Thrice-weekly cotrimoxazole is better than weekly dapsone-pyrimethamine for the primary prevention of Pneumocystis carinii pneumonia in HIV-infected patients.
OBJECTIVE
To compare the efficacy and safety of two intermittent regimens for the simultaneous primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis in HIV-infected patients.


METHODS
Prospective randomized open trial.


METHODS
HIV outpatient clinic of an Infectious Disease Service and a 1000-bed university teaching hospital.


METHODS
A total of 166 HIV-infected patients with a CD4 cell count < 200 x 10(6)/l or a CD4 percentage < 20%, without previous PCP or toxoplasmosis.


METHODS
Patients were randomized to oral (1) cotrimoxazole [160 mg trimethoprim (TMP) and 800 mg sulphamethoxazole (SMX)] twice a day on Mondays, Wednesdays and Fridays (n = 81), or (2) dapsone (100 mg) plus pyrimethamine (25 mg) (DP) once a week (n = 85).


METHODS
Clinical and biological evaluation was performed every 30-60 days. End-points were PCP, toxoplasmosis and death. Adverse reactions were considered as defined in the protocol.


RESULTS
After a mean follow-up of 380 days, intention-to-treat analysis revealed that DP patients had a higher rate of PCP [13 out of 85 (15.2%) versus three out of 81 (3.7%); P = 0.01]. The cumulative rates of PCP at 12 and 24 months were 5 and 42% for DP patients and 3 and 10% for TMP-SMX patients, respectively (Mantel-Cox, P = 0.0007). Of the 29 patients who died during follow-up, 14 were in the TMP-SMX group and 15 in the DP group (not significant). Two patients in the TMP-SMX group and three in the DP group developed toxoplasmosis (not significant). Adverse reactions were common (66.7% of TMP-SMX patients and 42.4% of DP patients; P = 0.001). However, only 12.3% of TMP-SMX patients and 2.3% of DP patients (P = 0.01) had to discontinue therapy because of toxicity.


CONCLUSIONS
At the given doses, DP was inferior to TMP-SMX in preventing first episodes of PCP. Although more patients and a longer follow-up are required, the regimens appeared to prevent toxoplasmosis equally well.
Podzamczer
D
D
Infectious Disease Service, Ciudad Sanitaria de Bellvitge, Barcelona, Spain.
Santín
M
M
Jimenez
J
J
Casanova
A
A
Bolao
F
F
Gudiol
G R
GR
D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000328:Adult; D003622:Dapsone / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control*; D011446:Prospective Studies; D011739:Pyrimethamine / Q000008:administration & dosage / Q000009:adverse effects; D014123:Toxoplasmosis / Q000517:prevention & control; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000009:adverse effects
D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D003622:Dapsone; D011739:Pyrimethamine