Posaconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection

Daniel J. Skiest, Jose Antonio Vazquez, Gregory M. Anstead, John R. Graybill, Jacques Reynes, Douglas Ward, Roberta Hare, Navdeep Boparai, Randi Isaacs

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Background. We evaluated the efficacy and safety of oral posaconazole for human immunodeficiency virus (HIV)-infected subjects with oropharyngeal candidiasis (OPC) and/or esophageal candidiasis (EC) who were clinically refractory to treatment with oral fiuconazole or itraconazole. Methods. Subjects with confirmed OPC or EC who did not improve after receiving standard courses of fluconazole or itraconazole treatment were eligible for study enrollment. Subjects received either oral posaconazole (400 mg twice daily) for 3 days followed by oral posaconazole (400 mg once daily) for 25 days (regimen A; 103 patients) or oral posaconazole (400 mg twice daily) for 28 days (regimen B; 96 patients). The primary end point was cure or improvement after 28 days. Primary efficacy analyses were performed on the subset of treated subjects with refractory disease (e.g., baseline culture positive for fiuconazole- or itraconazole-resistant Candida species or persistent or progressive clinical signs or symptoms consistent with treatment failure). Results. Of the modified intent-to-treat population, 132 (75%) of 176 subjects achieved a clinical response to posaconazole treatment. Clinical response rates were similar between regimen A recipients (75.3%) and regimen B recipients (74.7%). Clinical responses occurred in 67 (73%) of 92 subjects with baseline isolates resistant to fiuconazole, 49 (74%) of 66 subjects with baseline isolates resistant to itraconazole, and 42 (74%) of 57 subjects with isolates resistant to both. Clinical response was achieved in 32 (74.4%) of 43 subjects with endoscopically documented EC. The most common treatment-related adverse events were diarrhea (11%), neutropenia (7%), flatulence (6%), and nausea (6%). Eight subjects (4%) discontinued therapy as a result of a treatment-related adverse event. Conclusions. Posaconazole offers a safe and effective treatment option for HIV-infected subjects with azole-refractory OPC and/or EC.

Original languageEnglish (US)
Pages (from-to)607-614
Number of pages8
JournalClinical Infectious Diseases
Volume44
Issue number4
DOIs
StatePublished - Feb 15 2007

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Azoles
Candidiasis
Virus Diseases
HIV
Itraconazole
Therapeutics
Flatulence
Fluconazole
posaconazole
Neutropenia
Treatment Failure
Candida
Nausea
Signs and Symptoms
Diarrhea
Safety
Population

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Posaconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection. / Skiest, Daniel J.; Vazquez, Jose Antonio; Anstead, Gregory M.; Graybill, John R.; Reynes, Jacques; Ward, Douglas; Hare, Roberta; Boparai, Navdeep; Isaacs, Randi.

In: Clinical Infectious Diseases, Vol. 44, No. 4, 15.02.2007, p. 607-614.

Research output: Contribution to journalArticle

Skiest, DJ, Vazquez, JA, Anstead, GM, Graybill, JR, Reynes, J, Ward, D, Hare, R, Boparai, N & Isaacs, R 2007, 'Posaconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection', Clinical Infectious Diseases, vol. 44, no. 4, pp. 607-614. https://doi.org/10.1086/511039
Skiest, Daniel J. ; Vazquez, Jose Antonio ; Anstead, Gregory M. ; Graybill, John R. ; Reynes, Jacques ; Ward, Douglas ; Hare, Roberta ; Boparai, Navdeep ; Isaacs, Randi. / Posaconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection. In: Clinical Infectious Diseases. 2007 ; Vol. 44, No. 4. pp. 607-614.
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abstract = "Background. We evaluated the efficacy and safety of oral posaconazole for human immunodeficiency virus (HIV)-infected subjects with oropharyngeal candidiasis (OPC) and/or esophageal candidiasis (EC) who were clinically refractory to treatment with oral fiuconazole or itraconazole. Methods. Subjects with confirmed OPC or EC who did not improve after receiving standard courses of fluconazole or itraconazole treatment were eligible for study enrollment. Subjects received either oral posaconazole (400 mg twice daily) for 3 days followed by oral posaconazole (400 mg once daily) for 25 days (regimen A; 103 patients) or oral posaconazole (400 mg twice daily) for 28 days (regimen B; 96 patients). The primary end point was cure or improvement after 28 days. Primary efficacy analyses were performed on the subset of treated subjects with refractory disease (e.g., baseline culture positive for fiuconazole- or itraconazole-resistant Candida species or persistent or progressive clinical signs or symptoms consistent with treatment failure). Results. Of the modified intent-to-treat population, 132 (75{\%}) of 176 subjects achieved a clinical response to posaconazole treatment. Clinical response rates were similar between regimen A recipients (75.3{\%}) and regimen B recipients (74.7{\%}). Clinical responses occurred in 67 (73{\%}) of 92 subjects with baseline isolates resistant to fiuconazole, 49 (74{\%}) of 66 subjects with baseline isolates resistant to itraconazole, and 42 (74{\%}) of 57 subjects with isolates resistant to both. Clinical response was achieved in 32 (74.4{\%}) of 43 subjects with endoscopically documented EC. The most common treatment-related adverse events were diarrhea (11{\%}), neutropenia (7{\%}), flatulence (6{\%}), and nausea (6{\%}). Eight subjects (4{\%}) discontinued therapy as a result of a treatment-related adverse event. Conclusions. Posaconazole offers a safe and effective treatment option for HIV-infected subjects with azole-refractory OPC and/or EC.",
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T1 - Posaconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection

