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

NCT00000625 | Completed Phase 2

• 2 other identifiers: ACTG 17511150
• Study Type: interventional
• Target: 2,100
• Locations: 3 countries
• Sites: 58

Brief Summary

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.

Conditions

HIV Infections

Keywords

Zalcitabine; Didanosine; Drug Therapy, Combination; AIDS-Related Complex; Antiviral Agents; Zidovudine

Interventions

Zidovudine DRUG

Zalcitabine DRUG

Didanosine DRUG

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Bristol-Myers Squibb: collaborator
• Glaxo Wellcome: collaborator

Study Sites (58)

Alabama Therapeutics CRS

Birmingham, Alabama, 35294, United States

Location

USC CRS

Los Angeles, California, 90033, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90095, United States

Location

Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.

Oakland, California, 94609, United States

Location

Stanford CRS

Palo Alto, California, 94305, United States

Location

UCSD Maternal, Child, and Adolescent HIV CRS

San Diego, California, 92093, United States

Location

Ucsd, Avrc Crs

San Diego, California, United States

Location

Ucsf Aids Crs

San Francisco, California, United States

Location

Santa Clara Valley Med. Ctr.

San Jose, California, 95128, United States

Location

San Mateo County AIDS Program

San Mateo, California, 94305, United States

Location

Harbor-UCLA Med. Ctr. CRS

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80262, United States

Location

Howard University Hosp., Div. of Infectious Diseases, ACTU

Washington D.C., District of Columbia, 20059, United States

Location

Univ. of Miami AIDS CRS

Miami, Florida, 33136, United States

Location

Emory Univ. Hemophilia Program Office

Atlanta, Georgia, 30365, United States

Location

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, 96816, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Cook County Hosp. CORE Ctr.

Chicago, Illinois, 60612, United States

Location

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, 60612, United States

Location

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, 46202, United States

Location

Methodist Hosp. of Indiana

Indianapolis, Indiana, 46202, United States

Location

Univ. of Iowa Healthcare, Div. of Infectious Diseases

Iowa City, Iowa, 52242, United States

Location

Tulane Hemophilia Treatment Ctr.

New Orleans, Louisiana, 70112, United States

Location

Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU

New Orleans, Louisiana, 70112, United States

Location

Tulane/LSU Maternal/Child CRS

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hosp., Div. of Infectious Disease

Boston, Massachusetts, 02115, United States

Location

HMS - Children's Hosp. Boston, Div. of Infectious Diseases

Boston, Massachusetts, 02115, United States

Location

Bmc Actg Crs

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, 02215, United States

Location

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, 02215, United States

Location

Hennepin County Med. Ctr., Div. of Infectious Diseases

Minneapolis, Minnesota, 55455, United States

Location

University of Minnesota, ACTU

Minneapolis, Minnesota, United States

Location

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, 63112, United States

Location

Washington U CRS

St Louis, Missouri, United States

Location

Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.

Omaha, Nebraska, United States

Location

NJ Med. School CRS

Newark, New Jersey, United States

Location

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, 14215, United States

Location

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, 10003, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Cornell University A2201

New York, New York, 10021, United States

Location

Memorial Sloan-Kettering Cancer Ctr.

New York, New York, 10021, United States

Location

NYU Med. Ctr., Dept. of Medicine

New York, New York, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas HealthCare System, Carolinas Med. Ctr.

Charlotte, North Carolina, 28203, United States

Location

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, 27710, United States

Location

Regional Center for Infectious Disease, Wendover Medical Center CRS

Greensboro, North Carolina, 27401, United States

Location

Wake County Health and Human Services CRS

Raleigh, North Carolina, 27610, United States

Location

Univ. of Cincinnati CRS

Cincinnati, Ohio, 45267, United States

Location

Case CRS

Cleveland, Ohio, 44106, United States

Location

MetroHealth CRS

Cleveland, Ohio, United States

Location

The Ohio State Univ. AIDS CRS

Columbus, Ohio, 43210, United States

Location

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, 19104, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98122, United States

Location

Puerto Rico-AIDS CRS

San Juan, Puerto Rico

Location

Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

Mbeya, Tanzania

Location

Related Publications (11)

• 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. doi: 10.7326/0003-4819-124-11-199606010-00006.

  PMID: 8624066 BACKGROUND

• 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. doi: 10.1056/NEJM199610103351501.

  PMID: 8813038 BACKGROUND

• 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. doi: 10.1097/00002030-199818000-00011.

  PMID: 9875580 BACKGROUND

• 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.

  PMID: 10376616 BACKGROUND

• Katzenstein DA, Hughes MD, Albrecht M, Liou SH, Murphy R, Balfour H, Para M, Hammer S; ACTG 302 Study Team. 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. doi: 10.1089/088922201750063115.

  PMID: 11177402 BACKGROUND

• Justice AC, Holmes W, Gifford AL, Rabeneck L, Zackin R, Sinclair G, Weissman S, Neidig J, Marcus C, Chesney M, Cohn SE, Wu AW; Adult AIDS Clinical Trials Unit Outcomes Committee. Development and validation of a self-completed HIV symptom index. J Clin Epidemiol. 2001 Dec;54 Suppl 1:S77-90. doi: 10.1016/s0895-4356(01)00449-8.

  PMID: 11750213 BACKGROUND

• 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. doi: 10.1056/NEJM199610103351502.

  PMID: 8813039 BACKGROUND

• 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. doi: 10.1086/514248.

  PMID: 9498441 BACKGROUND

• 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. doi: 10.1097/00126334-200008010-00003.

  PMID: 11015147 BACKGROUND

• 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. doi: 10.1097/00002030-199817000-00011.

  PMID: 9863872 BACKGROUND

• 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. doi: 10.1086/514250.

  PMID: 9498440 BACKGROUND

MeSH Terms

Conditions

HIV Infections; AIDS-Related Complex

Interventions

Zidovudine; Zalcitabine; Didanosine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine; Cytidine; Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ribonucleosides

Study Officials

• Katzenstein D

  STUDY CHAIR

• Hammer S

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: DOUBLE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: November 1, 1995
• Last Updated: November 2, 2021

Record last verified: 2021-10

Locations

TA (1); US (56); PR (1)