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Previous Volume 328:1514-1520 May 27, 1993 Number 21 Next

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ABSTRACT

Background Pneumocystis carinii pneumonia and toxoplasmic encephalitis are frequent life-threatening opportunistic infections in patients with human immunodeficiency virus (HIV) infection. Primary prophylaxis against P. carinii pneumonia is now common, but there are few data on regimens for primary prophylaxis against toxoplasmosis.

Methods We conducted a randomized trial that compared two prophylactic regimens: dapsone (50 mg per day) plus pyrimethamine (50 mg per week) was compared with aerosolized pentamidine (300 mg per month). The patients had symptomatic HIV infection, no history of P. carinii pneumonia or symptomatic toxoplasmosis, and CD4+ counts below 200 per cubic millimeter (0.2 x 10⁹ per liter).

Results In an intention-to-treat analysis, after a median follow-up of 539 days P. carinii pneumonia developed in 10 patients in each group, whereas toxoplasmosis developed in 32 of 176 patients in the pentamidine group and 19 of 173 patients in the dapsone-pyrimethamine group. Those assigned to pentamidine had a risk of P. carinii pneumonia that was similar to the risk in those assigned to dapsone-pyrimethamine (adjusted relative risk, 1.13; 95 percent confidence interval, 0.44 to 2.92; P = 0.79), but a higher risk of toxoplasmosis (adjusted relative risk, 1.81; 95 percent confidence interval, 1.12 to 2.94; P = 0.02). Among the 262 patients with serologic evidence of past exposure to Toxoplasma gondii, the relative risk of symptomatic toxoplasmosis was 2.37 times higher in those assigned to pentamidine (95 percent confidence interval, 1.3 to 4.4; P = 0.006). More patients discontinued dapsone-pyrimethamine than pentamidine because of toxicity (42 vs. 3; P<0.001). Survival was similar in the two groups.

Conclusions For primary prevention of P. carinii pneumonia, dapsone-pyrimethamine is as effective, though not as well tolerated, as aerosolized pentamidine. Dapsone-pyrimethamine also prevents first episodes of toxoplasmosis.

Source Information

From the Institut National de la Sante et de la Recherche Medicale, Unite 13, Paris (P.-M.G., R.L., Claude Gaudebout, P.J.); the Pharmacie (A.C.) and the Services des Maladies Infectieuses et Tropicales (R.O., A.G.S., Christiane Gaudebout, E.B., J.-P.C.), Hopital Bichat-Claude Bernard, Paris; the Service des Maladies Infectieuses et Tropicales, Hopital Saint Louis, Paris (T.L.); and the Service de Medecine Interne, Clamart (F.B.) -- all in France. The members of the PRIO (Prevention des Infections Opportunistes) Study Group are listed in the Appendix.

Address reprint requests to Dr. Girard at INSERM, Unite 13, 190 Blvd. MacDonald, 75019 Paris, France.

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