4th Conference on Retroviruses and Opportunistic Infections Washington, DC - January 22-26, 1997

Conf Retroviruses Opportunistic Infect 1997 Jan 22-26; 4th:65 (abstract no. 3)

Locke A, Meshnick S, Lane B, Cannon M, Kileen A, Beals T, Hossler P, Kazanjian P, Bartlett M, Smith J; University of Michigan, Ann Arbor, MI.

Purpose: P. carnii pneumonia (PCP) breakthroughs on sulfa prophylaxis (TMP/SMX or dapsone) occur, but the mechanism is unknown. The purpose of this study is to determine whether mutations in the P. carinii dihydropteroate synthase (DHPS) gene are associated with these breakthroughs.

Methods: 14 patients with AIDS and PCP were identified. Use of prophylaxis within one year of episode was recorded. Broncheolaveolar lavage slides from each patient were analyzed by single or nested PCR followed by DNA sequencing.

Results: Of the 14 AIDS, 7 had received prophylaxis against PCP; TMP/SMX or dapsone was used in 6 of these 7 patients. Mutations at only 2 nucleotide positions were detected resulting in a thr55 to ala55 and/or a pro57 to ser57 change. One or both of these mutations were found in 6 of 14 patients (Table 1). 4 of the 6 patients with mutant P. carinii infections had received prophylaxis with a sulfa drug within one year prior to the episode studied, compared to 2 of 8 patients who had not received sulfa. There was a statistically significant association between sulfa prophylaxis and DHPS mutations (p is less than 0.05). (Table: see text)

Conclusion: Mutations in the P. carinii DHPS gene are associated with prophylaxis breakthroughs. Thus, drug resistance mutations may occur in P. carinii and contribute to clinical failures of sulfa drugs as PCP prophylactic agents.

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