A Comparison of Three Treatments for Advanced HIV Disease in Patients Who Have Received Nucleoside Therapy in the Past

Condition(s) targeted: HIV Infections

Intervention: Zidovudine (Drug); Zalcitabine (Drug); Didanosine (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
WK Henry, Study Chair
JO Kahn, Study Chair
HH Balfour, Study Chair

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.

Official title: A Randomized, Double-Blind, Three-Arm Study Comparing Combination to Monthly Alternating Nucleoside Therapy for the Treatment of Advanced HIV Disease (CD4 <= 50/mm3) With a Prior History of Nucleoside Therapy

Study design: Treatment

Detailed description: 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.

Minimum age: 13 Years. Maximum age: N/A. Gender(s): 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.

Univ of Puerto Rico, San Juan 009365067, Puerto Rico

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

Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States

Yale Univ / New Haven, New Haven, Connecticut 065102483, 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

Univ of Hawaii, Honolulu, Hawaii 96816, United States

Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States

Cook County Hosp, Chicago, Illinois 60612, United States

Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States

Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States

Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States

Boston Med Ctr, Boston, Massachusetts 02118, United States

Univ of Minnesota, Minneapolis, Minnesota 55455, United States

Hennepin County Med Clinic, Minneapolis, Minnesota 55415, United States

St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States

Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States

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

Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States

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

Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States

Thomas Jefferson Univ Hosp, Philadelphia, Pennsylvania 191075098, United States

Julio Arroyo, West Columbia, South Carolina 29169, United States

Univ of Texas Galveston, Galveston, Texas 775550435, United States

Univ of Washington, Seattle, Washington 981224304, United States

Click here for more information about Zidovudine

Click here for more information about Zalcitabine

Click here for more information about Didanosine

Related publications:

Fichtenbaum CJ, Powderly WG. Refractory mucosal candidiasis in patients with human immunodeficiency virus infection. Clin Infect Dis. 1998 Mar;26(3):556-65. Review.

Henry K, Tierney C, Kahn J, Balfour H, Jiang Q, Kmack A, Fischl M. A randomized, double-blind, placebo-controlled study comparing combination nucleoside and triple therapy for the treatment of advanced HIV disease (CD4 less than or equal to 50/mm(3)). Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:207 (abstract no LB6)

Henry K, Erice A, Tierney C, Balfour HH Jr, Fischl MA, Kmack A, Liou SH, Kenton A, Hirsch MS, Phair J, Martinez A, Kahn JO. A randomized, controlled, double-blind study comparing the survival benefit of four different reverse transcriptase inhibitor therapies (three-drug, two-drug, and alternating drug) for the treatment of advanced AIDS. AIDS Clinical Trial Group 193A Study Team. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Dec 1;19(4):339-49.

Last updated: June 23, 2005