Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS

Objective: To assess the safety, tolerance and activity of increasing doses of azithromycin in combination with pyrimethamine for the treatment of tox oplasmic encephalitis (TE) in patients with AIDS. Design: A phase I/II dose-escalation study of oral azithromycin in combinat ion with pyrimethamine. Setting: Eight clinical sites in the United States. Patients: Forty-two adult HIV-infected patients with confirmed or presumed acute TE. Methods: Patients were enrolled into three successive cohorts receiving azi thromycin 900, 1200 and 1500 mg a day with pyrimethamine as induction thera py. The induction period was 6 weeks followed by 24 weeks of maintenance th erapy. Main outcome measures: Patient response was evaluated clinically and radiol ogically. Results: Of the 30 evaluable patients, 20 (67%) responded to therapy during the induction period. Ten experienced disease progression. Of the 15 patie nts who received maintenance therapy, seven (47%) relapsed. Six patients di scontinued treatment during the induction period as a result of reversible toxicities. Treatment-terminating adverse events occurred most frequently a mong the patients receiving the 1500 mg dose. Conclusion: The combination of azithromycin (900-1200 mg a day) and pyrimet hamine may be useful as an alternative therapy for TE among patients intole rant of sulfonamides and clindamycin, but maintenance therapy with this com bination was associated with a high relapse rate. The combination was safe, but low-grade adverse events were common. (C) 2001 Lippincott Williams & W ilkins.