Effect of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of P carinii pneumonia in patients with HIV-1: a prospective study.
BACKGROUND
Investigators have reported that patients infected with Pneumocystis carinii containing mutations in the DHPS (dihydropteroate synthase) gene have a worse outcome than those infected with P carinii containing wild-type DHPS. We investigated patients with HIV-1 infection and P carinii pneumonia to determine if DHPS mutations were associated with poor outcomes in these patients.


METHODS
We compared presence of mutations at the DHPS locus with survival and response of patients to co-trimoxazole or other drugs.


RESULTS
For patients initially given co-trimoxazole, nine (14%) of 66 with DHPS mutant died, compared with nine (25%) of 36 with wild type (risk ratio50.55 [95% CI=0.24-1.25]; p=0.15). Ten (15%) of 66 patients with a DHPS mutant did not respond to treatment, compared with 13 (36%) of 36 patients with the wild type (0.42 [0.20-0.86]; p=0.02). For patients aged 40 years or older, four (14%) of 29 with the mutant and nine (56%) of 16 with the wild type died (0.25 [0.09-0.67]; p=0.005).


CONCLUSIONS
These results, by contrast with those of previous studies, suggest that patients with wild-type P carinii do not have a better outcome than patients with the mutant when given co-trimoxazole. Our results suggest that presence of a DHPS mutation should be only one of several criteria guiding the choice of initial drug treatment of P carinii pneumonia in patients with HIV-1 infection.
Navin
T R
TR
Division of Parasitic Diseases, National Center for Infectious, Diseases, Centers for Disease Control and Prevention, United States Public Health Service, Department of Health and Human Services, Atlanta, GA, USA.
Beard
C B
CB
Huang
L
L
del Rio
C
C
Lee
S
S
Pieniazek
N J
NJ
Carter
J L
JL
Le
T
T
Hightower
A
A
Rimland
D
D
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use; D003622:Dapsone / Q000627:therapeutic use; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004352:Drug Resistance, Microbial; D005838:Genotype; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011010:Pneumocystis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D014295:Trimethoprim / Q000627:therapeutic use; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D003622:Dapsone; D014295:Trimethoprim; D004094:Dihydropteroate Synthase