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 dyhydropteroate synthase (DHPS) gene mutations in AIDS patients with P. carinii pneumonia (PCP) are affected by duration of sulfa or sulfone prophylaxis and influence response to sulfa or sulfone therapy. The P. carinii DHPS genes from 97 AIDS patients with PCP between 1991 and 1999 from 4 medical centers were amplified, using polymerase chain reaction (PCR), and sequenced. Mutations were observed in 76% of isolates from patients exposed to sulfa or sulfone 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 increased the risk of sulfa or sulfone treatment failure (RR, 2.1; P=0.01). Thus, an increased duration of sulfa or sulfone prophylaxis increases the chance of developing a P. carinii mutation. The majority of patients with mutations respond to sulfa or sulfone therapy.
Division of Infectious Diseases, Dept. of Medicine, University of Michigan Health System, Ann Arbor, MI 48109-0378, USA. pkazanji@umich.edu
P
P
Kazanjian
W
W
Armstrong
P A
PA
Hossler
W
W
Burman
J
J
Richardson
C H
CH
Lee
L
L
Crane
J
J
Katz
S R
SR
Meshnick
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D003622:Dapsone / Q000627:therapeutic use*; D004094:Dihydropteroate Synthase / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011010:Pneumocystis / Q000235:genetics*; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000188:drug therapy*; D013450:Sulfones / Q000627:therapeutic use; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D014481:United States
D013450:Sulfones; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D003622:Dapsone; D004094:Dihydropteroate Synthase