How We Diagnose and Manage Refractory and Resistant Herpes Simplex Virus Mucocutaneous Infection After Hematopoietic Cell Transplantation.

Abstract

Background: Herpes simplex virus (HSV) infection is a clinically significant complication in hematopoietic cell transplant (HCT) recipients. Refractory and resistant (R/R) HSV infections may occur in this patient population, particularly after prolonged exposure to anti-HSV agents.

Objectives: To provide a comprehensive review of the diagnostic approach and the treatment options for R/R HSV mucocutaneous infections in HCT recipients and to highlight future treatment strategies.

Sources: We searched the PubMed Central Database and Embase to identify published studies on R/R HSV infections in HCT recipients. We used the search terms "herpes simplex virus," "resistant*," OR "refractory," "immunocompromised," "immunosuppress*," and "immunodeficien*," and screened the results for articles reporting R/R HSV infections among HCT recipients. We chose an HCT recipient with a complicated refractory HSV infection as a representative clinical case.

Content: A clear clinical definition of refractory HSV infection is currently not available, which can lead to delays in diagnosis and treatment, negatively impacting patient care. Apart from two small randomized controlled trials in the 1990s that looked at treatment with systemic foscarnet and topical cidofovir in patients living with human immunodeficiency virus, all treatment recommendations for R/R HSV infections are based on observational studies and case reports. The use of alternative treatment options often comes with serious side effects, such as kidney toxicity. This underscores the urgent need for safer and effective treatment options. Pritelivir, a new oral antiviral medication, is currently being studied in a phase 3 trial for R/R HSV infections in immunocompromised patients. Limited data from the Early Access Program, which allows compassionate use, suggests that pritelivir holds promise as a treatment option for HCT recipients with R/R HSV infections.

Implications: The proposed R/R HSV mucocutaneous infection diagnostic and treatment algorithm guides the appropriate management of these difficult-to-treat infections, potentially improving patient outcomes.