TRIMETREXATE WITH LEUCOVORIN VERSUS TRIMETHOPRIM-SULFAMETHOXAZOLE FORMODERATE TO SEVERE EPISODES OF PNEUMOCYSTIS-CARINII PNEUMONIA IN PATIENTS WITH AIDS - A PROSPECTIVE, CONTROLLED MULTICENTER INVESTIGATION OF THE AIDS-CLINICAL-TRIALS-GROUP PROTOCOL-029 031/

Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a double-blind study of trimetr exate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) f or 21 days. By study day 10, study therapy failed because of lack of e fficacy in 16% of patients assigned to TMP-SMZ and 27% assigned to tri metrexate (P =.064), and the PAO(2) - Pao(2) improved significantly fa ster with TMP-SMZ. By study day 21, failure rates were 20% with TMP-SM Z and 38% with trimetrexate (P =.008), with respective mortality rates of 12% and 20% (P =.088). By study day 49, the difference in mortalit y (16% vs. 31%) was significant (P = .028). The cumulative incidence o f serious and treatment-terminating adverse events including hematolog ic toxicities was less with trimetrexate (P <.001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, for modera tely severe P. carinii pneumonia but was better tolerated than TMP-SMZ .