Aerosolized pentamidine, cotrimoxazole and dapsone-pyrimethamine for primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis.
OBJECTIVE
To investigate the efficacy and safety of three regimens for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) and to evaluate their effect on survival in patients with HIV infection.


METHODS
Randomized, open label, prospective trial.


METHODS
A single Infectious Diseases Department in Italy.


METHODS
HIV-infected patients (n = 197) with a CD4 count < 200 x 10(6)/l and without previous PCP or TE.


METHODS
Patients were randomly assigned to receive (1) aerosolized pentamidine (AP; 300 mg monthly), (2) cotrimoxazole (CTX; 160 mg trimethoprim and 800 mg sulfamethoxazole every other day), or (3) dapsone-pyrimethamine (DP; 100 mg weekly dapsone and 25 mg biweekly pyrimethamine).


METHODS
PCP, TE, death, and drug-limiting toxicity. Considering difference in PCP occurrence the trial was interrupted on June 1992. Observation was prolonged until June 1994 for TE and survival.


RESULTS
Intention-to-treat analysis yielded PCP rates of 10.2 per 100 person-years in the AP, 2.0 in the CTX, and 32.1 in the DP group [adjusted relative risk of DP versus CTX: 17.5; 95% confidence interval (CI), 2.2-139.6; P = 0.007]. TE rates in patients with positive Toxoplasma serology were 25.6 per 100 person-years in the AP, 8.9 in the CTX and 9.4 in the DP group. In 'on treatment' analysis, no episode of TE developed in the DP group, and rates were 34.7 per 100 person-years in the AP and 2.5 in the CTX group (AP versus CTX: P = 0.01; AP versus DP: P = 0.004). The adjusted risk of mortality for the DP group was 2.8 times that of the CTX group in the first part of the study (95% CI, 1.1-7.3; P = 0.037), and 1.8 times (95% CI, 1.1-2.9; P = 0.02) in the prolonged follow-up. No significant difference in the occurrence of serious adverse reactions was observed between the three treatment groups.


CONCLUSIONS
Intermittent CTX was more effective than low-dose DP and showed a slight but not significant advantage on AP for primary PCP prophylaxis. DP was associated with a shorter survival. Both CTX and DP resulted in a significant reduction in the risk of TE.
Antinori
A
A
Department of Infectious Diseases, Catholic University, Rome, Italy.
Murri
R
R
Ammassari
A
A
De Luca
A
A
Linzalone
A
A
Cingolani
A
A
Damiano
F
F
Maiuro
G
G
Vecchiet
J
J
Scoppettuolo
G
G
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000627:therapeutic use; D003622:Dapsone / Q000627:therapeutic use; D004660:Encephalitis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D010419:Pentamidine / Q000627:therapeutic use; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy*; D011739:Pyrimethamine; D016781:Toxoplasmosis, Cerebral / Q000188:drug therapy*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
D000890:Anti-Infective Agents; D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D010419:Pentamidine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D003622:Dapsone; D011739:Pyrimethamine