Risk Factors for Prophylaxis Failure in Patients Receiving Aerosol Pentamidine for Pneumocystis carinii Pneumonia Prophylaxis

Abstract

The purposes of this study were (1) to determine the incidence of prophylaxis failure in HIV-infected patients receiving aerosol pentamidine (AP) for Pneumocystis carinii pneumonia (PCP) prophylaxis, and (2) to identify risk factors for PCP prophylaxis failure. In Ontario, Canada, AP has been made available for outpatient PCP prophylaxis through a centralized government program, the Ontario Drug Distribution and Monitoring Program. Data from this administrative observational database were extracted for 2,227 patients who received AP between May 1989 and December 1998. The incidence of breakthrough PCP (BPCP) was calculated from the database. A Cox regression model with time-varying covariates was 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. These eras were meant to reflect major changes in antiretroviral medication regimens. The overall risk of BPCP was 16.2% over a mean follow-up of 1.67 years. The overall BPCP rate was 9.7/100 patient-years, with rates of 8.8/100, 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 failure were low CD4 count, previous diagnosis of PCP, history of AIDS-defining conditions other than PCP, and antiretroviral treatment era defined above. The overall rate of PCP prophylaxis failure has decreased significantly after 1995, coincident with the era of highly active antiretroviral therapies. Initiation of PCP prophylaxis remains necessary in patients with risk factors.