A Randomized, Double-Blind Phase II/III Trial of Monotherapy Vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3

Condition(s) targeted: HIV Infections

Intervention: Zidovudine (Drug); Zalcitabine (Drug); Didanosine (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Katzenstein D, Study Chair
Hammer S, Study Chair

To determine the efficacy and safety of zidovudine ( AZT ) versus didanosine ( ddI ), AZT plus ddI, and AZT plus zalcitabine ( ddC ) in preventing disease progression in HIV-infected patients with CD4 counts of 200-500 cells/mm3.

Official title: A Randomized, Double-Blind Phase II/III Trial of Monotherapy Vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3

Study design: Treatment, Double-Blind, Safety Study

Detailed description: Patients are randomized to receive AZT alone, AZT and ddI, AZT and ddC, or ddI alone for at least 2 years. Patients who develop AIDS or whose CD4 count falls to 50 percent or less of baseline are crossed over to another treatment arm.

PER AMENDMENT 4/5/95: Study treatment will be available until 10/31/95 at the latest for patients still taking study medications on 4/30/95, so that follow-up trials may be completed and approved.

Minimum age: 12 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria

Concurrent Medication:

Allowed:

- PCP prophylaxis, M. tuberculosis prophylaxis, short courses of acyclovir, chronic

suppressive acyclovir, pneumovax or Hib vaccine, antibiotics, rEPO and G-CSF for grade 3 or worse anemia and neutropenia, systemic corticosteroids for < 21 days, regularly prescribed medications, and vitamins or herbal therapies.

Patients must have:

- HIV infection without AIDS with CD4 200-500 cells/mm3.

PER AMENDMENT 4/5/95:

- Patients must have remained on ACTG 175 study treatment through 4/30/95 and meet

toxicity management criteria for continuing treatment. Subjects taking ACTG 175 crossover treatment are eligible.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions are excluded:

- Current AIDS-related condition other than minimal KS, grade 2 or worse peripheral

neuropathy, and malignancy requiring systemic therapy.

Concurrent Medication:

Excluded:

- Other anti-HIV drugs, biologic response modifiers other than rEPO and G-CSF, systemic

cytotoxic chemotherapy, chronic systemic corticosteroids, or any drug that affects AZT glucuronidation or clearance.

Concurrent Treatment:

Excluded:

- Radiotherapy other than limited local therapy to skin.

Patients with the following prior conditions are excluded:

- AIDS-related condition other than minimal KS; intolerance to AZT, ddI, or ddC at study

doses; and acute or chronic pancreatitis.

Prior Medication:

Excluded:

- Acute therapy for an infection or other medical illness within the past 14 days.

Current alcohol abuse.

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

UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla, California 920930672, United States

Sepulveda Veterans Adm Med Ctr / Olive View Med Ctr, Sylmar, California 91342, 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

Summitt Med Ctr / San Francisco Gen Hosp, Oakland, California 94609, 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

Univ of Washington / Children's Hosp of Los Angeles, Los Angeles, California 90027, United States

Huntington Memorial Hosp / Children's Hosp of Los Angeles, Pasadena, California 91105, United States

Children's Hosp of Los Angeles, Los Angeles, California 90027, United States

UCSD / Children's Hosp 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

Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium, San Jose, California 951282699, United States

Olive View Med Ctr, Sylmar, California 91342, United States

Univ Hosp / Univ of Colorado Health Sci Ctr, Denver, Colorado 80262, United States

Mountain States Reg Hemo Ctr / Univ of Colorado, Denver, Colorado 80262, United States

Mountain States Hemo Ctr / Univ of Utah, Denver, Colorado 80262, United States

Saint Joseph's Hosp & Med Ctr / Mtn States Reg Hemo Ctr, Denver, Colorado 80262, United States

Connecticut Children's Med Ctr, Farmington, Connecticut 060303805, United States

Yale Univ / New Haven, New Haven, Connecticut 065102483, United States

George Washington Univ Med Ctr, Washington, District of Columbia 20037, United States

Howard Univ, Washington, District of Columbia 20059, United States

Georgetown Univ Med Ctr, Washington, District of Columbia 20007, United States

HIV Ctr - District of Columbia Gen Hosp, Washington, District of Columbia 200072197, United States

George Washington Univ / Hershey Med Ctr, Washington, District of Columbia 20037, United States

Univ of Miami School of Medicine, Miami, Florida 331361013, United States

Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr, Atlanta, Georgia 303652225, United States

Univ of Hawaii, Honolulu, Hawaii 96816, United States

Children's Mem Hosp Family Cln / Northwestern Univ Med Schl, Chicago, Illinois 60611, United States

