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

AIDS. 2001 Mar 30;15(5):583-9. doi: 10.1097/00002030-200103300-00007.


Objective: To assess the safety, tolerance and activity of increasing doses of azithromycin in combination with pyrimethamine for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS.

Design: A phase I/II dose-escalation study of oral azithromycin in combination 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 azithromycin 900, 1200 and 1500 mg a day with pyrimethamine as induction therapy. The induction period was 6 weeks followed by 24 weeks of maintenance therapy.

Main outcome measures: Patient response was evaluated clinically and radiologically.

Results: Of the 30 evaluable patients, 20 (67%) responded to therapy during the induction period. Ten experienced disease progression. Of the 15 patients who received maintenance therapy, seven (47%) relapsed. Six patients discontinued treatment during the induction period as a result of reversible toxicities. Treatment-terminating adverse events occurred most frequently among the patients receiving the 1500 mg dose.

Conclusion: The combination of azithromycin (900-1200 mg a day) and pyrimethamine may be useful as an alternative therapy for TE among patients intolerant of sulfonamides and clindamycin, but maintenance therapy with this combination was associated with a high relapse rate. The combination was safe, but low-grade adverse events were common.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / diagnostic imaging
  • AIDS-Related Opportunistic Infections / drug therapy*
  • Adult
  • Animals
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Antiprotozoal Agents / adverse effects
  • Antiprotozoal Agents / therapeutic use*
  • Azithromycin / adverse effects
  • Azithromycin / therapeutic use*
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Encephalitis / diagnostic imaging
  • Encephalitis / drug therapy*
  • Female
  • Humans
  • Male
  • Pyrimethamine / adverse effects
  • Pyrimethamine / therapeutic use*
  • Radiography
  • Toxoplasma
  • Toxoplasmosis / diagnostic imaging
  • Toxoplasmosis / drug therapy*
  • Treatment Outcome
  • United States


  • Anti-Bacterial Agents
  • Antiprotozoal Agents
  • Azithromycin
  • Pyrimethamine