,  44106,  United States
      Univ of Cincinnati, Cincinnati,  Ohio,  452670405,  United States
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
      Columbus Children's Hosp, Columbus,  Ohio,  432052696,  United States
      Univ of Kentucky Lexington, Cincinnati,  Ohio,  45267,  United States
Pennsylvania
      Thomas Jefferson Univ Hosp, Philadelphia,  Pennsylvania,  191075098,  United States
      Milton S Hershey Med Ctr, Hershey,  Pennsylvania,  170330850,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
      Med Univ of South Carolina, Charleston,  South Carolina,  294253312,  United States
Tennessee
      Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr, Knoxville,  Tennessee,  37920,  United States
      Meharry Med College, Nashville,  Tennessee,  37203,  United States
      Vanderbilt Univ Med Ctr, Nashville,  Tennessee,  37203,  United States
Texas
      Univ Texas Health Science Ctr / Univ Texas Med School, Houston,  Texas,  77030,  United States
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States
Washington
      Univ of Washington, Seattle,  Washington,  981224304,  United States
Wisconsin
      Great Lakes Hemophilia Foundation, Wauwatosa,  Wisconsin,  532130127,  United States
Puerto Rico
      Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon,  00956,  Puerto Rico
      Univ of Puerto Rico, San Juan,  009365067,  Puerto Rico

Study chairs or principal investigators

Hammer SM,  Study Chair
Squires KE,  Study Chair
Fischl MA,  Study Chair

Study ID Numbers:  ACTG 320
Record last reviewed:  April 1999
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000841
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08