Risk Factors for Breakthrough Pneumocystis carinii Pneumonia on Aerosol Pentamidine Prophylaxis

OBJECTIVE: To identify baseline characteristics of human immunodeficiency virus (HIV)-infected individuals on aerosol pentamidine for Pneumocystis carinii prophylaxis that are predictive of subsequent breakthrough Pneumocystis carinii pneumonia (PCP).DESIGN: Nested case-control study assembled from a cohort of patients enrolled in the Toronto aerosol pentamidine program.METHODS: Subjects were selected from a cohort of HIV-infected individuals were enrolled in a community based aerosol pentamidine program between May 1989 and May 1992 in Toronto, Ontario. Cases - individuals who had breakthrough PCP - were matched with up to two controls enrolled in the same week. Risk factors examined for development of PCP for both primary and secondary prophylaxis included age, sex, smoking history, evidence of bronchospasm during aerosol pentamidine administration (fall of forced expiratory volume [FEV] 15% or more), administration of salbutamol before aerosol pentamidine, pulmonary function tests including lung volumes, flow rates and diffusing capacity for carbon monoxide. In the primary prophylaxis group, CD4 count at enrolment and in the secondary prophylaxis group, time from the most recent episode of PCP to enrolment for aerosol pentamidine and total time from the most recent episode of PCP to breakthrough PCP were examined as additional risk factors.RESULTS: A total or 1344 patients we re enrolled in the aerosol pentamidine program, 78% for primary prophylaxis and 22% for secondary prophylaxis. At the time of census at the end or 1992 there had been 96 episodes or breakthrough PCP, 5% on primary prophylaxis and 14.5% on secondary prophylaxis. In the primary prophylaxis group, enrolment CD4 count was significantly lower in the cases developing breakthrough PCP: 116±74 compared with 175±85 cells/mm3 in the control group (P=0.001). There was no difference in any other variable. In the secondary prophylaxis group, time from the most recent episode of PCP to initiation of aerosol pentamidine therapy was longer in the cases developing breakthrough PCP: mean delay 6.1±6.6 months compared with 3.1±2.1 in controls (P=0.02). There was no difference in the other variables examined.CONCLUSIONS: The results of this study support immune augmentation for patients receiving aerosol pentamidine for primary prophylaxis, and aerosol pentamidine should be recommenced as soon as possible following an episode of PCP, for secondary prophylaxis.