Topical Treatment of Acyclovir-Resistant Herpes Simplex Virus Stomatitis after Allogeneic Hematopoietic Cell Transplantation

Abstract

<b><i>Introduction:</i></b> We report on patients who developed severe acyclovir-resistant (ACVr) herpes simplex virus 1 (HSV-1) stomatitis after allogeneic hematopoietic cell transplantation (HCT). <b><i>Patients:</i></b> HCT patients suffering from HSV-1 stomatitis without response after 1 week of high-dose acyclovir (ACV) were tested for ACV resistance. Patients with proven ACV resistance were treated either topically with cidofovir solution and gel or with topical foscavir cream or with intravenous foscavir. <b><i>Results:</i></b> Among 214 consecutive HCT patients, 6 developed severe ACVr HSV-1 stomatitis (WHO grade III <i>n</i> = 1, WHO grade IV <i>n</i> = 5). All 6 patients suffered from relapse of acute myeloid leukemia (AML) after HCT. ACVr stomatitis was treated topically with first-line (<i>n</i> = 4) or second-line (<i>n</i> = 2) cidofovir. Topical foscavir cream was applied as first-line (<i>n</i> = 1) or second-line (<i>n</i> = 1) therapy. Intravenous foscavir was used in 3 patients (first-line therapy, <i>n</i> = 1; second-line therapy, <i>n</i> = 2). Complete remission was reached by topical cidofovir (<i>n</i> = 3), topical foscavir (<i>n</i> = 1), and intravenous foscavir (<i>n</i> = 1), respectively. Five of the 6 patients died due to progression of leukemia. Only 1 patient survived. <b><i>Conclusions:</i></b> ACVr HSV-1 stomatitis is a severe complication in AML patients relapsing after HCT. It reflects the seriously impaired general condition of these patients. This analysis shows that topical treatment with cidofovir or foscavir might be a sufficient first-line therapy approach in ACVr HSV-1 stomatitis. It might serve as a less toxic alternative to intravenous foscavir.

Management of oral herpes simplex virus infections: The problem of resistance. A narrative review

“…Studies in HIV positive individuals and HSCT recipients, including isolated cases reports as well as randomized phase II trials, show that intravenous administration of FOS is effective in treating severe ACVr HSV-1 and -2 mucocutaneous lesions, since it reduces viral shedding along with the size and duration of lesions (Chatis et al, 1989;Iino et al, 1996;MacPhail et al, 1989;Naik et al, 1995;Sall et al, 1989;Verdonck et al, 1993), being more efficacious and showing less toxicity compared to vidarabine (Safrin et al, 1991). A few reports have also shown good results using FOS cream 1%-2.4% for the treatment of orogenital and cutaneous ACVr HSV lesions (Heidenreich et al, 2020;Javaly et al, 1999;Pechère et al, 1998; Table 1).…”

“…CDV has been used efficiently for the systematic treatment of HSV‐1 and ‐2 mucocutaneous infections with resistance to ACV and/or FOS in HSCT recipients (Blot et al, 2000; Bryant et al, 2001). Although it is available only as an IV formulation due to its low oral bioavailability, topical use of 1%, 3% and 5% CDV gel or 3% oral rinse in various frequencies and durations has shown satisfactory results in patients with AIDS and HSCT recipients (Epstein et al, 2016; Evans et al, 2011; Heidenreich et al, 2020; Lalezari et al, 1994; Lateef et al, 1998; Muluneh et al, 2013; Sims et al, 2007; Snoeck et al, 1993). Interestingly, in one case intralesional injection resulted in significant improvement of a nasal ACVr HSV infection (Castelo‐Soccio et al, 2010; Table 2).…”

Herpes Simplex Virus and Varicella Zoster Virus Infections in Cancer Patients

“…A dosing of 40–60 mg/kg every 8 h intravenously is commonly used in such settings. Topical foscarnet has also been used for treatment of mucocutaneous acyclovir-resistant HSV infections [ 67 ].…”

Resistant herpes simplex virus infections – who, when, and what's new?

“…For localized lesions, topical cidofovir (1% cream) and foscarnet (2% cream) have been used successfully [10 ▪ ], with minimal systemic absorption observed. Although not available commercially, topical cidofovir or foscarnet can be compounded for use twice a day until the lesion(s) resolves.…”