Objective: 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.
design: 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.
Outcome measurements: 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.
Results: 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.
Conclusion: 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.