Pneumocystis carinii mutations are associated with duration of sulfa or sulfone prophylaxis exposure in AIDS patients

This study was conducted to determine whether Pneumocystis carinii dyhydrop teroate synthase (DHPS) gene mutations in AIDS patients with P. carinii pne umonia (PCP) are affected by duration of sulfa or sulfone prophylaxis and i nfluence response to sulfa or sulfone therapy. The P. carinii DHPS genes fr om 97 AIDS patients with PCP between 1991 and 1999 from 4 medical centers w ere amplified, using polymerase chain reaction (PCR), and sequenced, Mutati ons were observed in 76% of isolates from patients exposed to sulfa or sulf one prophylaxis compared with 23% of isolates from patients not exposed (P = .001). Duration of prophylaxis increased the risk of mutations (relative risk [RR] for each exposure month, 1.06; P = .02), Twenty-eight percent of patients with mutations failed sulfa or sulfone treatment; mutations increa sed the risk of sulfa or sulfone treatment failure (RR, 2.1; P = 0.01), Thu s, an increased duration of sulfa or sulfone prophylaxis increases the chan ce of developing a P. carinii mutation. The majority of patients with mutat ions respond to sulfa or sulfone therapy.