HSV Prophylaxis in the Setting of Resistance

Understanding Acyclovir Resistance

The Centers for Disease Control and Prevention recommends that for acyclovir-resistant HSV, foscarnet 40 mg/kg IV every 8 hours is the treatment of choice, and once resistance develops, patients require foscarnet for all future prophylaxis during periods of immunosuppression 1, 2
All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir due to shared mechanisms of action targeting viral DNA polymerase 1, 2
Resistance should be suspected when lesions persist despite standard acyclovir therapy 1, 2

The National Comprehensive Cancer Network recommends topical cidofovir gel 1% applied once daily for 5 consecutive days for accessible mucocutaneous lesions 1, 2

The National Comprehensive Cancer Network suggests that once a patient develops acyclovir-resistant HSV requiring treatment, they need alternative prophylaxis (foscarnet) during all future episodes of neutropenia or immunosuppression 3, 4
Standard acyclovir prophylaxis (acyclovir 400 mg PO twice daily, valacyclovir 500 mg PO twice daily, or famciclovir 250 mg PO twice daily) is contraindicated in patients with documented resistance 3, 4
For patients receiving CMV prophylaxis with ganciclovir or foscarnet, additional HSV prophylaxis is unnecessary as these agents cover HSV 3, 4
However, patients on letermovir for CMV require separate HSV prophylaxis as letermovir lacks HSV activity 3, 4

The Centers for Disease Control and Prevention recommends higher doses of acyclovir (400 mg PO 3-5 times daily) for immunocompromised patients 1, 2
Famciclovir 500 mg twice daily has demonstrated efficacy in reducing recurrences and subclinical shedding in HIV patients 1, 2
Valacyclovir doses of 8 g/day are contraindicated due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura 1, 2
Acyclovir prophylaxis is not routinely recommended for pregnant women with recurrent genital herpes 5
Foscarnet use in pregnancy should be reserved for life-threatening maternal HSV infection when acyclovir resistance is documented 1, 2

The Centers for Disease Control and Prevention suggests that suppressive acyclovir therapy in immunocompetent patients has not been associated with emergence of clinically significant resistance even after 6 years of daily use 6
After 1 year of suppressive therapy, reassess the need for continuation as recurrence frequency decreases over time 6