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 differs according to DHPS genotype.


METHODS
A prospective, observational study in a university-affiliated county hospital.


METHODS
The study included 197 patients with 215 microscopically confirmed PCP episodes and successfully sequenced DHPS genotypes; 175 (81%) episodes displayed mutant genotypes.


METHODS
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 (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).


CONCLUSIONS
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.
Crothers
Kristina
K
Positive Health Program and Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA. kristina.crothers@yale.edu
Beard
Charles B
CB
Turner
Joan
J
Groner
Gena
G
Fox
Melissa
M
Morris
Alison
A
Eiser
Shary
S
Huang
Laurence
L
D017088:AIDS-Related Opportunistic Infections / Q000401:mortality / Q000821:virology*; D000328:Adult; D004094:Dihydropteroate Synthase / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000401:mortality / Q000821:virology; D015497:HIV-1; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D045363:Pneumocystis carinii / Q000201:enzymology*; D011020:Pneumonia, Pneumocystis / Q000401:mortality* / Q000821:virology*; D011446:Prospective Studies
D004094:Dihydropteroate Synthase