What is the first‑line treatment for HSV‑1 esophagitis in an immunocompromised adult (e.g., HIV/AIDS, solid‑organ or hematopoietic‑cell transplant, or receiving chemotherapy)?

Treatment of HSV-1 Esophagitis in Immunocompromised Adults

Intravenous acyclovir 5-10 mg/kg every 8 hours is the first-line treatment for HSV-1 esophagitis in immunocompromised adults, continuing for 7-14 days until clinical resolution is achieved. 1

Initial Treatment Approach

Standard Intravenous Therapy

• Administer IV acyclovir 5-10 mg/kg every 8 hours for immunocompromised patients with HSV esophagitis, as this achieves adequate plasma levels to control viral replication in severely compromised hosts 1
• Continue treatment for 7-14 days minimum, extending therapy until complete clinical resolution and healing of esophageal lesions 1
• The higher end of the dosing range (10 mg/kg) should be used for severely immunocompromised patients or those with disseminated disease 1

Route Selection Rationale

• Intravenous therapy is mandatory rather than oral therapy because immunocompromised patients may have impaired absorption, more severe disease, and higher risk of dissemination 1
• Oral acyclovir is not recommended as first-line therapy for esophagitis in immunocompromised patients due to inadequate bioavailability for visceral HSV involvement 1

Diagnostic Confirmation

Endoscopic Evaluation

• Definitive diagnosis requires endoscopy with biopsy showing histologic evidence of multinucleated giant cells with intranuclear viral inclusions and culture confirmation 1
• Laboratory confirmation is essential in immunocompromised patients, as clinical diagnosis alone is unreliable in this population 1

Treatment Duration and Monitoring

Clinical Endpoints

• Continue IV acyclovir until all esophageal lesions have healed, not just for an arbitrary 7-day period 1
• Immunocompromised patients may require prolonged treatment beyond 14 days if lesions persist or healing is delayed 1
• Consider repeat endoscopy to document healing before discontinuing therapy in severely immunocompromised patients 1

Renal Function Monitoring

• Dose adjustment based on creatinine clearance is mandatory in patients with renal insufficiency, as acyclovir is primarily excreted by the kidney 1, 2
• Monitor renal function at initiation and once or twice weekly during treatment with IV acyclovir 2
• Primary toxicities include phlebitis, renal toxicity, nausea, vomiting, and rash 1

Management of Treatment Failure

Acyclovir-Resistant HSV

• If lesions fail to improve within 7-10 days of appropriate therapy, suspect acyclovir resistance and obtain viral culture with susceptibility testing 1
• For documented or suspected acyclovir resistance, switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution 3
• All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir 3

Special Considerations by Patient Population

HIV/AIDS Patients

• Patients with advanced HIV (CD4 <200/mm³) are at highest risk for severe HSV esophagitis and require aggressive IV therapy 1
• Consider long-term suppressive therapy after acute treatment if CD4 remains low 1

Solid Organ Transplant Recipients

• Maintain IV acyclovir therapy throughout the acute episode, with consideration for temporary reduction in immunosuppressive medications if clinically feasible 4
• Transition to oral suppressive therapy may be considered after complete healing 4

Hematopoietic Cell Transplant Recipients

• These patients require the full 10 mg/kg every 8 hours dosing due to profound immunosuppression 1
• Extended treatment duration is often necessary until immune reconstitution occurs 1

Chemotherapy Patients

• Continue IV acyclovir throughout neutropenic period and until esophageal healing is documented 1
• Consider HSV prophylaxis during future chemotherapy cycles if patient experienced HSV esophagitis 5

Critical Pitfalls to Avoid

• Never use oral acyclovir as initial therapy for HSV esophagitis in immunocompromised patients—this is inadequate for visceral involvement 1
• Do not discontinue therapy at exactly 7 days if lesions have not completely healed 1
• Avoid topical antivirals, as they are substantially less effective than systemic therapy 6
• Do not assume CMV prophylaxis covers HSV if the patient is receiving letermovir—separate HSV coverage is required 5
• Never delay treatment while awaiting biopsy results if clinical suspicion is high—empiric IV acyclovir should be started immediately 1

Transition to Oral Therapy

• Once clinical improvement is documented and the patient can tolerate oral intake, consider transitioning to oral acyclovir 400 mg 3-5 times daily or valacyclovir 500-1000 mg twice daily to complete the treatment course 1
• Ensure complete healing before discontinuing all antiviral therapy 1