Predictors for failure of Pneumocystis carinii pneumonia prophylaxis. Multicenter AIDS Cohort Study.

Objective: To identify clinical and epidemiological factors associated with failure of Pneumocystis carinii pneumonia (PCP) prophylaxis in those receiving primary and secondary prophylaxis.

Design: Longitudinal cohort study of participants infected with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study who used PCP prophylaxis regimens after their T-helper lymphocyte counts had decreased to less than 0.200 x 10(9)/L (200/microL).

Main Outcome Measure: Occurrence or recurrence of PCP.

Results: A total of 476 participants reported taking one or more of the following regimens: trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, and/or aerosolized pentamidine--367 as primary prophylaxis and 109 as secondary prophylaxis after a previous episode of PCP. A total of 92 (20%) developed PCP despite prophylaxis. The mean failure rates per person-year of follow-up were 16.0% for those receiving primary prophylaxis and 12.1% for those receiving secondary prophylaxis (P = .19). Median times to death after initiation of primary or secondary prophylaxis were 2.0 and 1.2 years, respectively. The main predictor for failure of PCP prophylaxis was profound T-helper lymphocytopenia; 86% of failures occurred after T-helper cell counts decreased to less than 0.075 x 10(9)/L and 76% occurred after counts decreased to less than 0.050 x 10(9)/L. In multivariate time-dependent analysis, when compared with counts between 0.100 x 10(9)/L and 0.200 x 10(9)/L, the risk ratio for failure with counts less than 0.050 x 10(9)/L was 2.90 (P < .001). Once T-helper cell counts were considered, fever was the only other health status indicator that predicted subsequent PCP (ie, a time-dependent risk ratio of 2.22; P = .01). Use of TMP-SMX as the prophylaxis regimen was protective but did not eliminate failure (ie, a time-dependent risk ratio of 0.55; P = .03).

Conclusions: These findings strongly support identifying improved methods of PCP prophylaxis once T-helper cell counts decrease to less than 0.075 x 10(9)/L or 0.100 x 10(9)/L. Given this severe degree of immunosuppression, an inherently more effective regimen against P carinii is required.