Once-weekly administration of dapsone/pyrimethamine vs. aerosolized pentamidine as combined prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis in human immunodeficiency virus-infected patients.
To evaluate combined prophylaxis for Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis, 533 patients with symptomatic human immunodeficiency virus infection and/or CD4 lymphocyte counts of < 200/microL were randomized to receive dapsone/pyrimethamine (200/75 mg once weekly) or aerosolized pentamidine (300 mg every 4 weeks). The median CD4 lymphocyte count was 110/microL; 47.5% were seropositive for toxoplasma antibodies. The median duration of follow-up was 483 days. In the intent-to-treat analysis, 12 cases of PCP and 14 of toxoplasmic encephalitis occurred in the dapsone/pyrimethamine group and 13 and 20 cases, respectively, in the aerosolized pentamidine group (adjusted relative risk for toxoplasmosis, 0.56; P = .10). However, only two of the 14 cases of toxoplasmic encephalitis in the dapsone/pyrimethamine group developed during actual treatment. The mortality among the two groups was similar. Dapsone/pyrimethamine was not tolerated by 30% of participants. A subanalysis of 240 matched, tolerant patients yielded a relative risk for toxoplasmosis of 0.21 (P = .014), a result favoring the use of dapsone/pyrimethamine. Dapsone/pyrimethamine was as effective as aerosolized pentamidine as prophylaxis for PCP and significantly reduced the incidence of toxoplasmic encephalitis among those participants who tolerated it.
Opravil
M
M
University Hospital of Zurich, Switzerland.
Hirschel
B
B
Lazzarin
A
A
Heald
A
A
Pechère
M
M
Rüttimann
S
S
Iten
A
A
von Overbeck
J
J
Oertle
D
D
Praz
G
G
D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology / Q000517:prevention & control*; D000280:Administration, Inhalation; D000328:Adult; D000818:Animals; D003622:Dapsone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004660:Encephalitis / Q000150:complications / Q000453:epidemiology / Q000469:parasitology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010419:Pentamidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D011739:Pyrimethamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016781:Toxoplasmosis, Cerebral / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*
D010419:Pentamidine; D003622:Dapsone; D011739:Pyrimethamine