TRIMETHOPRIM-SULFAMETHOXAZOLE VERSUS AEROSOLIZED PENTAMIDINE FOR PRIMARY PROPHYLAXIS OF PNEUMOCYSTIS-CARINII PNEUMONIA - A PROSPECTIVE, RANDOMIZED, CONTROLLED CLINICAL-TRIAL

The objective was to compare the efficacy and tolerance of monthly aer osolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, pros pective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts <200/mm(3) or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TM P-SMX (400-80 mg). The mean followup was 578 days. The two groups (exc ept for gender) were homogeneous for age, risk group for HIV infection , initial CD4(+) lymphocyte count, and mean follow-up. The PCP rate pe r year of observation using an intent-to-treat analysis was 3.1% and 1 .3% in the groups treated with pentamidine and TMPSMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05) . Nineteen episodes of cerebral toxoplasmosis were diagnosed during th e study. The analysis showed no significant difference in time of deve lopment of toxoplasmosis, but only one patient was actually treated wi th TMP-SMX. Survival was not significantly different in the two groups . Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectivel y prevented a first episode of PCP in HIV-infected patients, but aeros olized pentamidine was better tolerated. However, TMPSMX is less costl y and should have a preventive effect for toxoplasmosis.