A Phase I/II Dosing Study of the Safety and Antiretroviral Activity of Hydroxyurea Alone and in Combination With ddI Compared With ddI Alone in Subjects With HIV Infection

Inclusion Criteria

Concurrent Medication:

Allowed:

AS PER AMENDMENT 5/5/97:

• PCP prophylaxis with trimethoprim/sulfamethoxazole or Dapsone.

Patients must have:

• HIV-1 infection.
• AS PER AMENDMENT 5/5/97:
• CD4 count of 200 - 700 cells/mm3 within 60 days prior to study entry.
• AS PER AMENDMENT 10/1/97:
• HIV RNA plasma level < 20,000 copies/ml within 60 days of enrollment (obtained at a laboratory certified to perform the Roche Monitor assay).

Exclusion Criteria

Co-existing Condition:

Patients with any of the following symptoms or conditions are excluded:

• CMV, MAC, toxoplasmosis, or disseminated fungal infection requiring acute or chronic therapy.
• Significant medical illness as determined by investigator.
• Active diagnosis of any malignancy, including visceral Kaposi's sarcoma or extensive cutaneous Kaposi's sarcoma for which systemic chemotherapy is anticipated within the next 24 weeks.
• Current Grade 2 or greater peripheral neuropathy.

Concurrent Medication:

Excluded:

• Acute or chronic therapy for CMV, MAC, toxoplasmosis, or disseminated fungal infection.

AS PER AMENDMENT 5/5/97:

• All antiretroviral medications other than those provided on study.
• Systemic chemotherapy for active malignancies, including systemic treatment for KS.
• Agents with myelosuppressive potential, including tegretol, carboplatin, carmustine, cyclophosphamide and fluorouracil.
• Granulocyte colony stimulating factor (G-CSF) except while hydroxyurea or matching placebo is held.

Drugs associated with peripheral neuropathy, including:

• hydralazine, disulfiram, nitrofurantoin, cisplatinum, diethyldithiocarbamate, gold, rifampin, chloramphenicol, clioquinol, ethambutol, ethionamide, glutethimide, sodium cyanate, and thalidomide.

Patients with any of the prior conditions are excluded:

• History of transfusion dependent anemia, defined as any history of repeated transfusion with two or more units of red blood cells.
• At the discretion of the investigator, history of pancreatitis.

Prior Medication:

Excluded:

• More than 2 weeks prior treatment with ddI.

AS PER AMENDMENT 5/5/97:

• Other antiretrovirals must be discontinued at least 14 days prior to randomization.
• Prior hydroxyurea.
• Any candidate HIV vaccine or agent with potential immune modulating effects within the past 30 days.
• Any colony stimulating factor or erythropoietin within the past 60 days.

Prior Treatment:

Excluded:

• Transfusion with red blood cells within the past 60 days.

Risk Behavior:

Excluded:

• At the investigator's discretion, any active substance abuse, including alcohol abuse interfering with compliance.

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety