Severity and outcome of HIV-associated Pneumocystis pneumonia containing Pneumocystis jirovecii dihydropteroate synthase gene mutations

Background: The impact of Pneumocystis jirovecii (formerly P. carinii) dihydropteroate synthase (DHPS) gene mutations on morbidity and mortality of Pneumocystis pneumonia (PCP) in HIV-positive patients is unclear. Objective: To determine whether severity and outcome of HIV-associated PCP differes according to DHPS genotype. Setting: A prospective, observational study in a university-affiliated county hospital. Patients: The study included 197 patients with 215 microscopically confirmed PCP episodes and successfully sequenced DHPS genotypes; 175 (81 %) episodes displayed mutant genotypes. Main outcome measure: All-cause mortality within 60 days. Results: The majority of patients (86 %) with PCP containing Pneumocystis DHPS mutations survived. Although severity of PCP was comparable, there was a trend for more patients with mutant genotypes than patients with wild-type to require mechanical ventilation (14.3 % versus 2.5 %; P = 0.056) and to die (14.3 % versus 7.5 %, P = 0.31). Independent predictors of mortality at baseline were low serum albumin levels [odds ratio (OR), 4.62; 95 % confidence interval (Cl), 1.63-13.1; P = 0.004] and requiring intensive care within 72 h of hospitalization (OR, 5.06; 95 % Cl, 1.43-18.0; P = 0.012). Conclusion: The majority of HIV-infected patients with PCP containing mutant Pneumocystis DHPS genotypes survived. Mortality was related primarily to the underlying severity of illness. However, a trend towards increased mortality in episodes of PCP containing mutant DHPS genotypes was observed and this warrants further study. (c) 2005 Lippincott Williams & Wilkins.