Trimethoprim-sulfamethoxazole (TMP-SMZ) dose escalation versus direct rechallenge for Pneumocystis carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with previous adverse reaction to TMP-SMZ

Trimethoprim-sulfamethoxazole (TMP-SMZ) is the most effective Pneumocystis carinii pneumonia (PCP) prophylactic agent, but adverse reactions are commo n among human immunodeficiency virus (HIV)-infected patients and limit its use. This randomized, double-blind controlled trial compared 2 methods of T MP-SMZ reintroduction, 6-day dose escalation and direct rechallenge, for PC P prophylaxis in HIV-infected patients who had experienced previous treatme nt-limiting reactions. The primary end point was the ability to take single -strength TMP-SMZ daily for 6 months. Seventy-five percent of the dose-esca lation group and 57% of the direct-rechallenge group continued to receive d aily single-strength TMP-SMZ for 6 months. Among premature discontinuations , 58% of the dose-escalation group and 70% (P = .014). of the direct-rechal lenge group were due to adverse reactions. None of these reactions was seri ous. This study provides evidence that it is possible to successfully reint roduce TMP-SMZ to a significant proportion of HIV-infected patients who hav e experienced mild-to-moderate treatment-limiting adverse reactions.