AU - Skiest, Daniel J.

AU - Vazquez, Jose Antonio

AU - Anstead, Gregory M.

AU - Graybill, John R.

AU - Reynes, Jacques

AU - Ward, Douglas

AU - Hare, Roberta

AU - Boparai, Navdeep

AU - Isaacs, Randi

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N2 - Background. We evaluated the efficacy and safety of oral posaconazole for human immunodeficiency virus (HIV)-infected subjects with oropharyngeal candidiasis (OPC) and/or esophageal candidiasis (EC) who were clinically refractory to treatment with oral fiuconazole or itraconazole. Methods. Subjects with confirmed OPC or EC who did not improve after receiving standard courses of fluconazole or itraconazole treatment were eligible for study enrollment. Subjects received either oral posaconazole (400 mg twice daily) for 3 days followed by oral posaconazole (400 mg once daily) for 25 days (regimen A; 103 patients) or oral posaconazole (400 mg twice daily) for 28 days (regimen B; 96 patients). The primary end point was cure or improvement after 28 days. Primary efficacy analyses were performed on the subset of treated subjects with refractory disease (e.g., baseline culture positive for fiuconazole- or itraconazole-resistant Candida species or persistent or progressive clinical signs or symptoms consistent with treatment failure). Results. Of the modified intent-to-treat population, 132 (75%) of 176 subjects achieved a clinical response to posaconazole treatment. Clinical response rates were similar between regimen A recipients (75.3%) and regimen B recipients (74.7%). Clinical responses occurred in 67 (73%) of 92 subjects with baseline isolates resistant to fiuconazole, 49 (74%) of 66 subjects with baseline isolates resistant to itraconazole, and 42 (74%) of 57 subjects with isolates resistant to both. Clinical response was achieved in 32 (74.4%) of 43 subjects with endoscopically documented EC. The most common treatment-related adverse events were diarrhea (11%), neutropenia (7%), flatulence (6%), and nausea (6%). Eight subjects (4%) discontinued therapy as a result of a treatment-related adverse event. Conclusions. Posaconazole offers a safe and effective treatment option for HIV-infected subjects with azole-refractory OPC and/or EC.

AB - Background. We evaluated the efficacy and safety of oral posaconazole for human immunodeficiency virus (HIV)-infected subjects with oropharyngeal candidiasis (OPC) and/or esophageal candidiasis (EC) who were clinically refractory to treatment with oral fiuconazole or itraconazole. Methods. Subjects with confirmed OPC or EC who did not improve after receiving standard courses of fluconazole or itraconazole treatment were eligible for study enrollment. Subjects received either oral posaconazole (400 mg twice daily) for 3 days followed by oral posaconazole (400 mg once daily) for 25 days (regimen A; 103 patients) or oral posaconazole (400 mg twice daily) for 28 days (regimen B; 96 patients). The primary end point was cure or improvement after 28 days. Primary efficacy analyses were performed on the subset of treated subjects with refractory disease (e.g., baseline culture positive for fiuconazole- or itraconazole-resistant Candida species or persistent or progressive clinical signs or symptoms consistent with treatment failure). Results. Of the modified intent-to-treat population, 132 (75%) of 176 subjects achieved a clinical response to posaconazole treatment. Clinical response rates were similar between regimen A recipients (75.3%) and regimen B recipients (74.7%). Clinical responses occurred in 67 (73%) of 92 subjects with baseline isolates resistant to fiuconazole, 49 (74%) of 66 subjects with baseline isolates resistant to itraconazole, and 42 (74%) of 57 subjects with isolates resistant to both. Clinical response was achieved in 32 (74.4%) of 43 subjects with endoscopically documented EC. The most common treatment-related adverse events were diarrhea (11%), neutropenia (7%), flatulence (6%), and nausea (6%). Eight subjects (4%) discontinued therapy as a result of a treatment-related adverse event. Conclusions. Posaconazole offers a safe and effective treatment option for HIV-infected subjects with azole-refractory OPC and/or EC.

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