To determine the proportion of patients whose plasma HIV-1 RNA level falls below the level of detection (< 400 copies/ml) at week 24 of study therapy. To determine the absolute change in plasma HIV-1 RNA during the 24 weeks of study treatment. To collect safety data on the treatment regimens. AS PER AMENDMENT 12/12/97: To compare the virologic response of Fortovase (FTV) (Saquinavir) Soft Gel Capsule (SGC) tid plus nucleoside reverse transcriptase inhibitors (NRTIs) versus FTV bid plus NRTIs. Further, to compare the virologic response of FTV tid plus NRTIs versus FTV bid plus Nelfinavir bid plus a NRTI with respect to: the percentage of patients whose plasma HIV-1 RNA level falls below the Amplicor assay level of detection (< 400 copies/ml) at week 24 and week 48.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Ritonavir  Drug: Nelfinavir mesylate  Drug: Saquinavir  Drug: Delavirdine mesylate  Drug: Lamivudine  Drug: Stavudine  Drug: Zidovudine	Phase III

Further Study Details: 

Expected Total Enrollment:  825

Patients will be randomized to receive 1 of 3 study regimens: Group A - Saquinavir (SQV) sgc plus 2 new reverse transcriptase inhibitors (RTIs), Group B - SQV sgc plus delavirdine plus new RTI, and Group C - SQV sgc plus nelfinavir plus new RTI, or SQV sgc plus ritonavir plus 2 new RTIs. NOTE: "New RTI" is defined for this study as any reverse transcriptase inhibitor to which the patient has never been exposed. AS PER AMENDMENT 12/12/97: In this open-label, multicenter, Phase IIIB, comparative study, 825 patients are randomized to treatment arms. (NOTE: 50% of the patients will be treatment naive and 50% will be NRTI experienced.) Further, patients are randomized with stratification based on HIV-1 RNA level (5,000-30,000 copies/ml vs. greater than 30,000 copies/ml) and prior antiretroviral therapy to one of the three study arms. The drug regimens for the three treatment arms are as follows: ARM A: Fortovase (FTV), plus 2 new NRTIs*. ARM B: FTV plus 2 new NRTIs*. ARM C: FTV plus nelfinavir plus new NRTI**. * Naive patients in Arm A and Arm B will take: d4T (or zidovudine) plus 3TC unless contraindicated. ** Naive patients in Arm C will take: d4T, unless contraindicated. * NRTI experienced patients in Arms A & B should be treated with 2 NRTIs to which he/she has not been previously exposed. If the patient has only 1 NRTI to which he/she has never been exposed, then the second NRTI can be one that the patient has been previously exposed to from the most distant past. Therapy is administered for an initial 24 weeks and may be extended for an additional 24 weeks.

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

Criteria

Inclusion Criteria

Patients must have:

• HIV-1 infection.
• HIV RNA >= 5000 copies/ml by Amplicor assay.
• Signed, informed consent from parent or legal guardian for patients less than 18 years old. Prior Medication: Required: (Note:
• 50% of the patients will be treatment naive).
• > 3 months cumulative therapy with antiretrovirals other than non-nucleoside reverse transcriptase inhibitors and/or protease inhibitors.
• Stable antiretroviral therapy for at least 4 weeks prior to enrollment. Allowed:
• <= 2 weeks cumulative treatment with protease inhibitors. AS PER AMENDMENT 12/12/97: Required: NRTI experienced patients:
• > 3 months cumulative therapy with antiretrovirals.
• <= 2 weeks cumulative previous treatment with non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs).
• <= 2 weeks cumulative previous treatment with protease inhibitors.
• Must have at least one NRTI (preferably two) to which he/she has not been previously exposed.
• Stable antiretroviral therapy defined as within (+/-) 1 log HIV-1 RNA between the 2 most recent values greater than 8 weeks apart (may include screening visit) prior to study enrollment. (NOTE:
• If patient does not have a previous HIV-1 RNA value, screening will be accepted.)

Required:

• Note:
• 50% of the patients will be treatment naive and 50% will be NRTI experienced. AS PER AMENDMENT 12/12/97.

