Risk factors for prophylaxis failure in patients receiving aerosol pentamidine for Pneumocystis carinii pneumonia prophylaxis

Objective: The purposes of this study were (1) to determine the incidence o f prophylaxis,failure in HIV-infected patients receiving aerosol pentamidin e (AP) for Pneumocystis carinii pneumonia (PCP) prophylaxis, and (2) to ide ntify risk factors for PCP prophylaxis failure. Setting and design: In Ontario, Canada, AP has been made available for outp atient PCP prophylaxis through a centralized government program, the Ontari o Drug Distribution and Monitoring Program. Data from this administrative o bservational database were extracted for 2,227 patients who received AP bet ween May 1989 and December 1998. Outcome measurements: The incidence of breakthrough PCP (BPCP) was calculat ed from the database, A Cox regression model with time-varying covariates w as created to examine factors associated with BPCP, The follow-up time was divided into three eras: 1989 to. 1991, 1992 to 1994, and 1995 to 1998, The se eras were meant to reflect major changes in antiretroviral medication re gimens, Results: The overall risk of BPCP was 16.2% over a mean follow-up of 1.67 y ears. The overall BPCP rate was 9.7/100 patient-years, with rates of 8.8/10 0, 13.1/100, and 6.3/100 patient-years in each of the three treatment eras. In the multivariate analysis, significant risk factors for prophylaxis fai lure were low CD4 count, previous diagnosis of PCP, history of AIDS-definin g conditions other than PCP, and antiretroviral treatment era defined above . Conclusion: The overall rate of PCP prophylaxis failure has decreased signi ficantly after 1995, coincident with the era of highly active antiretrovira l therapies. Initiation of PCP prophylaxis remains necessary in patients wi th risk factors.