Refractory Mucocutaneous Infections by Herpes Simplex Virus (HSV) in Hematopoietic Cell Transplant Recipients: A...

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.

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.

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.

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.