PREDICTORS FOR FAILURE OF PNEUMOCYSTIS-CARINII PNEUMONIA PROPHYLAXIS

Objective.-To identify clinical and epidemiological factors associated with failure of Pneumocystis carinii pneumonia (PCP) prophylaxis in t hose receiving primary and secondary prophylaxis. Design.-Longitudinal cohort study of participants infected with human immunodeficiency vir us type 1 in the Multicenter AIDS Cohort Study who used PCP prophylaxi s regimens after their T-helper lymphocyte counts had decreased to les s than 0.200x10(9)/L (200/mu L). Main Outcome Measure.-Occurrence or r ecurrence 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 prop hylaxis and 109 as secondary prophylaxis after a previous episode of P CP. A total of 92 (20%) developed PCP despite prophylaxis. The mean fa ilure rates per person-year of follow-up were 16.0% for those receivin g primary prophylaxis and 12.1% for those receiving secondary prophyla xis (P=.19). Median times to death after initiation of primary or seco ndary prophylaxis were 2.0 and 1.2 years, respectively. The main predi ctor for failure of PCP prophylaxis was profound T-helper lymphocytope nia; 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 l ess than 0.050x10(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 onl y other health status indicator that predicted subsequent PCP (ie, a t ime-dependent risk ratio of 2.22; P=.01). Use of TMP-SMX as the prophy laxis regimen was protective but did not eliminate failure tie, a time -dependent risk ratio of 0.55; P=.03). Conclusions.-These findings str ongly support identifying improved methods of PCP prophylaxis once T-h elper 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 mor e effective regimen against P carinii is required.