Orolabial and Genital Herpes Clinical Trials: A Meta-analysis of Endpoints

Although several antiviral agents are licensed for the treatment of orolabial and genital herpes simplex virus infections, new therapies are needed. Trial design is challenging for these indications due to the heterogeneity of endpoints in prior trials. We conducted a systematic review and meta-analysis of randomized placebo-controlled trials published between 1995 and 2024 consisting of adults with established herpes simplex virus infection who were immunocompetent and nonpregnant. A total of 22 articles met the inclusion criteria. For episodic treatment, endpoints included time to healing, proportion with an aborted lesion, and time to cessation of symptoms. For daily suppressive therapy, endpoints included time to first recurrence, proportion recurrence-free at 1 year, and total shedding rate. We observed that over the last 30 years, clinical trials have used various endpoints with nonstandardized definitions. A reassessment of appropriate endpoints along with regulatory guidance would assist with consistent study design for evaluation of new agents.