Alabama
      ASC Inc, Aniston,  Alabama,  36201,  United States
Arizona
      CIGNA, Phoenix,  Arizona,  85006,  United States
      Arizona Clinical Research Ctr Inc, Tucson,  Arizona,  85712,  United States
      Univ of Arizona, Tucson,  Arizona,  85724,  United States
California
      Marin County Specialty Clinic, San Rafael,  California,  94903,  United States
      Kaiser Permanente Med Ctr, San Francisco,  California,  94115,  United States
      Shared Med Research Foundation, Tarzana,  California,  91356,  United States
      AIDS Community Research Consortium, Redwood City,  California,  94063,  United States
      UCSF - San Francisco Gen Hosp, San Francisco,  California,  94110,  United States
      QUEST Clinical Research, San Francisco,  California,  94115,  United States
      Dr Charles Farthing, Los Angeles,  California,  90048,  United States
      AIDS Healthcare Foundation Labs, Los Angeles,  California,  90027,  United States
      Beer Med Group, Los Angeles,  California,  90036,  United States
      Alta Bates Med Ctr, Berkeley,  California,  94705,  United States
      Ctr for Special Immunology, Irving,  California,  92718,  United States
      Gottlieb Med Group, North Hollywood,  California,  91607,  United States
      Dr Wilbert Jordan, Paramount,  California,  90723,  United States
      Dr Daniel Pearce, San Francisco,  California,  92101,  United States
Colorado
      Denver Public Health Dept / Disease Control Services, Denver,  Colorado,  80204,  United States
      Kaiser Permanente, Infectious Disease, Denver,  Colorado,  80205,  United States
District of Columbia
      Georgetown Univ Med Ctr, Washington,  District of Columbia,  20007,  United States
      Anderson Clinical Research, Washington,  District of Columbia,  20037,  United States
      Providence Hosp, Washington,  District of Columbia,  20037,  United States
Florida
      Univ of South Florida, Tampa,  Florida,  33612,  United States
      Infectious Disease Research Institute Inc, Tampa,  Florida,  33614,  United States
      Stratogen of Ft Lauderdale, Fort Lauderdale,  Florida,  33334,  United States
      Steinhart Medical Associates, Miami,  Florida,  33133,  United States
      IDC Research Initiative, Altamonte Springs,  Florida,  32701,  United States
      Dr Robert Schwartz, Fort Myers,  Florida,  33901,  United States
      Ctr for Quality Care, Tampa,  Florida,  33609,  United States
      Treasure Coast Infectious Disease Consultants, Vero Beach,  Florida,  32960,  United States
      Stratogen Health of Palm Beach, Palm Beach Gardens,  Florida,  33410,  United States
      Duval County Health Dept, Jacksonville,  Florida,  32206,  United States
      Urgent Care Ctr, Fort Lauderdale,  Florida,  33316,  United States
Georgia
      AIDS Research Consortium of Atlanta, Atlanta,  Georgia,  30308,  United States
      Infectious Disease Specialists of Atlanta, Decatur,  Georgia,  30033,  United States
Illinois
      Northwestern Univ Med Ctr, Chicago,  Illinois,  60611,  United States
      SIU School of Medicine, Springfield,  Illinois,  62702,  United States
      Carle Clinic Association, Urbana,  Illinois,  61801,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
Kentucky
      Univ of Kentucky / Kentucky Clinic Annex #, Lexington,  Kentucky,  40536,  United States
Massachusetts
      Univ of Massachusetts Med Ctr, Worcester,  Massachusetts,  01655,  United States
      Community Research Initiative, Brookline,  Massachusetts,  02445,  United States
      Community Research Initiative, Brookline,  Massachusetts,  02445,  United States
Michigan
      Harper Hosp, Detroit,  Michigan,  48201,  United States
      Saint Joseph's / Mercy Hosp, Ypsilanti,  Michigan,  48197,  United States
Minnesota
      Abbott Northwestern Hosp, Minneapolis,  Minnesota,  55407,  United States
      Mayo Clinic, Rochester,  Minnesota,  55905,  United States
Missouri
      Univ of Missouri at Kansas City School of Medicine, Kansas City,  Missouri,  64108,  United States
      Antibiotic Research Associates, Kansas City,  Missouri,  64132,  United States
Nevada
      HIV Wellness Ctr / Univ Med Ctr, Las Vegas,  Nevada,  89102,  United States
New Hampshire
      Dartmouth-Hitchcock Med Ctr, Lebanon,  New Hampshire,  03756,  United States
