Refractory Mucocutaneous Infections by Herpes Simplex Virus (HSV) in Hematopoietic Cell Transplant Recipients: A Real-world, Multicenter Study

Background: We examined treatment patterns and clinical outcomes of adult hematopoietic cell transplant (HCT) recipients with refractory mucocutaneous herpes simplex virus (HSV) infection from 7 US centers. Methods: Multicenter, retrospective study of laboratory confirmed HSV infection and failure to improve after ≥7 days of appropriately dosed anti-HSV therapies. Resistance testing was performed at clinicians' discretion. Therapies were captured for the first refractory HSV infection post-HCT (index episode). Time to complete lesion healing, toxicities, and HSV recurrence up to 1 year from index HSV episode lesion healing were extracted from electronic medical records. The cumulative incidence function was used to estimate time to healing with death as competing risk. Results: Of 125 patients, acyclovir resistance was confirmed in 85/104 patients (81.7%) tested. First therapy was nucleoside analog in 100 patients and foscarnet in 25. A total of 110 patients (88%) received second line therapy(ies), including foscarnet (94), intravenous cidofovir (6), and/or topical antivirals (21). Mean treatment durations (SD) were 21.8 days (13.8), 20.3 (10.1), and 41.0 (37.5) for foscarnet, cidofovir, and topicals, respectively. Complete healing occurred in 69 patients (55.2%) at a median of 38 days (range 257) from the anti-HSV therapy start. Nephrotoxicity was reported during 40.4% of foscarnet and 50.0% of cidofovir courses, respectively. Among 69 patients with completed healing, 27 (39.1%) experienced HSV recurrence during follow up. Conclusions: Our study highlights the challenges of managing refractory HSV post-HCT during the study timeframe, and underscores the unmet need for safer, more effective, and orally bioavailable therapies for refractory HSV.