Pneumocystis carinii cytochrome b mutations are associated with atovaquone exposure in patients with AIDS.
This retrospective cohort study was conducted to determine whether Pneumocystis carinii cytochrome b gene mutations in patients with AIDS and P. carinii pneumonia (PCP) are associated with atovaquone exposure. Portions of the P. carinii cytochrome b genes that were obtained from 60 patients with AIDS and PCP from 6 medical centers between 1995 and 1999 were amplified and sequenced by using polymerase chain reaction. Fifteen patients with previous atovaquone prophylaxis or treatment exposure were matched with 45 patients with no atovaquone exposure. Cytochrome b coenzyme Q binding site mutations were observed in 33% of isolates from patients exposed to atovaquone, compared with 6% from those who were not (P=.018). There was no difference in survival 1 month after treatment between patients with or without cytochrome b mutations (P=.14). Thus, cytochrome b mutations are significantly more common in patients with AIDS and PCP with atovaquone exposure, but the clinical significance of these mutations remains unknown.
Kazanjian
P
P
Department of Internal Medicine, University of Michigan Health System, 1500 E. Medical Center Dr., Rm. 3120B TC, Ann Arbor, MI 48109-0378, USA. pkazanji@umich.edu
Armstrong
W
W
Hossler
P A
PA
Lee
C H
CH
Huang
L
L
Beard
C B
CB
Carter
J
J
Crane
L
L
Duchin
J
J
Burman
W
W
Richardson
J
J
Meshnick
S R
SR
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D053626:Atovaquone; D016022:Case-Control Studies; D015331:Cohort Studies; D003573:Cytochrome b Group / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009285:Naphthoquinones / Q000009:adverse effects* / Q000627:therapeutic use; D011010:Pneumocystis / Q000187:drug effects* / Q000235:genetics; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D013534:Survival; D016896:Treatment Outcome; D014451:Ubiquinone / Q000187:drug effects / Q000235:genetics
D000935:Antifungal Agents; D003573:Cytochrome b Group; D009285:Naphthoquinones; D014451:Ubiquinone; D053626:Atovaquone