Twice-weekly pyrimethamine-sulfadoxine effectively prevents Pneumocystis carinii pneumonia relapse and toxoplasmic encephalitis in patients with AIDS.
OBJECTIVE
To evaluate the safety and efficacy of a fixed 25mg pyrimethamine--500mg sulfadoxine combination plus 15mg folinic acid given twice weekly for the prevention of relapses of Pneumocystis carinii pneumonia (PCP) and primary episodes of toxoplasmic encephalitis.


METHODS
Ninety-five HIV-infected patients with successfully treated PCP and without history of toxoplasmic encephalitis were enrolled between January 1990 and October 1995 in a single-arm open-label prospective study. No patient was receiving highly active antiretroviral treatment, including protease inhibitors or non-nucleoside reverse transcriptase inhibitors, while on study medication. Efficacy was analysed on an "as-treated" basis.


RESULTS
Five patients (5.3%) suffered a PCP relapse while on study medication, three of whom had been non-compliant. No relapse occurred in the first year. Probabilities of freedom from relapse were 0.96 after 24 months and 0.90 after 36 months. Of 69 patients positive for anti-toxoplasma IgG antibodies, one (1.5%) developed cerebral lesions compatible with toxoplasmic encephalitis after 50 months. Cutaneous allergic reactions were observed in 16 patients (16.8%) resulting in permanent discontinuation in six patients (6.3%). Two patients (2.1%) developed serious adverse reactions (Stevens-Johnson syndrome), both of whom had continued prophylaxis despite progressive hypersensitivity reactions.


CONCLUSIONS
The prophylactic regimen used is effective in preventing PCP relapses and toxoplasmic encephalitis. The regimen appears to be safe. Severe adverse events can likely be prevented by discontinuation of prophylaxis at the time allergic reactions are noted. Rechallenge frequently results in tolerance of the regimen. Efficacy and safety compare favourably with previously studied regimens. This simple prophylactic regimen may provide a convenient alternative for patients unable to tolerate approved regimens.
Department of Infectious Diseases, Charité (Campus Virchow-Klinikum), Humboldt-Universität zu Berlin, Germany.
D
D
Schürmann
F
F
Bergmann
H
H
Albrecht
J
J
Padberg
T
T
Grünewald
M
M
Behnsch
M
M
Grobusch
M
M
Vallée
T
T
Wünsche
B
B
Ruf
N
N
Suttorp
D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D004338:Drug Combinations; D004341:Drug Evaluation; D004342:Drug Hypersensitivity; D004660:Encephalitis / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control*; D011446:Prospective Studies; D011739:Pyrimethamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012449:Safety; D055502:Secondary Prevention; D013413:Sulfadoxine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016781:Toxoplasmosis, Cerebral / Q000517:prevention & control*
D000890:Anti-Infective Agents; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine