To determine the relative clinical efficacy of zidovudine ( AZT ) plus didanosine (ddI), AZT plus zalcitabine ( ddC ), AZT alternating monthly with ddI, and AZT/ddI plus nevirapine in HIV-infected patients with advanced disease. The rapid emergence of resistant HIV strains has been observed in patients receiving monotherapy with a nucleoside analog or non-nucleoside reverse transcriptase inhibitor. Use of combination therapy with two nucleoside drugs or convergent combination therapy with two nucleosides and a non-nucleoside RT inhibitor may minimize the evolution of these resistant HIV strains. Since toxicity is a major problem in patients with advanced disease who are receiving combination nucleoside therapy, alternating the two drugs may provide a way of retaining several benefits of combination therapy while minimizing the increased toxicity.

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

Further Study Details: 

Expected Total Enrollment:  1292

The rapid emergence of resistant HIV strains has been observed in patients receiving monotherapy with a nucleoside analog or non-nucleoside reverse transcriptase inhibitor. Use of combination therapy with two nucleoside drugs or convergent combination therapy with two nucleosides and a non-nucleoside RT inhibitor may minimize the evolution of these resistant HIV strains. Since toxicity is a major problem in patients with advanced disease who are receiving combination nucleoside therapy, alternating the two drugs may provide a way of retaining several benefits of combination therapy while minimizing the increased toxicity.

Patients are randomized to receive either AZT/ddC, AZT/ddI, AZT alternating monthly with ddI, or AZT/ddI/nevirapine. Patients are evaluated at week 0 and every 4 weeks thereafter for 2 years. Pharmacologic, virologic, and macroneurologic substudies will be conducted. Patients who are already enrolled on protocol ACTG 193 will be given the option of continuing on their originally assigned ACTG 193 therapy for an additional 6 months or undergoing re-randomization to one of the four treatment arms on ACTG 193A.

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

Criteria

Inclusion Criteria

Concurrent Medication: Required:

• PCP prophylaxis.

Allowed:

• Erythropoietin maintenance.
• G-CSF and GM-CSF.
• Prophylaxis for Mycobacterium avium intracellulare.
• Antifungal prophylaxis or treatment with specific drugs.
• Maintenance therapy for opportunistic infection.
• Over-the-counter medications or alternative therapies such as vitamins and herbs.
• Antibiotics as clinically indicated.
• Steroids for < 21 days for acute problems.
• Antipyretics, analgesics, allergy medication, antidepressants, sleep medications, oral contraceptives, or other appropriate medications.

Concurrent Treatment: Allowed:

• Radiation therapy for cutaneous Kaposi's sarcoma.
• Acupuncture.

Patients must have:

• Documented HIV infection.
• CD4 count <= 50 cells/mm3.
• Either no prior nucleoside therapy OR a history of prior nucleoside therapy in the absence of high-grade intolerance.
• Life expectancy of at least 6 months.
• Consent of parent or guardian if < 18 years of age.
• Normal chest x-ray at baseline or within 6 months prior to study entry in the absence of new pulmonary or cardiac symptoms (per 12/28/94 amendment).

NOTE:

• Patients who withdrew from protocol ACTG 193 therapy prior to activation of ACTG 193A are not eligible.

Exclusion Criteria

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

• Abnormal baseline chest x-ray.
• New pulmonary or cardiac symptoms.
• Psychological or emotional problems sufficient to prevent compliance with study medication.

Concurrent Medication: Excluded:

• Systemic chemotherapy for malignancy.
• Acute or induction therapy for opportunistic infection.
• Antiretroviral drugs other than study drugs.
• Biological response modifiers.
• Erythromycin, phenytoin, phenobarbital, warfarin, or coumadin.

Patients with the following prior conditions are excluded:

• History of recurrent grade 3 or greater toxicity to AZT, ddI, or ddC on two or more occasions.
• Evidence of active pulmonary disease within 6 months prior to study entry.
• History of grade 3 or worse peripheral neuropathy.
• History of acute or chronic pancreatitis.

Prior Medication: Excluded:

• Prior nevirapine.

