Prevention of Recurrence of Herpes Simplex in Autoimmune Rheumatic Diseases

HSV-1 and HSV-2 are ubiquitous human pathogens that can establish lifelong latency, with the potential for frequent reactivation. Immunocompromised individuals, including patients with ARDs, are particularly vulnerable to more severe and disseminated HSV infections, which may result in significant morbidity and even mortality. Despite this, the true incidence and burden of HSV reactivation in ARD patients under immunosuppression remain underexplored. Previous studies in solid-organ transplant recipients and people living with HIV have demonstrated that prophylactic or suppressive antiviral therapy with acyclovir can significantly reduce HSV-related complications. However, no randomized controlled trials to date have evaluated the efficacy and safety of this approach in ARD patients under frequent immunosuppressive drug use and recurrent HSV in this group. This trial will enroll 62 participants with ARDs and prior recurrent HSV infection, randomly assigned to receive oral acyclovir or placebo for 12 months, followed by continued monitoring for an additional year. Primary outcomes include the number of clinically confirmed HSV reactivations in acyclovir and placebo groups. Secondary outcomes include safety (adverse events), treatment tolerability, and identification of clinical and therapeutic risk factors for HSV recurrence. By providing high-quality evidence through a rigorously controlled methodology, this study seeks to fill a critical knowledge gap in rheumatology, offering practical guidance for antiviral prophylaxis in immunosuppressed ARD patients, ultimately improving patient safety and clinical outcomes in a vulnerable population.