A Randomized Trial of Three Anti-Pneumocystis Agents Plus Zidovudine for the Primary Prevention of Serious Infections in Patients With Advanced HIV Infection

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antifolate medication required to treat an intercurrent infection.
• Treatment of intercurrent infections or malignancies.
• Fluconazole.
• Itraconazole.
• Standard or investigational therapy for pneumocystosis (PCP) or toxoplasmosis.
• Only the forms of primary prophylaxis for PCP or toxoplasmosis assigned to the participant under the protocol. Patients who develop intolerance to all forms of prophylaxis assigned in this protocol or who develop PCP or toxoplasmosis may receive alternate or investigation forms of prophylaxis with or without zidovudine but must continue to be followed under this protocol.
• Discouraged but allowed: AL-721.
• Chronic acyclovir.
• Ketoconazole.
• Amphotericin B.
• Corticosteroids at greater than physiologic replacement doses are strongly discouraged.
• They should be used as briefly as possible and only for definite specific indications.

Patient must conform to the following:

• Receiving or candidates for zidovudine therapy at least 500 mg/day under current labeled indications with no history of pneumocystosis (PCP) or toxoplasmosis.
• Evidence of HIV infection documented by HIV antibody tests.
• T4 cell count less than 200 cells/mm3 at any time prior to study entry.
• Willing to sign informed consent.
• Willing to be followed by a participating ACTG center for duration of the study.
• Allowed: Concurrent enrollment in long-term follow-up studies in previously blinded trials of AZT (ACTG 016 and 019).

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions are excluded:

• History of documented or presumed pneumocystosis (PCP) or toxoplasmosis.
• Active bacterial or mycobacterial infection.
• History of type I hypersensitivity, exfoliative rash, or rash with mucosal involvement, severe bronchospasm, or other life-threatening reaction to any of the study drugs or to other sulfas, sulfones, or pentamidine.
• History of intolerance causing dose interruption while receiving zidovudine at equal to or less than 600 mg/day or causing dose reduction to less than 500 mg/day within 4 weeks prior to entry.
• Advanced Kaposi's sarcoma or other malignancy not specifically allowed that has been rapidly progressive during the month prior to enrollment or which may be expected to require chemotherapy within 90 days of study entry.

Concurrent Medication:

Excluded:

• Active primary treatment for an infection or malignancy.
• Other form of antifolate medication not specifically allowed.
• Other antiretroviral or biologic response modifier.
• Ganciclovir, if it causes intolerance to AZT equal to or more than 500 mg/day.
• Foscarnet.

Patients with the following are excluded:

• Symptoms and conditions defined in Exclusion Coexisting Conditions.
• Glucose 6-phosphate dehydrogenase deficiency (GPD).
• History of pneumocystosis (PCP) or toxoplasmosis.
• History of type I hypersensitivity, exfoliative rash, or rash with mucosal involvement, severe bronchospasm, or other life-threatening reaction to any of the study drugs or to other sulfas, sulfones, or pentamidine.
• History of intolerance causing dose interruption while receiving zidovudine at equal to or less than 500 mg/day with 4 weeks pior to study entry.

Prior Medication:

Excluded within 4 weeks of study entry:

• Any other form of pneumocystosis (PCP) chemoprophylaxis.
• Active substance abuse, including alcohol.

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