Clinical efficacy of first- and second-line treatments for HIV-associated Pneumocystis jirovecii pneumonia: a tri-centre cohort study.
OBJECTIVE
First-line therapy for Pneumocystis jirovecii pneumonia (PCP) is trimethoprim/sulfamethoxazole. Few data exist to guide the choice of second-line therapy for patients failing or developing toxicity to first-line therapy.


METHODS
A case note review of 1122 patients with 1188 episodes of HIV-associated PCP from three observational cohorts in Copenhagen, London and Milan, between 1989 and 2004, was conducted.


RESULTS
Trimethoprim/sulfamethoxazole (962 PCP episodes, 81%) was the most frequently used first-line therapy, followed by intravenous pentamidine (87 episodes, 7%), clindamycin/primaquine (72 episodes, 6%) and 'other' (atovaquone, dapsone/pyrimethamine, trimetrexate or inhaled pentamidine; 67 episodes, 6%). Rates of unchanged therapy were trimethoprim/sulfamethoxazole = 79%, clindamycin/primaquine = 65% and pentamidine = 60% (P < 0.001). First-line therapy was changed because of failure in 82 (7%) episodes and because of toxicity in 198 (17%) episodes. Three month survival rates were trimethoprim/sulfamethoxazole = 85%, clindamycin/primaquine = 81% and pentamidine = 76% (P = 0.09). After adjustment for possible confounders, pentamidine was associated with a significantly greater risk of death at 3 months [hazard ratio (HR) = 2.0, 95% confidence interval (CI) = 1.2-3.4]. Second-line therapy survival rates differed: trimethoprim/sulfamethoxazole = 85%; clindamycin/primaquine = 87%; and pentamidine = 60% (P = 0.01). Multivariable time-updated Cox regression analysis showed a greater risk of death associated with pentamidine (HR = 3.3, 95% CI = 2.2-5.0), but not for clindamycin/primaquine, when both were compared with trimethoprim/sulfamethoxazole.


CONCLUSIONS
Pentamidine was associated with a greater risk of death when used as first- and second-line therapy for HIV-associated PCP, and was associated with more treatment changes. Clindamycin/primaquine appeared superior to pentamidine as second-line therapy for PCP in patients failing or developing toxicity with trimethoprim/sulfamethoxazole. In patients failing first-line treatment with non-trimethoprim/sulfamethoxazole regimens, second-line therapy should be trimethoprim/sulfamethoxazole.
Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark. jhelweg@dadlnet.dk
Jannik
J
Helweg-Larsen
Thomas
T
Benfield
Chiara
C
Atzori
Robert F
RF
Miller
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D002981:Clindamycin / Q000627:therapeutic use; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D006801:Humans; D007558:Italy; D008131:London; D008297:Male; D008875:Middle Aged; D010419:Pentamidine / Q000627:therapeutic use; D045363:Pneumocystis carinii / Q000302:isolation & purification*; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy*; D011319:Primaquine / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D055815:Young Adult
D000935:Antifungal Agents; D002981:Clindamycin; D010419:Pentamidine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D011319:Primaquine