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Pyrimethamine alone as prophylaxis for cerebral toxoplasmosis in patients with advanced HIV infection

Monotherapie mit Pyrimethamin als Prophylaxe der cerebralen Toxoplasmose bei Patienten mit fortgeschrittener HIV-Infektion

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Summary

Prophylaxis for toxoplasma encephalitis was performed with pyrimethamine alone (50 mg daily) in 56 patients with advanced HIV infection. Thirty-eight patients were at high risk for toxoplasma encephalitis (CD4+ counts ≤200/ µl, and presence of serum IgG antibodies toToxoplasma gondii). The overall treatment period was 697 months (mean 12.5±12.1). During prophylaxis, only one patient developed toxoplasma encephalitis, four patients discontinued treatment due to adverse reactions. Steady state pyrimethamine plasma concentrations were measured by gas chromatography. Mean plasma level was 1,887±1,161 ng/ml, during liver enzyme-inducing comedication plasma levels were significantly (p=0.0001) reduced (1,488±884 ng/ml versus 1,978±1,196 ng/ml without comedication). All patients received a folinic acid supplement of 7.5 mg daily. Serum folate levels ranged from 5.7–105 (43.7±29.2) nmol/l; severe hematological side effects did not occur.

Zusammenfassung

Bei 56 Patienten mit fortgeschrittener HIV-Infektion wurde eine Prophylaxe der cerebralen Toxoplasmose mit Pyrimethamin als Monotherapie in einer Dosierung von 50 mg täglich durchgeführt. 38 dieser Patienten wiesen ein hohes Risiko für die Entwicklung einer Toxoplasma-Encephalitis auf (CD4+-Zellen ≤200/µl und Nachweis von IgG-Antikörpern gegenToxoplasma gondii). Die gesamte Behandlungsdauer betrug 697 Monate (im Mittel 12,5±12,1). Während der Prophylaxe entwickelte lediglich ein Patient eine cerebrale Toxoplasmose, vier Patienten brachen die Behandlung wegen Nebenwirkungen ab. Steady-state-Pyrimethamin-Plasmakonzentrationen wurden durch Gaschromatographie bestimmt. Der mittlere Plasmaspiegel betrug 1.887±1.161 ng/ml, während einer Leberenzym-induzierenden Komedikation wurden signifikant (p=0,0001) verminderte (1.488±884 ng/ml vs. 1.978±1.196 ng/ml ohne Komedikation) Plasmakonzentrationen gemessen. Alle Patienten erhielten additiv 7,5 mg Folinsäure pro Tag. Die gemessenen Serum-Folsäurespiegel schwankten zwischen 5,7 und 105 (43,7±29,2) nmol/l, schwerwiegende hämatologische Nebenwirkungen traten hierunter nicht auf.

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Klinker, H., Langmann, P. & Richter, E. Pyrimethamine alone as prophylaxis for cerebral toxoplasmosis in patients with advanced HIV infection. Infection 24, 324–327 (1996). https://doi.org/10.1007/BF01743370

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