DESIGN: Systematic literature review.

DATA SOURCES: Seven databases were searched from inception to 31 August 2020. A focused search was performed to supplement the results.

ELIGIBILITY CRITERIA: Studies which reported either healthcare resource utilisation or costs associated with HSV-related healthcare, including screening, diagnosis and treatment of genital HSV infection and neonatal herpes prevention and treatment.

DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the risk of bias using the Larg and Moss's checklist. All data were summarised narratively.

RESULTS: Out of 11 443 articles, 38 were included. Most studies (35/38, 94.6%) were conducted in high-income countries, primarily the United States, and were more often related to the prevention or management of neonatal herpes (n=21) than HSV genital ulcer disease (n=17). Most analyses were conducted before 2010. There was substantial heterogeneity in the reporting of HSV-related healthcare resource utilisation, with 74%-93% individuals who sought care for HSV, 11.6%-68.4% individuals who received care, while neonates with herpes required a median of 6-34 hospitalisation days. The costs reported were similarly heterogeneous, with wide variation in methodology, assumptions and outcome measures between studies. Cost for screening ranged from US$7-100, treatment ranged from US$0.53-35 for an episodic therapy, US$240-2580 yearly for suppressive therapy, while hospitalisation for neonatal care ranged from US$5321-32 683.