Efficacy of anti-microbial photodynamic therapy in managing herpes simplex virus: A systematic review of clinical studies

BACKGROUND: Herpes simplex virus (HSV) infections are a common clinical concern, often requiring effective antiviral treatments. Anti-microbial photodynamic therapy (aPDT) has gained attention as a potential adjunct to conventional therapies for managing HSV outbreaks. This systematic review aimed to evaluate the efficacy of aPDT in treating HSV infections. METHODS: Following PRISMA guidelines, PubMed/MEDLINE, Scopus, Embase, and Web of Science online databases were systematically searched for relevant studies on July 2025. Healing time was considered as the primary outcome, and secondary outcomes included lesion size, viral load, and patient-reported outcomes. Clinical studies evaluating efficacy of aPDT against other therapeutic approaches with at least 10 patients were considered eligible. Quality appraisal of the included studies was conducted using the revised Cochrane risk-of-bias tool for randomized trials (RoB2) and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I). In addition, the certainty of evidence was assessed with a modified version of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework adapted for reviews without quantitative synthesis. RESULTS: aPDT monotherapy demonstrated clinical outcomes comparable to conventional antiviral therapy, with reductions in viral load and edema but limited superiority in clinical healing parameters. In contrast, adjunctive use of aPDT with antiviral therapy consistently improved pain, inflammatory markers, viral load, healing outcomes, and recurrence rates compared with either treatment alone. CONCLUSION: aPDT appears to be an effective adjunctive therapy for HSV infections, but further high-quality studies are necessary to refine treatment protocols and confirm its clinical benefits.