Posaconazole for the Treatment of Azole-Refractory Oropharyngeal and Esophageal Candidiasis in Subjects with HIV Infection

• Published in: Clinical infectious diseases 2007-02, Vol.44 (4), p.607-614
• Main Authors: Skiest, Daniel J., Vazquez, Jose A., Anstead, Gregory M., Graybill, John R., Reynes, Jacques, Ward, Douglas, Hare, Roberta, Boparai, Navdeep, Isaacs, Randi
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; AIDS; AIDS-Related Opportunistic Infections - diagnosis; AIDS-Related Opportunistic Infections - drug therapy; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungals; Azoles; Biological and medical sciences; Candidiasis; Candidiasis - diagnosis; Candidiasis - drug therapy; Candidiasis, Oral - diagnosis; Candidiasis, Oral - drug therapy; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Fungal; Drug therapy; Drugs; Esophageal Diseases - diagnosis; Esophageal Diseases - drug therapy; Esophagus; Female; Fluconazole - administration & dosage; Fluconazole - adverse effects; Follow-Up Studies; HIV; HIV infections; HIV/AIDS; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infections; Infectious diseases; Itraconazole - administration & dosage; Itraconazole - adverse effects; Male; Medical sciences; Middle Aged; Mycology; Pharmacology. Drug treatments; Probability; Relapse; Response rates; Severity of Illness Index; Symptoms; Transponders; Treatment Failure; Treatment Outcome; Triazoles - administration & dosage; Triazoles - adverse effects; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/511039

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 fluconazole 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 fluconazole- 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 fluconazole, 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.