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Acyclovir-resistant mucocutaneous herpes simplex virus infection in advanced HIV — ABIM Board MCQ

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HardAntiviral TherapyAcyclovir-resistant mucocutaneous herpes simplex virus infection in advanced HIVABIM Board

A 44-year-old man with advanced HIV infection is hospitalized with multiple deep, painful perianal ulcers. His CD4 count is 28 cells/mm3, and plasma HIV RNA is 186,000 copies/mL. A lesion nucleic acid amplification test is positive for herpes simplex virus type 2. Valacyclovir, 1 g orally twice daily, is started. During 10 days of inpatient treatment, every dose is administered, but the ulcers enlarge and new lesions appear. He has no fever, hepatitis, neurologic findings, or evidence of another ulcerative infection. His serum creatinine is 0.9 mg/dL, and serum potassium, magnesium, and calcium concentrations are normal. Which of the following is the most appropriate next antiviral management?

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Correct answer: A — Obtain a viral culture for susceptibility testing and start intravenous foscarnet

The absence of any clinical response after 10 days of reliably administered anti-HSV therapy in a patient with advanced immunosuppression should prompt suspicion for acyclovir-resistant HSV. A lesion viral culture should be obtained for phenotypic susceptibility testing; molecular resistance testing is not routinely available. Treatment should not be delayed while susceptibility results are pending. Intravenous foscarnet, typically 40 mg/kg every 8–12 hours until clinical response, is preferred therapy, with close monitoring of renal function and electrolytes because of nephrotoxicity and mineral abnormalities. ([clinicalinfo.hiv-stage.od.nih.gov](https://clinicalinfo.hiv-stage.od.nih.gov/sites/default/files/guidelines/documents/adult-adolescent-oi/herpes-simplex-virus-adult-adolescent-oi.pdf?utm_source=openai)) Continuing valacyclovir is inappropriate because acyclovir-resistant isolates are also resistant to valacyclovir. Most are also resistant to famciclovir, making an empiric switch unreliable. Intravenous acyclovir is appropriate for severe susceptible HSV or visceral/CNS disease, but increasing exposure does not overcome established acyclovir resistance. Intravenous cidofovir has activity against resistant HSV but is a less-supported alternative rather than preferred therapy and carries substantial nephrotoxicity. Thus, the combination of profound immunosuppression, verified adherence, progressive lesions after the 7–10-day failure threshold, and expected cross-resistance identifies foscarnet as the single best treatment.

Reference: Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV—Herpes Simplex Virus (Current guideline PDF indexed in 2026) — https://clinicalinfo.hiv-stage.od.nih.gov/sites/default/files/guidelines/documents/adult-adolescent-oi/herpes-simplex-virus-adult-adolescent-oi.pdf CDC STI Treatment Guidelines—Genital Herpes (Last reviewed September 21, 2022) — https://www.cdc.gov/std/treatment-guidelines/herpes.htm