What is the recommended acyclovir (antiviral medication) prophylaxis regimen for immunocompromised cardiac transplant recipients to prevent herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections?

Acyclovir Prophylaxis in Cardiac Transplant Recipients

Primary Recommendation

Cardiac transplant recipients who are HSV-seropositive should receive acyclovir prophylaxis (or valacyclovir/famciclovir) starting at transplantation and continuing for at least 1 year post-transplant, with consideration for extension if ongoing immunosuppression is required. 1

While the available guidelines primarily address hematopoietic cell transplant recipients rather than cardiac transplant recipients specifically, the principles of antiviral prophylaxis apply to all solid organ transplant populations given similar immunosuppression-related risks. 2

HSV Prophylaxis Strategy

Who Requires Prophylaxis

• HSV-seropositive cardiac transplant recipients require prophylaxis, as without it, 60-80% of seropositive immunosuppressed patients experience HSV reactivation 1
• HSV-seronegative recipients do not require acyclovir prophylaxis regardless of donor serostatus 3
• Pre-transplant serologic testing for anti-HSV IgG is mandatory to guide prophylaxis decisions 3

Recommended Agents and Dosing

First-line options (choose one): 3, 1

• Acyclovir 400 mg PO twice daily
• Valacyclovir 500 mg PO twice daily
• Famciclovir 250 mg PO twice daily

For acyclovir-resistant HSV: Foscarnet 40 mg/kg IV every 8 hours becomes necessary for all future prophylaxis 4

Duration of Prophylaxis

Standard duration: At least 1 year post-transplant 3, 5, 6

Extended prophylaxis beyond 1 year is indicated for: 3, 1

• Patients requiring ongoing systemic immunosuppression
• Patients with history of frequent HSV reactivations pre-transplant
• Patients who develop HSV reactivation requiring treatment (prophylaxis needed during all future immunosuppressive episodes)

The evidence demonstrates that 1-year prophylaxis provides persistent benefit after discontinuation without rebound VZV disease 6. Long-term prophylaxis beyond 1 year in patients on continued immunosuppression further reduces disease incidence 6.

VZV Prophylaxis Strategy

Rationale for Extended Coverage

The same acyclovir regimen used for HSV prophylaxis is also effective against VZV 3. VZV disease carries substantial morbidity and mortality in immunosuppressed patients 3.

Duration Considerations

• Acyclovir prophylaxis for at least 1 year significantly reduces VZV disease (risk ratio 0.38) 5
• Both low-dose (<400 mg/day) and standard-dose acyclovir are effective 5, 7
• Stopping prophylaxis at engraftment results in 25.8% cumulative incidence of VZV disease at 1 year, compared to 0% when continued beyond 1 year 7

VZV-Seronegative Patients

• Must strictly avoid contact with anyone with active VZV infection or reactivation 3
• Should receive VZV immunoglobulin rapidly after exposure to potentially infected persons 3
• VZV-IgG provides protection for 30 days and requires renewal after subsequent exposures 3

Important Clinical Considerations

When to Discontinue or Modify Prophylaxis

Discontinue acyclovir when: 3

• CMV prophylaxis or treatment with ganciclovir or foscarnet is initiated (both agents are active against HSV)

Continue separate HSV prophylaxis when: 3, 1, 4

• Receiving letermovir for CMV prophylaxis (letermovir lacks HSV activity)

Consequences of HSV Reactivation Without Prophylaxis

HSV reactivation causes: 1

• Significant mucosal damage
• Increased pain
• Limited ability to maintain oral hydration and nutrition
• Increased risk of bacterial and fungal superinfections

Managing Acyclovir Resistance

Suspect resistance when: Lesions persist despite standard acyclovir therapy 4

Treatment approach: 4

• Foscarnet 40 mg/kg IV every 8 hours for active infection
• All acyclovir-resistant strains are also resistant to valacyclovir and most to famciclovir
• Topical cidofovir gel 1% once daily for 5 days for accessible mucocutaneous lesions

Once resistance develops: Patient requires foscarnet for all future prophylaxis during immunosuppression 4

Common Pitfalls to Avoid

• Do not extend prophylaxis to day 100 only in cardiac transplant recipients—the evidence supports at least 1 year duration given ongoing immunosuppression 3, 5, 6
• Do not assume CMV prophylaxis covers all herpes viruses—letermovir requires separate HSV prophylaxis 3, 1, 4
• Do not use acyclovir for CMV prophylaxis—it has failed to prevent CMV disease 3
• Do not give prophylaxis to HSV-seronegative patients—it provides no benefit 3