Inclusion Criteria

Concurrent Medication:

Allowed:

• Noninvestigational therapies as needed.
• Maintenance therapy with investigational triazoles such as itraconazole and SCH 39304.
• High-dose corticosteroids (exceed physiologic replacement doses) including oral prednisone 40 mg bid for 5 days, 40 mg daily for 5 days and then 20 mg daily for the remainder of PCP therapy. Same dose for methylprednisolone.

Concurrent Treatment:

Allowed:

• Any ventilatory support, antihypertensive agents, invasive monitoring, and other necessary medical intervention, according to his/her medical status, personal wishes, and the judgment of his/her physician.

Patients must have:

• HIV seropositivity.
• Diagnosis of Pneumocystis carinii pneumonia (PCP).
• Serious intolerance to trimethoprim / sulfamethoxazole (TMP / SMX) therapy defined as follows:
• Platelets < 50000 platelets/mm3.
• Neutrophil count (polys plus bands) = or < 500 cells/mm3 on at least two occasions = or > 12 hours apart.
• Mucocutaneous reaction - blistering rash, mucosal involvement, generalized maculopapular eruption, or intolerable pruritus.
• Hepatitis demonstrated by transaminase elevation > 5 times the upper limit of normal, or = or > 300 IU if baseline is abnormal.
• Drug fever with daily temperature = or > 103 degrees F beginning after the 5th day of treatment persisting for at least 3 days and not responsive to antipyretic therapy, with no other discernible cause.
• Any other severe or life-threatening adverse reaction to TMP / SMX which, in the investigator's opinion, makes continued or recurrent treatment with TMP / SMX inadvisable as determined on a case-by-case basis.
• Serious intolerance to pentamidine therapy defined as follows:
• Platelets < 50000 platelets/mm3.
• Neutrophil count (polys plus bands) = or < 500 cells/mm3 on at least two occasions = or > 12 hours apart.
• Serum creatinine > 3.0 mg/dl.
• Systolic blood pressure < 90 mm requiring supportive therapy.
• Symptomatic hypoglycemia with blood glucose < 40, or hyperglycemia requiring therapy.
• Pancreatitis with laboratory confirmation (abnormal amylase and/or lipase).
• Any other severe or life-threatening adverse reaction to pentamidine, which, in the investigator's opinion, makes continued or recurrent treatment with pentamidine inadvisable as determined on a case-by-case basis.
• Informed consent by patient or legal guardian.

Prior Medication:

Required:

• Trimethoprim / sulfamethoxazole and pentamidine therapies.

Prior Medication:

Allowed:

• Myelosuppressive or nephrotoxic agents including zidovudine.

History of high-risk behavior for HIV infection - homosexual or bisexual men, intravenous drug abusers, recipients of HIV-infected blood products, or sexual partners of persons in these groups may be admitted without proof of HIV infection.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reactions due to trimetrexate.
• Patients with a less severe adverse reaction may be enrolled if, in the opinion of the investigator, these adverse effects do not prohibit rechallenge with the drug.

Concurrent Medication:

Excluded:

• Myelosuppressive or nephrotoxic agents including zidovudine and ganciclovir.
• Investigational therapies.

Patients with the following are excluded:

• History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reactions due to trimetrexate.
• Patients with a less severe adverse reaction may be enrolled if, in the opinion of the investigator, these adverse effects do not prohibit rechallenge with the drug.