Efficacy and toxicity of two doses of trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus. Dutch AIDS Treatment Group.

The efficacy and toxicity of trimethoprim-sulfamethoxazole (TMP-SMZ) as primary prophylaxis against Pneumocystis carinii pneumonia (PCP) for patients with human immunodeficiency virus (HIV) infection was assessed by comparing the effects of two dosages (480 or 960 mg once a day) of the drug. The multicenter trial involved 260 HIV-infected patients with CD4 cell counts < 0.2 x 10(9)/L and no history of PCP. Patients were randomly assigned to the treatment groups. After a median follow-up of 376 days (range, 1-1219), none of the patients developed PCP. Most adverse reactions that required discontinuation were seen within the first month of TMP-SMZ use and were seen more frequently and earlier in the 960-mg group (hazard ratio, 1.4; 95% confidence interval, 0.95-2.02; P = .007). For patients with HIV infection, 480 mg of TMP-SMZ is as efficacious as but less toxic than 960 mg of the drug for primary prophylaxis against PCP.

A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. The Dutch AIDS Treatment Group.

BACKGROUND: Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) is recommended for patients with human immunodeficiency virus (HIV) infection if their CD4 cell counts are below 200 per cubic millimeter (0.2 x 10(9) per liter). Either aerosolized pentamidine or trimethoprim-sulfamethoxazole (co-trimoxazole) is commonly prescribed for prophylaxis, but the relative efficacy and toxicity of these agents are unknown. METHODS: We conducted a multicenter trial involving 215 HIV-infected patients with no history of PCP but with CD4 cell counts below 200 per cubic millimeter. The patients were randomly assigned to one of three regimens: aerosolized pentamidine once a month, 480 mg of trimethoprim-sulfamethoxazole once a day (80 mg of trimethoprim and 400 mg of sulfamethoxazole), or 960 mg of trimethoprim-sulfamethoxazole once a day (160 mg and 800 mg, respectively). The cumulative incidence of PCP was estimated by Kaplan-Meier survival analysis. RESULTS: After a mean follow-up of 264 days, 6 of the 71 patients in the pentamidine group had a confirmed first episode of PCP (11 percent), whereas none of the 142 patients in the two trimethoprim-sulfamethoxazole groups had PCP (P = 0.002). However, adverse events that required discontinuation of the medication were much more frequent in the trimethoprim-sulfamethoxazole groups (17 and 18 patients) than in the pentamidine group (2 patients). The adverse reactions occurred significantly sooner in the group given 960 mg of trimethoprim-sulfamethoxazole than in the group given 480 mg (mean time, 16 vs. 57 days; P = 0.02). CONCLUSIONS: For patients with HIV infection, trimethoprim-sulfamethoxazole taken once a day is more effective as primary prophylaxis against PCP than aerosolized pentamidine administered once a month, although adverse drug reactions are more frequent with trimethoprim-sulfamethoxazole.