New Jersey
      UMDNJ - New Jersey Med School / Cooper Hosp, Camden,  New Jersey,  08103,  United States
      New Jersey Community Research Initiative, Newark,  New Jersey,  07103,  United States
      VAMC New Jersey Healthcare System, East Orange,  New Jersey,  07018,  United States
      St Joseph's Hosp & Med Center, Paterson,  New Jersey,  07503,  United States
New York
      North Shore Univ Hosp, Manhasset,  New York,  11030,  United States
      Albany Med College / Division of HIV Medicine A158, Albany,  New York,  122083479,  United States
      Harlem Hosp Ctr, New York,  New York,  10037,  United States
      New York Hosp - Cornell Med Ctr, New York,  New York,  10021,  United States
      Dr Douglas Dieterich, New York,  New York,  10016,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263,  United States
      Liberty Med Group, New York,  New York,  10016,  United States
      New York Hosp / Cornell Med Ctr, New York,  New York,  10021,  United States
      Nassau County Med Ctr, East Meadow,  New York,  11554,  United States
      Mt Vernon Hosp, Mt. Vernon,  New York,  10550,  United States
      Howard Grossman, New York,  New York,  10011,  United States
      Dr Ron Grossman, New York,  New York,  10016,  United States
      AIDS Clinical Trials Unit, New York,  New York,  10016,  United States
      Brookdale Univ Med Ctr, Brooklyn,  New York,  11212,  United States
      Montefiore Med Ctr, Bronx,  New York,  10467,  United States
      Elmhurst Hosp, Elmhurst,  New York,  11373,  United States
      Peter Krueger Clinic, New York,  New York,  10003,  United States
      Dr Michael Mullen, New York,  New York,  10003,  United States
      New York / Cornell Med Ctr, New York,  New York,  10021,  United States
      St Lukes / Roosevelt Hosp / HIV Center, New York,  New York,  10019,  United States
North Carolina
      Nalle Clinic, Charlotte,  North Carolina,  28207,  United States
      East Carolina Univ School of Medicine, Greenville,  North Carolina,  27858,  United States
      Bowman Gray School of Medicine, Winston Salem,  North Carolina,  27157,  United States
      Carolinas Research Associates, Charlotte,  North Carolina,  28203,  United States
Ohio
      Univ of Cincinnati Med Ctr / Holmes Division, Cincinnati,  Ohio,  45267,  United States
Oklahoma
      Oklahoma Univ Health Science Ctr, Oklahoma City,  Oklahoma,  73104,  United States
Pennsylvania
      Allegheny Univ Hosp, Philadelphia,  Pennsylvania,  19129,  United States
      Lehigh Valley Hosp, Allentown,  Pennsylvania,  18105,  United States
      Dr Jay Kostman, Philadelphia,  Pennsylvania,  19140,  United States
Rhode Island
      Roger Williams Med Ctr, Providence,  Rhode Island,  02908,  United States
South Carolina
      Burnside Clinic, Columbia,  South Carolina,  29206,  United States
Texas
      Houston Clinical Research Network, Houston,  Texas,  77004,  United States
      Houston Med Ctr, Houston,  Texas,  77030,  United States
      ONCOL Med Associates / PA, Houston,  Texas,  77027,  United States
      Austin Infectious Disease Consultants, Austin,  Texas,  78705,  United States
      Dr Nicholaos Bellos, Dallas,  Texas,  75225,  United States
      Houston Clinical Research Network, Houston,  Texas,  77098,  United States
      North Texas Infectious Disease Consultants, Dallas,  Texas,  75246,  United States
      Univ of Texas Southwestern Med Ctr of Dallas, Dallas,  Texas,  75235,  United States
Virginia
      Infectious Disease Physicians Inc, Annandale,  Virginia,  22203,  United States
Washington
      Swedish Med Ctr / Dr Peter Shalit, Seattle,  Washington,  98104,  United States
Wisconsin
      Aurora Med Group, Milwaukee,  Wisconsin,  53212,  United States
Germany
      Medizinische Einrichtungen der Heinrich U, Duesseldorf,  Germany
Italy
      Ospedale S Raffaele, Milano,  Italy
Puerto Rico
      San Juan Veterans Administration Med Ctr, San Juan,  009275800,  Puerto Rico
Spain
      Hosp Valle D Hebron, Barcelona,  Spain
United Kingdom
      Royal Liverpool Univ Hosp, Liverpool,  United Kingdom

Study ID Numbers:  229H; NR15520; M6101
Record last reviewed:  December 1998
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00002378
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08