Aerosolized pentamidine, cotrimoxazole and dapsone-pyrimethamine for primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis

Andrea Antinori, Rita Murri, Adriana Ammassari, Andrea De Luca, Angela Linzalone, Antonella Cingolani, Fernando Damiano, Giuseppe Maiuro, Jacopo Vecchiet, Giancarlo Scoppettuolo, Enrica Tamburrini, Luigi Ortona

Research output: Contribution to journalArticlepeer-review

Abstract

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. Design: Randomized, open label, prospective trial. Setting: A single Infectious Diseases Department in Italy. Patients: HIV-infected patients (n = 197) with a CD4 count <200 x 106/l and without previous PCP or TE. Interventions: 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). Main outcome measures: 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.

Original languageEnglish
Pages (from-to)1343-1350
Number of pages8
JournalAIDS (London, England)
Volume9
Issue number12
Publication statusPublished - Dec 1995

Keywords

  • Aerosolized pentamidine
  • Cotrimoxazole
  • Dapsone-pyrimethamine
  • Pneumocystis carinii pneumonia prophylaxis
  • Toxoplasmic encephalitis prophylaxis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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