Excluded within 7 days prior to study entry:

• Acute therapy for opportunistic infection (maintenance therapy is permitted).
• Acute systemic therapy for a nonopportunistic infection or other medical condition.
• Antiretroviral drugs other than AZT, ddI, or ddC.
• Biological response modifiers.
• d4T therapy.
• Nucleosides other than those used in the study.
• Antibiotics containing clavulanate potassium.

Prior Treatment: Excluded:

• More than 4 units of blood in a 30-day period.

Active alcohol or drug abuse.

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  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
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  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
      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
Colorado
      Mountain States Reg Hemo Ctr / Univ of Colorado, Denver,  Colorado,  80262,  United States
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
      Denver Dept of Health and Hosps, Denver,  Colorado,  80262,  United States
      Rose Med Ctr, Denver,  Colorado,  80262,  United States
Connecticut
      Yale Univ / New Haven, New Haven,  Connecticut,  065102483,  United States
District of Columbia
      Howard Univ, Washington,  District of Columbia,  20059,  United States
      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
      George Washington Univ / Hershey Med Ctr, Washington,  District of Columbia,  20037,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
      Univ of South Florida, Tampa,  Florida,  33612,  United States
Hawaii
      Univ of Hawaii, Honolulu,  Hawaii,  96816,  United States
Illinois
      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
      Louis A Weiss Memorial Hosp, Chicago,  Illinois,  60640,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
      Methodist Hosp of Indiana / Life Care Clinic, Indianapolis,  Indiana,  46202,  United States
Kentucky
      Univ of Louisville / East Tennesee Comprehensive Hem Ctr, Louisville,  Kentucky,  40202,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States
      Boston Med Ctr, Boston,  Massachusetts,  02118,  United States
      Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial, Worcester,  Massachusetts,  01605,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States
      St Paul Ramsey Med Ctr, St. Paul,  Minnesota,  55101,  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 Hampshire
      Dartmouth - Hitchcock Med Ctr / Med Ctr Cntrl Massachusetts, Lebanon,  New Hampshire,  03756,  United States
New Jersey
      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
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
      SUNY / State Univ of New York, Syracuse,  New York,  13210,  United States
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  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
      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
      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
      Comprehensive Health Care Ctr / Bronx Municipal Hosp, Bronx,  New York,  10461,  United States
      Columbia Presbyterian Med Ctr, New York,  New York,  100323784,  United States
      Adirondack Med Ctr at Saranac Lake, Albany,  New York,  122083479,  United States
      Mid - Hudson Care Ctr, Albany,  New York,  122083479,  United States
      Albany Med College / Division of HIV Medicine A158, Albany,  New York,  122083479,  United States
      Harlem Hosp Ctr, New York,  New York,  10037,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
      Moses H Cone Memorial Hosp, Greensboro,  North Carolina,  27401,  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
      MetroHealth Med Ctr, Cleveland,  Ohio,  441091998,  United States
      Univ of Kentucky Lexington, Cincinnati,  Ohio,  45267,  United States
Pennsylvania
      Univ of Pennsylvania at Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Thomas Jefferson Univ Hosp, Philadelphia,  Pennsylvania,  191075098,  United States
      Girard Med Ctr, Philadelphia,  Pennsylvania,  191046073,  United States
      Milton S Hershey Med Ctr, Hershey,  Pennsylvania,  170330850,  United States
      Saint Michael's Med Ctr / Milton S Hershey Med Ctr, Hershey,  Pennsylvania,  170330850,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
      Med Univ of South Carolina / UNC, Charleston,  South Carolina,  29425,  United States
Tennessee
      Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr, Knoxville,  Tennessee,  37920,  United States
      Meharry Med College, Nashville,  Tennessee,  37203,  United States
Texas
      Univ Texas Health Science Ctr / Univ Texas Med School, Houston,  Texas,  77030,  United States
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States
Washington
      Univ of Washington, Seattle,  Washington,  981224304,  United States
Wisconsin
      Great Lakes Hemophilia Foundation, Wauwatosa,  Wisconsin,  532130127,  United States
      Northern Wisconsin Hemophilia Ctr / Saint Vincent's Hosp, Green Bay,  Wisconsin,  54301,  United States
Puerto Rico
      Univ of Puerto Rico, San Juan,  009365067,  Puerto Rico

Study chairs or principal investigators

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

Study ID Numbers:  ACTG 193A
Record last reviewed:  October 1996
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000781
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08