To compare the efficacy and safety of orally administered didanosine (ddI) with orally administered zidovudine (AZT) in the treatment of patients who exhibit increasing clinical deterioration despite treatment with AZT.

Condition	Treatment or Intervention
HIV Infections	Drug: Zidovudine  Drug: Didanosine

Ages Eligible for Study:  12 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Allowed for Hematologic toxicity:

• Erythropoietin.
• Colony-Stimulating Factors.
• Allowed for prophylaxis of Pneumocystis carinii pneumonia (PCP):
• Aerosolized pentamidine.
• Trimethoprim/sulfamethoxazole.
• Dapsone.
• NOTE:
• If intravenous pentamidine is required for treatment of PCP, study drug should be suspended until one week after completion of intravenous pentamidine.
• Allowed:
• Prophylactic or suppressive therapy begun prior to study entry with the exception of neurotoxic agents (as defined in the protocol).

Concurrent Treatment: Allowed:

• Transfusions for hematologic toxicity.

Exclusion Criteria

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

• Active acute AIDS defining infection.
• Clinical evidence of acute pancreatitis in the last two years or chronic pancreatitis.
• Dementia of such severity that patient cannot give informed consent.
• Grade 2 or worse peripheral neuropathy as defined by Targeted Neuropathy Score (Schaumberg).
• Prior Cytomegalovirus disease requiring ongoing systemic ganciclovir therapy.
• Extensive Kaposi's sarcoma or other malignancy requiring systemic cytotoxic myelosuppressive or neurotoxic chemotherapy.
• Cardiomyopathy or the need for antiarrhythmic therapy.
• Inability to tolerate at least 600 mg per day of zidovudine (AZT).
• Seizures within the last 6 months or the need for anticonvulsant therapy.

Concurrent Medication: Excluded:

• Ganciclovir (DHPG).
• Myelosuppressive or neurotoxic chemotherapy.
• Antiarrhythmic therapy.
• Anticonvulsant therapy.
• Neurotoxic agents (as defined in the protocol).
• NOTE:
• If intravenous pentamidine is required for treatment of Pneumocystis carinii pneumonia (PCP), study drug should be suspended until 1 week after completion of intravenous pentamidine.

Patients with the following are excluded:

• Symptoms and conditions defined in the Patient Exclusion Co-Existing Conditions field.
• Average of two sequential CD4 counts from SciCor Clinical Laboratories in the 30 days prior to study entry > 300 cells/mm3.

Prior Medication: Excluded, participation in studies using:

• Dideoxyinosine (ddI).
• 2',3'-Dideoxy-2',3'-didehydrothymidine (d4T).
• Dideoxycytidine (ddC).
• Excluded within one month of study entry:
• Any other experimental antiretroviral compounds.

Patients must:

• Have documented HIV positivity via ELISA.
• Meet CDC criteria for AIDS or AIDS related complex (ARC).
• Have received zidovudine (AZT) for = or > 6 months and tolerated a dose of at least 500 mg per day without significant hematologic toxicity.
• Have no acute AIDS defining opportunistic infection, but may be receiving suppressive therapy for such infections.
• Demonstrate at least one of the following criteria for clinical deterioration despite AZT therapy within 4 weeks prior to study entry (8 weeks prior for weight loss):
• involuntary weight loss of more than 5 percent of the body weight occurring over the 8 week period prior to study entry, Karnofsky score = or > 50 but demonstrating a fall = or > 20 from previous level of functioning (assessment must be persistent on two occasions at least 14 days apart), unexplained fever of = or > 38 degrees C (despite evaluation defined in protocol) for more than 7 days, appearance of newly diagnosed oral hairy leukoplakia or oral candidiasis, or recurrence of a previously quiescent multidermatomal varicella-zoster, appearance of dermatologic afflictions (e.g. psoriasis, molluscum contagiosum, or newly diagnosed seborrheic dermatitis), appearance of chronic herpetic ulcers not responsive to acyclovir therapy. Required:
• Zidovudine (AZT) for = or > 6 months prior to study entry.

Arizona
      Univ of Arizona / Health Science Ctr, Tucson,  Arizona,  85724,  United States
Connecticut
      Yale Univ Med School, New Haven,  Connecticut,  06510,  United States
Florida
      G E Morey Jr, Fort Lauderdale,  Florida,  33316,  United States
      VP Med Services / HHCS Research Institute Inc, Orlando,  Florida,  32806,  United States
Georgia
      AIDS Research Consortium of Atlanta, Atlanta,  Georgia,  30308,  United States
Illinois
      Edward Hines Veterans Administration Hosp, Hines,  Illinois,  60141,  United States
Kansas
      Univ of Kansas School of Medicine, Wichita,  Kansas,  67214,  United States
Michigan
      Harper Hosp, Detroit,  Michigan,  48201,  United States
New York
      Albany Med College / AIDS Treatment Ctr, Albany,  New York,  12203,  United States
Ohio
      Med College of Ohio, Toledo,  Ohio,  43699,  United States
Pennsylvania
      Univ of Pennsylvania / HIV Clinic, Philadelphia,  Pennsylvania,  19104,  United States
Texas
      Univ of Texas Southwestern Med Ctr of Dallas, Dallas,  Texas,  75235,  United States
      Audie L Murphy Veterans Administration Hosp, San Antonio,  Texas,  78284,  United States
      Univ TX Galveston Med Branch, Galveston,  Texas,  775550882,  United States
Utah
      Univ of Utah School of Medicine, Salt Lake City,  Utah,  84132,  United States
Virginia
      Dr Stephen L Green, Hampton,  Virginia,  23666,  United States
Wisconsin
      Milwaukee County Med Complex, Milwaukee,  Wisconsin,  53226,  United States
Puerto Rico
      UPR School of Medicine, San Juan,  009275800,  Puerto Rico

Study ID Numbers:  039B; AI454-010
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00002035
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08