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

Abstract

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. To determine whether severity and outcome of HIV-associated PCP differs according to DHPS genotype. A prospective, observational study in a university-affiliated county hospital. The study included 197 patients with 215 microscopically confirmed PCP episodes and successfully sequenced DHPS genotypes; 175 (81%) episodes displayed mutant genotypes. All-cause mortality within 60 days. 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 (CI), 1.63-13.1; P = 0.004] and requiring intensive care within 72 h of hospitalization (OR, 5.06; 95% CI, 1.43-18.0; P = 0.012). 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.