A 42-year-old man with a history of AIDS comes to the office due to 2 weeks of painful swallowing. A week ago, the patient was prescribed oral fluconazole for these symptoms, but the pain has worsened despite taking the medication as indicated. Laboratory testing from a previous office visit shows a CD4 count of 42/mm³ and viral load of 300,000 copies/mL. Endoscopy reveals multiple large, linear ulcers in the distal esophagus. A biopsy of the abnormal mucosa shows tissue destruction and the presence of intranuclear and intracytoplasmic inclusions. Which of the following is the most appropriate pharmacotherapy for this patient?

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11ec25c8_d448_7d7b_bc81_b34f94df4add_MD0003_00 Patients with AIDS are at high risk for esophageal infections. They typically present with painful swallowing and retrosternal burning. The leading pathogen (~65%) is Candida albicans, which is generally suspected in those with mild pain and concurrent oral thrush. Because empiric treatment with oral fluconazole is curative, the presence of persistent/progressive symptoms on empiric therapy generally necessitates upper gastrointestinal endoscopy to evaluate for other common infectious (eg, cytomegalovirus [CMV], herpes simplex virus [HSV]) and noninfectious (eg, aphthous ulcers) causes. CMV esophagitis typically causes large, linear ulcerations in the distal esophagus; histopathology will reveal intranuclear and intracytoplasmic inclusions. The treatment of choice is intravenous ganciclovir. In contrast, herpes simplex esophagitis usually causes well-circumscribed lesions with a round/ovoid, "volcano-like" appearance (most patients also have concurrent orolabial herpetic lesions); histopathology will show ballooning degeneration and eosinophilic intranuclear inclusions. Although acyclovir treats HSV, it is not active against CMV because the virus does not encode the thymidine kinase enzyme needed to convert acyclovir to its active form (Choice A). well-circumscribed lesions (Choice C) Pentamidine is used for the prevention and treatment of Pneumocystis pneumonia in patients with advanced HIV who cannot tolerate trimethoprim-sulfamethoxazole. It has no role in the treatment of viral esophagitis. (Choice D) Prednisone is used to treat recurrent aphthous ulcers that have not responded to other treatments, such as topical corticosteroids. Aphthous ulcers have nonspecific histologic findings; the intracellular inclusions described here would not be consistent with this diagnosis. (Choice E) Candidiasis resistant to fluconazole may be treated with voriconazole, an echinocandin (eg, caspofungin), or amphotericin. This patient has typical endoscopic/biopsy findings for CMV, and the absence of thrush or typical white esophageal exudates makes candidal esophagitis less likely. Educational objective: Patients with AIDS who have odynophagia and visible oral thrush likely have candidal esophagitis and should receive 1-2 weeks of empiric oral fluconazole therapy. If symptoms persist and/or no thrush is apparent, endoscopy with biopsy is generally performed. Cytomegalovirus esophagitis is characterized by large, linear ulcers and intranuclear/intracytoplasmic inclusions; it is treated with ganciclovir. Herpes simplex esophagitis is characterized by small, well-circumscribed, round/ovoid ulcers and intranuclear inclusions; it is treated with acyclovir.

A 42-Year-Old Man with a History of AIDS Comes to the Office