High prevalence but low clinical impact of acyclovir-resistant herpes simplex virus type 1 infections in patients with hematologic disorders.

Background/purpose: Herpes simplex virus type 1 (HSV-1) is highly prevalent in immunocompromised patients. Due to the recurrent nature of HSV-1 infection, frequent exposure to antiviral agents raises concerns about drug resistance. This study aimed to investigate antiviral-resistant profiles of HSV-1 and discuss the clinical impact of acyclovir-resistant (ACV-R) compared to acyclovir-susceptible (ACV-S) HSV-1 infected patients.

Methods: Repeated sampling specimens during 2010-2023 from all age groups were collected and only those with clinical correlations were illegible to be assessed. Plaque reduction assay and Sanger sequencing were used to determine phenotypic and genotypic profiles (UL23/UL30 genes) of ACV-R HSV-1 isolates, respectively.

Results: A total of 29 HSV-1 isolates from 18 patients, mainly with hematologic disorders (n = 14, 77.8 %) and the clinical diagnosis of orolabial diseases (n = 14, 77.8 %), were analyzed. The prevalence of ACV-R HSV-1 isolates was 69.0 % (20/29). Most isolates were exposed to antiviral agents before sampling (21/29, 72.4 %). There was no statistical difference in treatment response and duration between patients infected with ACV-S and ACV-R isolates (p = 0.274). No strong correlation could be observed between point mutations, 50 % effective concentration value, and previous antiviral exposure duration. Novel mutations E676K and P355S were detected and probably associated with ACV resistance.

Conclusions: The prevalence of ACV-R HSV-1 was higher than reported data from the literature. Several novel mutations were discovered and could enrich the ACV-R HSV-1 database. Further studies are needed to investigate ACV resistance in other potentially related genes, such as UL5 and UL42.