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.
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.]
Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon 00956, Puerto Rico
Univ of Puerto Rico, San Juan 009365067, Puerto Rico
Univ of Alabama at Birmingham, Birmingham, Alabama 35294, United States
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
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
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
Univ of Miami School of Medicine, Miami, Florida 331361013, United States
Univ of Miami (Pediatric), Miami, Florida 33161, United States
Emory Univ, Atlanta, Georgia 30308, United States
Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr, Atlanta, Georgia 303652225, United States
Queens Med Ctr, Honolulu, Hawaii 96816, United States
Univ of Hawaii, Honolulu, Hawaii 96816, United States
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 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
Univ of Iowa Hosp and Clinic, Iowa City, Iowa 52242, United States
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
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
State of MD Div of Corrections / Johns Hopkins Univ Hosp, Baltimore, Maryland 212052196, United States
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
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
St Louis Regional Hosp / St Louis Regional Med Ctr, St Louis, Missouri 63112, United States
Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States
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
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
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
Thomas Jefferson Univ Hosp, Philadelphia, Pennsylvania 191075098, United States
Milton S Hershey Med Ctr, Hershey, Pennsylvania 170330850, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Med Univ of South Carolina, Charleston, South Carolina 294253312, United States
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
Univ Texas Health Science Ctr / Univ Texas Med School, Houston, Texas 77030, United States
Univ of Texas Galveston, Galveston, Texas 775550435, United States
Univ of Washington, Seattle, Washington 981224304, United States
Great Lakes Hemophilia Foundation, Wauwatosa, Wisconsin 532130127, United States
Reiter G, Wojnarowski C. Low rate of nelfinavir discontinuation in a clinic population. Int Conf AIDS. 1998;12:1049 (abstract no 60273)
[No authors listed] ACTG 320 trial halted as three-drug arm proves superior. AIDS Patient Care STDS. 1997 Jun;11(3):194. No abstract available.
[No authors listed] Conference updates show promising drug data. Aids Alert. 1997 Nov;12(11):125-6. No abstract available.
Baker R. 3-drug therapy reduces deaths and new AIDS-related illnesses by 50%. BETA. 1997 Mar;:3-4. No abstract available.
Demeter LM, Hughes MD, Coombs RW, Jackson JB, Grimes JM, Bosch RJ, Fiscus SA, Spector SA, Squires KE, Fischl MA, Hammer SM. Predictors of virologic and clinical outcomes in HIV-1-infected patients receiving concurrent treatment with indinavir, zidovudine, and lamivudine. AIDS Clinical Trials Group Protocol 320. Ann Intern Med. 2001 Dec 4;135(11):954-64.
Demeter LM, Bosch RJ, Coombs RW, Fiscus S, Bremer J, Johnson VA, Erice A, Jackson JB, Spector SA, Squires KM, Fischl MA, Hughes MD, Hammer SM. Detection of replication-competent human immunodeficiency virus type 1 (HIV-1) in cultures from patients with levels of HIV-1 RNA in plasma suppressed to less than 500 or 50 copies per milliliter. J Clin Microbiol. 2002 Jun;40(6):2089-94.
Coplan P, Cook J, Carides G, Nguyen BY, Testa M. Impact of indinavir with zidovudine and lamivudine on quality of life for HIV patients with < or = 200 CD4 in ACTG 320. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:86 (abstract no 101)
Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, Eron JJ Jr, Feinberg JE, Balfour HH Jr, Deyton LR, Chodakewitz JA, Fischl MA. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997 Sep 11;337(11):725-33.
Demeter LM, Degruttola V, Eshleman S, Jackson JB, Hughes M, Hammer SM. Baseline (BL) HIV-1 protease (PR) and reverse transcriptase (RT) genotype as a predictor of response to ZDV+3TC+indinavir (IDV). Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:92 (abstract no 131)
Freedberg KA, Goldie SJ, Paltiel AD, Losina E, Cohen CJ, Seage GR, Craven DE, Zhang H, Kimmel AD, Sullivan LM, Weinstein MC. Combination antiretroviral therapy is both effective and cost-effective. 39th Intersci Conf Antimicrob Agents Chemother. 1999 Sept 26-29 (abstract no I-2070)
Coplan PM, Cook JR, Carides GW, Heyse JF, Wu AW, Hammer SM, Nguyen BY, Meibohm AR, DiNubile MJ; AIDS Clinical Trials Group 320 Study Team. Impact of indinavir on the quality of life in patients with advanced HIV infection treated with zidovudine and lamivudine. Clin Infect Dis. 2004 Aug 1;39(3):426-33. Epub 2004 Jul 19.