Northwestern Univ Med School, Chicago, Illinois 60611, United States

Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States

Cook County Hosp, Chicago, Illinois 60612, United States

Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States

Indiana Univ / Riley Hosp for Children, Indianapolis, Indiana 46202, United States

Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States

Great Plains - Hemophilia / Univ of Iowa Hosp & Clinic, Iowa City, Iowa 52242, United States

Univ of Iowa Hosp and Clinic, Iowa City, Iowa 52242, United States

Univ of Louisville / East Tennesee Comprehensive Hem Ctr, Louisville, Kentucky 40202, 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

Tulane Univ / Charity Hosp of New Orleans, New Orleans, Louisiana 701122699, 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 Med Ctr, Boston, Massachusetts 02215, United States

Beth Israel Deaconess - West Campus, Boston, Massachusetts 02215, United States

Boston Med Ctr, Boston, Massachusetts 02118, United States

Children's Hosp of Boston, Boston, Massachusetts 021155724, United States

Boston City Hosp / Pediatrics, Boston, Massachusetts 02118, United States

Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States

Univ of Massachusetts Med Ctr, Worcester, Massachusetts 01655, United States

Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial, Worcester, Massachusetts 01605, United States

Rhode Island Hemophilia Ctr / Med Ctr of Cntrl MA, Worcester, Massachusetts 01605, United States

Brigham and Women's Hosp, Boston, Massachusetts 02115, United States

Children's Hosp of Michigan, Detroit, Michigan 48201, United States

Michigan State Univ Hemophilia Comprehensive Care Clinic, Lansing, Michigan 48912, United States

Univ of Minnesota, Minneapolis, Minnesota 55455, United States

St Paul Ramsey Med Ctr, St. Paul, Minnesota 55101, United States

St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States

Nebraska Regional Hemophilia Ctr / Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States

St Louis Univ Med Ctr / Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States

Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States

Dartmouth - Hitchcock Med Ctr / Med Ctr Cntrl Massachusetts, Lebanon, New Hampshire 03756, United States

Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark, New Jersey 071032714, United States

Robert Wood Johnson Med School / Hershey Med Ctr, New Brunswick, New Jersey 08903, United States

UMDNJ - New Jersey Med School, Newark, New Jersey 07107, United States

Montefiore Drug Treatment Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States

Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States

Samaritan Village Inc / Bronx Municipal Hosp, Bronx, New York 10461, United States

Nassau County Med Ctr, East Meadow, New York 11554, United States

SUNY / State Univ of New York, Syracuse, New York 13210, United States

SUNY - Stony Brook, Stony Brook, New York 117948153, 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

Mount Sinai Med Ctr, New York, New York 10029, United States

Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States

Cornell Univ Med Ctr, New York, New York 10021, United States

Saint Luke's - Roosevelt Hosp Ctr, New York, New York 10025, United States

Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States

Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, 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

City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst, New York 11373, United States

Puerto Genetic Disease Clinic, New York, New York 10029, United States

Montefiore Med Ctr Adolescent AIDS Program, Bronx, New York 10467, United States

SUNY / Health Sciences Ctr at Brooklyn, Brooklyn, New York 112032098, United States

Saint Clare's Hosp and Health Ctr, New York, New York 10019, United States

North Shore Univ Hosp, Manhasset, New York 11030, United States

North Central Bronx Hosp / Bronx Municipal Hosp, Bronx, New York 10467, United States

Wake Med Ctr / Univ of North Carolina, Chapel Hill, North Carolina 275997215, 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

Wake County Dept of Health, Raleigh, North Carolina 27610, United States

Glaxo Wellcome Inc, Research Triangle Park, North Carolina 27709, 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

Med College of Ohio, Toledo, Ohio 43699, United States

Northwest Ohio Hemo Treatment Ctr / Great Lakes Hemo Fdn, Toledo, Ohio 43606, United States

Oregon Health Sciences Univ / Children's Hosp of Los Angeles, Portland, Oregon 97201, United States

Milton S Hershey Med Ctr, Hershey, Pennsylvania 170330850, United States

Hemophilia Ctr of Western PA / Univ of Pittsburgh, Pittsburgh, Pennsylvania 15219, United States

Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States

Univ of Pittsburgh Med School / Hershey Med Ctr, Hershey, Pennsylvania 170330850, United States

Thomas Jefferson Univ Hosp, Philadelphia, Pennsylvania 191075098, United States

Julio Arroyo, West Columbia, South Carolina 29169, United States

Med Univ of South Carolina / UNC, Charleston, South Carolina 29425, United States

Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr, Knoxville, Tennessee 37920, United States

