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

JAMA. 1995 Apr 19;273(15):1197-202.

Abstract

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.

Publication types

  • Multicenter Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy
  • AIDS-Related Opportunistic Infections / immunology
  • AIDS-Related Opportunistic Infections / mortality
  • AIDS-Related Opportunistic Infections / prevention & control*
  • Adult
  • CD4 Lymphocyte Count
  • Dapsone / therapeutic use
  • HIV Infections / immunology*
  • HIV Infections / mortality
  • HIV Infections / therapy*
  • HIV-1*
  • Humans
  • Immune Tolerance
  • Longitudinal Studies
  • Male
  • Multivariate Analysis
  • Pentamidine / therapeutic use
  • Pneumonia, Pneumocystis / drug therapy
  • Pneumonia, Pneumocystis / immunology
  • Pneumonia, Pneumocystis / mortality
  • Pneumonia, Pneumocystis / prevention & control*
  • Proportional Hazards Models
  • Recurrence
  • Survival Analysis
  • Treatment Failure
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use

Substances

  • Pentamidine
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Dapsone