To determine the relationship of viral susceptibility to zidovudine (AZT) and baseline viral load (as determined by plasma viremia and quantitative endpoint dilution). To determine the relationship between viral load and susceptibility during different antiretroviral therapy strategies. To correlate measures of viral load and short term clinical and laboratory markers (such as weight, CD4 count, p24 antigenemia, and beta2 microglobulin) on the different therapy arms. High-grade resistance to AZT has been detected in HIV isolates from approximately 25 percent of individuals with AIDS who received AZT for at least 1 year. To elucidate the clinical significance of in vitro AZT resistance, it is necessary to distinguish between clinical failure caused by AZT resistance and clinical decompensation caused by other factors.

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

Further Study Details: 

Expected Total Enrollment:  120

High-grade resistance to AZT has been detected in HIV isolates from approximately 25 percent of individuals with AIDS who received AZT for at least 1 year. To elucidate the clinical significance of in vitro AZT resistance, it is necessary to distinguish between clinical failure caused by AZT resistance and clinical decompensation caused by other factors.

One hundred-twenty patients who have been receiving AZT for at least 1 year are randomized to 1) continue with AZT, 2) switch to treatment with didanosine at 1 of 2 doses, or 3) receive both AZT and ddI. Treatment is given for 16 weeks, with a possible extension to 32 weeks. Patients are followed at weeks 2, 4, 8, 12, and 16. For analysis purposes only, patients are stratified according to degree of susceptibility of HIV isolates to AZT.

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

Criteria

Inclusion Criteria

Concurrent Medication: Allowed:

• Chemoprophylaxis against Pneumocystis carinii pneumonia (PCP), Mycobacterium tuberculosis, or Herpes simplex virus, or against other opportunistic infections as indicated.
• Corticosteroids for no longer than 21 days (only as part of PCP therapy).
• Erythropoietin and G-CSF.

Patients must have:

• Documented HIV-seropositivity.
• CD4 count 100 - 300 cells/mm3.
• Prior continuous AZT dose = or > 300 mg/day for 1 year or longer.

Prior Medication: Required:

• AZT for at least 1 year prior to study entry.

Exclusion Criteria

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

• Medical contraindication or is considered noncompliant in the opinion of the investigator.
• Peripheral neuropathy = or > grade 2.

Concurrent Medication: Excluded:

• Anti-HIV agents other than study drugs.
• Biologic response modifiers (other than erythropoietin or G-CSF).
• Systemic cytotoxic chemotherapy.
• Regularly prescribed medications (such as antipyretics, analgesics, allergy medications) that are associated with an increased risk of pancreatitis, peripheral neuropathy, or bone marrow suppression.

Concurrent Treatment: Excluded:

• Radiation therapy.

Patients with the following prior conditions are excluded:

• History of acute or chronic pancreatitis, gout, or uric acid nephropathy.

Prior Medication: Excluded:

• Other antiretrovirals besides AZT.
• ddI or ddC for more than 30 days within the past year or any time within 3 months prior to study entry.
• Acute therapy for an infection or other medical illness within 14 days prior to study entry.

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
California
      San Francisco Gen Hosp, San Francisco,  California,  941102859,  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
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
      Kaiser Permanente Franklin Med Ctr, Denver,  Colorado,  80262,  United States
Illinois
      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
Massachusetts
      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States
Nebraska
      Univ of Nebraska Med Ctr, Omaha,  Nebraska,  681985130,  United States
New York
      SUNY / State Univ of New York, Syracuse,  New York,  13210,  United States
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      SUNY / Health Sciences Ctr at Brooklyn, Brooklyn,  New York,  112032098,  United States
Washington
      Univ of Washington, Seattle,  Washington,  981224304,  United States

Study chairs or principal investigators

Corey L,  Study Chair
Cavert W,  Study Chair
Coombs R,  Study Chair

Study ID Numbers:  ACTG 194
Record last reviewed:  July 1995
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00001025
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08