Univ Texas Health Science Ctr / Univ Texas Med School, Houston, Texas 77030, United States

Univ of Texas Southwestern Med Ctr of Dallas, Dallas, Texas 75235, 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

Northern Wisconsin Hemophilia Ctr / Saint Vincent's Hosp, Green Bay, Wisconsin 54301, United States

Comp Hemo Ctr of Ctrl & N Illinois / Great Lakes Hemo Fdn, Wauwatosa, Wisconsin 532130127, United States

Youngstown Hemophilia Ctr / Great Lakes Hemophilia Fdn, Wauwatosa, Wisconsin 53213, United States

Click here for more information about Zidovudine

Click here for more information about Zalcitabine

Click here for more information about Didanosine

Related publications:

Havlir DV, Richman DD. Viral dynamics of HIV: implications for drug development and therapeutic strategies. Ann Intern Med. 1996 Jun 1;124(11):984-94. Review.

Hammer SM, Katzenstein DA, Hughes MD, Gundacker H, Schooley RT, Haubrich RH, Henry WK, Lederman MM, Phair JP, Niu M, Hirsch MS, Merigan TC. A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter. AIDS Clinical Trials Group Study 175 Study Team. N Engl J Med. 1996 Oct 10;335(15):1081-90.

Simpson DM, Katzenstein DA, Hughes MD, Hammer SM, Williamson DL, Jiang Q, Pi JT. Neuromuscular function in HIV infection: analysis of a placebo-controlled combination antiretroviral trial. AIDS Clinical Group 175/801 Study Team. AIDS. 1998 Dec 24;12(18):2425-32.

[No authors listed] Zidovudine, didanosine, and zalcitabine in the treatment of HIV infection: meta-analyses of the randomised evidence. HIV Trialists' Collaborative Group. Lancet. 1999 Jun 12;353(9169):2014-25.

Katzenstein DA, Hughes MD, Albrecht M, Liou SH, Murphy R, Balfour H, Para M, Hammer S. Virologic and CD4 cell response to zidovudine or zidovudine and lamivudine following didanosine treatment of human immunodeficiency virus infection. AIDS Res Hum Retroviruses. 2001 Feb 10;17(3):203-10.

Justice AC, Holmes W, Gifford AL, Rabeneck L, Zackin R, Sinclair G, Weissman S, Neidig J, Marcus C, Chesney M, Cohn SE, Wu AW. Development and validation of a self-completed HIV symptom index. J Clin Epidemiol. 2001 Dec;54 Suppl 1:S77-90.

Katzenstein DA, Hammer SM, Hughes MD, Gundacker H, Jackson JB, Fiscus S, Rasheed S, Elbeik T, Reichman R, Japour A, Merigan TC, Hirsch MS. The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. AIDS Clinical Trials Group Study 175 Virology Study Team. N Engl J Med. 1996 Oct 10;335(15):1091-8.

Fiscus SA, Hughes MD, Lathey JL, Pi T, Jackson B, Rasheed S, Elbeik T, Reichman R, Japour A, Byington R, Scott W, Griffith BP, Katzenstein DA, Hammer SM. Changes in virologic markers as predictors of CD4 cell decline and progression of disease in human immunodeficiency virus type 1-infected adults treated with nucleosides. AIDS Clinical Trials Group Protocol 175 Team. J Infect Dis. 1998 Mar;177(3):625-33.

Currier JS, Spino C, Grimes J, Wofsy CB, Katzenstein DA, Hughes MD, Hammer SM, Cotton DJ. Differences between women and men in adverse events and CD4+ responses to nucleoside analogue therapy for HIV infection. The Aids Clinical Trials Group 175 Team. J Acquir Immune Defic Syndr. 2000 Aug 1;24(4):316-24.

Kastrissios H, Suarez JR, Katzenstein D, Girard P, Sheiner LB, Blaschke TF. Characterizing patterns of drug-taking behavior with a multiple drug regimen in an AIDS clinical trial. AIDS. 1998 Dec 3;12(17):2295-303.

Lathey JL, Hughes MD, Fiscus SA, Pi T, Jackson JB, Rasheed S, Elbeik T, Reichman R, Japour A, D'Aquila RT, Scott W, Griffith BP, Hammer SM, Katzenstein DA. Variability and prognostic values of virologic and CD4 cell measures in human immunodeficiency virus type 1-infected patients with 200-500 CD4 cells/mm(3) (ACTG 175). AIDS Clinical Trials Group Protocol 175 Team. J Infect Dis. 1998 Mar;177(3):617-24.

Last updated: June 23, 2005