To compare the efficacy, safety and tolerance, and other clinical and immunologic effects of zidovudine (AZT) plus zalcitabine (dideoxycytidine; ddC), AZT plus didanosine (ddI), and AZT alternating monthly with ddI as measured by differences in survival among HIV-infected persons who have received 6 or more months of nucleoside monotherapy and have a CD4 count greater than or equal to 50 cells/mm3. Combining two nucleoside drugs has the theoretical advantage of optimal protection against the evolution of resistant strains of HIV. However, one major problem with combination nucleoside therapy in patients with advanced disease is the increased toxicity resulting from such therapy. One approach to minimize toxicity while perhaps retaining some of the benefits of combination therapy is to alternate the two drugs.

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

Further Study Details: 

Expected Total Enrollment:  654

Combining two nucleoside drugs has the theoretical advantage of optimal protection against the evolution of resistant strains of HIV. However, one major problem with combination nucleoside therapy in patients with advanced disease is the increased toxicity resulting from such therapy. One approach to minimize toxicity while perhaps retaining some of the benefits of combination therapy is to alternate the two drugs.

Patients are randomized to one of three treatment arms: AZT plus ddI, AZT plus ddC, and AZT alone alternating monthly with ddI. Half of the patients receiving AZT alternating monthly with ddI will start with AZT, while the other half will start with ddI. Treatment continues until death or termination of the study. Patients are followed every 4 weeks. The study will include a subset of patients for whom virologic, pharmacokinetic, and macroneurologic assessments will be made.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Required:

• PCP prophylaxis.

Allowed:

• Erythropoietin.
• Prophylaxis for MAI or fungal infections.
• Antibiotics.
• Over-the-counter, alternative, or regularly prescribed drugs.
• Steroids, if for < 21 days.

Concurrent Treatment: Allowed:

• Radiation therapy for cutaneous Kaposi's sarcoma.

Patients must have:

• HIV infection.
• CD4 count <= 50 cells/mm3.
• Prior nucleoside monotherapy for at least 6 months.
• Life expectancy of at least 6 months.

Prior Medication: Required:

• Nucleoside monotherapy for at least 6 months. Active alcohol or drug abuse.

Exclusion Criteria

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

• Severe peripheral neuropathy.
• Psychological or emotional problems sufficient to prevent study compliance.

Concurrent Medication: Excluded:

• Systemic chemotherapy for malignancy.
• Acute or induction therapy for opportunistic infection.

Patients with the following prior conditions are excluded:

• History of acute or chronic pancreatitis.
• Grade 3 or greater toxicity to AZT, ddI, or ddC on two or more occasions.

Prior Medication: Excluded:

• Non-study nucleosides or biologic response modifiers within 7 days prior to study entry.
• Acute therapy for opportunistic process within 14 days prior to study entry.
• Acute systemic therapy for other medical conditions within 14 days prior to study entry.

California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  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,  94110,  United States
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States
      Harbor UCLA Med Ctr, Torrance,  California,  90502,  United States
      Olive View Med Ctr, Sylmar,  California,  91342,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
Connecticut
      Yale Univ / New Haven, New Haven,  Connecticut,  065102483,  United States
District of Columbia
      Georgetown Univ Med Ctr, Washington,  District of Columbia,  20007,  United States
      Whitman - Walker Clinic / Georgetown Univ Med Ctr, Washington,  District of Columbia,  200072197,  United States
      HIV Ctr - District of Columbia Gen Hosp, Washington,  District of Columbia,  200072197,  United States
Hawaii
      Univ of Hawaii, Honolulu,  Hawaii,  96816,  United States
Illinois
      Rush Presbyterian - Saint Luke's Med Ctr, Chicago,  Illinois,  60612,  United States
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
      Methodist Hosp of Indiana / Life Care Clinic, Indianapolis,  Indiana,  46202,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
      Boston Med Ctr, Boston,  Massachusetts,  02118,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States
      Hennepin County Med Clinic, Minneapolis,  Minnesota,  55415,  United States
Missouri
      St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis,  Missouri,  63112,  United States
Nebraska
      Univ of Nebraska Med Ctr, Omaha,  Nebraska,  681985130,  United States
New York
      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
      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
      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
      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
      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  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
      Montefiore Med Ctr Adolescent AIDS Program, Bronx,  New York,  10467,  United States
      SUNY / Health Sciences Ctr at Brooklyn, Brooklyn,  New York,  112032098,  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
      Comprehensive Health Care Ctr / Bronx Municipal Hosp, Bronx,  New York,  10461,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
Ohio
      Case Western Reserve Univ, Cleveland,  Ohio,  44106,  United States
      Univ of Cincinnati, Cincinnati,  Ohio,  452670405,  United States
      Columbus Children's Hosp, Columbus,  Ohio,  432052696,  United States
      Med College of Ohio, Toledo,  Ohio,  43699,  United States
Pennsylvania
      Univ of Pennsylvania at Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Thomas Jefferson Univ Hosp, Philadelphia,  Pennsylvania,  191075098,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Texas
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States
Washington
      Univ of Washington, Seattle,  Washington,  981224304,  United States
Puerto Rico
      Univ of Puerto Rico, San Juan,  009365067,  Puerto Rico

Study chairs or principal investigators

WK Henry,  Study Chair
JO Kahn,  Study Chair
HH Balfour,  Study Chair

Study ID Numbers:  ACTG 193
Record last reviewed:  January 1995
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00001029
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08