7th Conference - Abstract 229

Pneumocystis carinii Mutations Are Associated with Duration of Sulfa Prophylaxis and with Sulfa Treatment Failure in AIDS Patients

P. KAZANJIAN*¹, W. ARMSTRONG¹, P. A. HOSSLER¹, J. RICHARDSON², L. CRANE³, J. KATZ⁴, W. BURMAN⁵, and S. R. MESHNICK¹. ¹Univ. of Michigan Hlth. System, Ann Arbor; ²Indiana Med. Ctr., Indianapolis; ³Wayne State Med. Ctr., Detroit, MI; ⁴Harvard Med. Ctr., Boston, MA; and ⁵Denver Hlth. Med. Ctr., CO

Background: We have shown that P carinii mutations are more common in AIDS patients with PCP who fail sulfa (trimethoprim/sulfamethoxazole or dapsone) prophylaxis. This study was performed to determine if dose and duration of sulfa prophylaxis influence mutations and whether mutations effect response to sulfa therapy.
Methods: Portions of the gene for the P carinii dihydropteroate synthase from 97 AIDS patients with PCP from four geographic regions (Boston, Indianapolis, Denver, and Detroit) were PCR-amplified and sequenced. Charts were reviewed, without knowledge of the genotypic data, to quantify exposure to sulfa prophylaxis and assess response to sulfa treatment.
Results: Mutations were observed in 28 of 37 (76%) isolates from AIDS patients receiving sulfa prophylaxis compared with only 14 of 60 (23%) who did not (p=0.001). Duration of sulfa prophylaxis significantly increased the risk of mutations (RR for each month of sulfa exposure=1.06; p=0.02). Mutations significantly increased the risk of sulfa treatment failure (RR 2.1; p=0.01), but not the risk of failure to therapy with non-sulfa agents (RR 1.003; p=0.1). There was no significant association between choice of sulfa agent, dose of agent, or geographic location with P carinii mutations.
Conclusions: This study confirms that mutations are significantly more common in AIDS patients with PCP who fail sulfa prophylaxis. This is the first study to demonstrate that an increased duration of sulfa prophylaxis increases the chance of developing a mutation and that mutations reduce the response to sulfa treatment but have no effect on response to treatment with non-sulfa agents.

Key Words: Mutations, Pneumocystis, Sulfa