To evaluate the safety of the combination of trimetrexate glucuronate (TMTX) and dapsone
with leucovorin protection versus trimethoprim/sulfamethoxazole (TMP/SMX) in patients with
AIDS and moderately severe Pneumocystis carinii pneumonia (PCP). To determine the
pharmacokinetic parameters of TMTX, leucovorin, and dapsone and of TMP/SMX when given to
patients with AIDS and moderately severe PCP.
- Empiric therapy for other opportunistic pulmonary infection (TB or fungi) for the
first 72 hours of study enrollment ONLY, until presence of suspected pathogens can be
Patients must have:
- Confirmed diagnosis of PCP.
- Alveolar-arterial differences in dissolved oxygen >= 35 mm Hg but < 55 mm Hg on room
Patients with the following symptoms or conditions are excluded:
- Severe renal or hepatic dysfunction.
- Serious or life-threatening intolerance to TMP/SMX, TMTX, or dapsone.
- Concurrent pneumothorax.
- Active pulmonary tuberculosis or other inadequately treated opportunistic pulmonary
infection (e.g., Cryptococcus neoforms, CMV). NOTE:
- Identification of Mycobacterium avium or CMV in sputum or BAL fluid does not exclude,
since these organisms may be present without causing disease.
- Pulmonary Kaposi's sarcoma.
- Active opportunistic infections or malignancies requiring induction therapy with bone
marrow suppressive drugs (e.g., ganciclovir) or hepatotoxic drugs (e.g.,
- Unable to have arterial blood gases on room air obtained at baseline.
- Unwilling to undergo bronchoscopy, if sputum induction does not reveal Pneumocystis
- Suspected malabsorption (e.g., ileus or severe diarrhea with > 6 stools/day).
- Known absence of G6PD activity.
- Large volume (1.0 to 1.5 liters) of intravenous fluid (5 percent in water) per 24
hours is medically inadvisable.
- Unwilling to comply with study design.
- Induction therapy with bone marrow suppressive drugs (e.g., ganciclovir) or
hepatotoxic drugs (e.g., chemotherapy).
- AZT, ddI, ddC, d4T, or other antiretroviral therapy.
Patients with the following prior condition are excluded:
Prior history of serious or life-threatening intolerance to TMP/SMX. (NOTE:
- Patients with less severe reactions may be included at the discretion of the
investigator and primary care provider.)
- More than 24 hours of systemic anti-PCP therapy within 2 weeks prior to study entry.