Dose-escalation, phase 1/11 study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS

Jeffrey M. Jacobson, Richard Hafner, Jack Remington, Charles Farthing, Jeanne Holden-Wiltse, Elizabeth M. Bosler, Carol Harris, Dushyantha T Jayaweera, Clemente Roque, Benjamin J. Luft

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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 1/11 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 1500mg 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.

Original languageEnglish
Pages (from-to)583-589
Number of pages7
JournalAIDS
Volume15
Issue number5
DOIs
StatePublished - Mar 30 2001

Fingerprint

Pyrimethamine
Azithromycin
Encephalitis
Acquired Immunodeficiency Syndrome
Therapeutics
Clindamycin
Sulfonamides
Complementary Therapies
Disease Progression
Outcome Assessment (Health Care)
HIV
Safety
Recurrence

Keywords

  • AIDS
  • Azithromycin
  • HIV
  • Pyrimethamine
  • Toxoplasmic encephalitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Jacobson, J. M., Hafner, R., Remington, J., Farthing, C., Holden-Wiltse, J., Bosler, E. M., ... Luft, B. J. (2001). Dose-escalation, phase 1/11 study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS. AIDS, 15(5), 583-589. https://doi.org/10.1097/00002030-200103300-00007

Dose-escalation, phase 1/11 study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS. / Jacobson, Jeffrey M.; Hafner, Richard; Remington, Jack; Farthing, Charles; Holden-Wiltse, Jeanne; Bosler, Elizabeth M.; Harris, Carol; Jayaweera, Dushyantha T; Roque, Clemente; Luft, Benjamin J.

In: AIDS, Vol. 15, No. 5, 30.03.2001, p. 583-589.

Research output: Contribution to journalArticle

Jacobson, JM, Hafner, R, Remington, J, Farthing, C, Holden-Wiltse, J, Bosler, EM, Harris, C, Jayaweera, DT, Roque, C & Luft, BJ 2001, 'Dose-escalation, phase 1/11 study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS', AIDS, vol. 15, no. 5, pp. 583-589. https://doi.org/10.1097/00002030-200103300-00007
Jacobson, Jeffrey M. ; Hafner, Richard ; Remington, Jack ; Farthing, Charles ; Holden-Wiltse, Jeanne ; Bosler, Elizabeth M. ; Harris, Carol ; Jayaweera, Dushyantha T ; Roque, Clemente ; Luft, Benjamin J. / Dose-escalation, phase 1/11 study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS. In: AIDS. 2001 ; Vol. 15, No. 5. pp. 583-589.
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abstract = "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 1/11 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 1500mg 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.",
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