A 36-year-old man with poorly controlled HIV (CD4 28 cells/µL, not on ART) presents with 2 weeks of crampy abdominal pain, profuse watery diarrhea progressing to bloody diarrhea, fever, and 6 kg weight loss. Colonoscopy reveals deep, well-demarcated longitudinal serpiginous ulcers in the descending colon with patchy yellow-white pseudomembranes and submucosal hemorrhage. Biopsies from the **ulcer edges** show enlarged endothelial and stromal cells with characteristic "owl-eye" intranuclear inclusions surrounded by a clear halo, plus cytoplasmic basophilic inclusions. CMV PCR is positive. The diagnosis is **Cytomegalovirus colitis** as marked in position **B** of the diagram. What is the most appropriate initial management?

Question

Accepted Answer

D. Intravenous ganciclovir 5 mg/kg twice daily for 14–21 days plus reinitiation of antiretroviral therapy within 2 weeks. ## Why option 1 is correct

The clinical presentation—deep serpiginous ulcers with owl-eye intranuclear inclusions on biopsy, positive CMV PCR, and CD4 <50 cells/µL—is pathognomonic for CMV colitis. Per IDSA guidelines and Mandell 9e, first-line induction therapy is **intravenous ganciclovir 5 mg/kg twice daily for 14–21 days** (or until clinical and endoscopic resolution). Critically, **antiretroviral therapy must be reinitiated within 2 weeks** to restore CD4 count and prevent continued CMV progression; delaying ART risks ongoing end-organ disease, while starting too early risks immune reconstitution inflammatory syndrome (IRIS). This two-pronged approach—direct antiviral + immune reconstitution—is the standard of care for CMV end-organ disease in advanced HIV.

## Why each distractor is wrong

- **Option 2 (vancomycin + metronidazole)**: This is the regimen for *Clostridioides difficile* colitis (marked **A**), not CMV. C. difficile typically follows antibiotic exposure and presents with pseudomembranes on colonoscopy, but lacks the characteristic owl-eye inclusions and does not require ART reinitiation.

- **Option 3 (IV corticosteroids + mesalamine)**: This is appropriate for *ulcerative colitis* flare (marked **C**), an inflammatory bowel disease. Corticosteroids would be contraindicated in CMV colitis because they further suppress immunity and allow CMV replication to accelerate, worsening disease.

- **Option 4 (metronidazole + paromomycin)**: This is the regimen for *amebic colitis* (marked **D**) caused by *Entamoeba histolytica*, which presents with flask-shaped ulcers and trophozoites on stool microscopy, not owl-eye inclusions.

**High-Yield:** CMV colitis in advanced HIV requires **IV ganciclovir + prompt ART reinitiation**; owl-eye inclusions on ulcer-edge biopsy are diagnostic; CD4 <50 is the risk threshold.

[cite: IDSA HIV Opportunistic Infections Guidelines 2024; Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 9e]

Answer

A. Metronidazole 750 mg three times daily plus paromomycin 25–35 mg/kg/day in three divided doses

Answer

B. Intravenous corticosteroids (methylprednisolone 1 g daily) plus mesalamine enemas

Answer

C. Oral vancomycin 125 mg four times daily for 10 days followed by metronidazole

Explanation

Why option 1 is correct

Why each distractor is wrong

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