Inclusion Criteria

Patients must fulfill the following criteria:

• Randomization within 10 weeks of completing therapy for Pneumocystis carinii pneumonia (PCP).
• Ability to tolerate oral and aerosolized therapy at the time of randomization.
• Life expectancy > 4 months.

Concurrent Medication:

Allowed:

• Inhaled bronchodilators for cough and bronchospasm related to aerosolized pentamidine treatment.
• Aspirin at modest doses.
• Ibuprofen at modest doses.
• Acetaminophen at modest doses.
• Erythropoietin for management of anemia.
• Allowed to treat opportunistic infections while on study:
• Acyclovir.
• Ketoconazole.
• Amphotericin B.
• Nystatin.
• Clotrimazole.
• Also allowed:
• Ganciclovir (DHPG) for maintenance therapy of life-threatening or sight-threatening cytomegalovirus retinitis (CMV retinitis) infection only.
• Zidovudine (AZT) must be discontinued during the acute induction phase of treatment and will be restarted when maintenance therapy is introduced.

Concurrent Treatment:

Allowed:

• Local radiation therapy for Kaposi's sarcoma.

Prior Medication:

Allowed:

• Primary prophylactic therapy prior to Pneumocystis carinii pneumonia (PCP) episode.

Risk Behavior:

Allowed:

• Patients maintained in a methadone maintenance program per local investigator's judgment.

Exclusion Criteria

• Active drug or alcohol abuse which would impair performance as a study subject.

Concurrent Medication:

Excluded:

• Famotidine.
• Any medications suspected of interference with the metabolism of zidovudine.
• Flurazepam.
• Chronic probenecid.
• Phenobarbital.
• Phenytoin.
• Experimental therapies, except as noted.
• Chronic oral bronchodilators should not be started in patients in order to maintain them on aerosolized pentamidine after they have exhibited pulmonary toxicity.

Prior Medication:

Excluded for the 30 patients who will undergo pharmacokinetic studies:

• Zidovudine (AZT) at any time.
• Excluded within 7 days of study entry for the 30 patients who will undergo pharmacokinetic studies:
• Trimethoprim / sulfamethoxazole.
• Pyrimethamine / sulfadoxine.
• Aerosolized pentamidine.
• Excluded:
• Pentamidine by any route for the original infection.
• Prophylactic therapy for Pneumocystis carinii pneumonia (PCP) between the discontinuation of acute treatment and study entry.

Prior Treatment:

Excluded within 2 weeks of study entry:

• Transfusions of blood or red blood cells.

Patients may not have any of the following symptoms or diseases:

• Known treatment-limiting hypersensitivity to sulfonamides, trimethoprim, pyrimethamine, pentamidine, or zidovudine (AZT), especially but not limited to, exfoliative dermatitis, erythema multiforme, and Stevens-Johnson syndrome.
• Development of severe hypoglycemia (serum glucose < 50 mg/dl with pentamidine therapy).
• History of neoplasms other than basal cell carcinoma of the skin or carcinoma in situ of the cervix, or mucocutaneous Kaposi's sarcoma.
• Known visceral Kaposi's sarcoma.
• Known glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.