Periodontitis is an inflammatory pathology that destroys periodontitis and causes tooth loosening. Its high incidence, combined with very high oral and systemic morbidity, places this pathology at the heart of global public health priorities. The current therapeutic management of periodontitis is not satisfactory because it often leads to a stabilization of the disease, marked by frequent recurrences, especially severe forms. Improving the treatment of patients with periodontitis is therefore an essential priority.

If gingival bacterial dysbiosis is a major contributing factor, this model has clinical-biological limitations that suggest that other etiological factors are involved, and worsen the pathology. In particular, the literature provides clear evidence that periodontal lesions are mostly infected with Herpes EBV, CMV and HSV-1 viruses and that periodontal infection with these viruses is very directly correlated with disease progression (severity). In addition, our work provides new cellular and molecular data that demonstrate mechanisms of active EBV infection of cells and periodontal structures, and highlight inflammatory and necrotic effects associated with this infection. Given these observations and the high pathogenicity of herpes viruses, all known to be powerful inflammatory, lytic and immunomodulatory agents, it seems difficult not to evoke a direct etiopathogenic role of these viruses capable of acting synergistically with periodontopathogenic bacteria.

In this context, the use of an antiviral appears as a very attractive therapeutic proposal to effectively treat periodontitis in combination with conventional treatments. This original and innovative proposal can also be easily and quickly validated in a randomized therapeutic trial through the availability of antiviral molecules that are non-toxic and very specific to human herpes viruses that are derivatives of aciclovir.

Inclusion criteria:

• Age ≥ 18
• Diagnosis of periodontitis induced by bacterial biofilms of dental plaque, generalized, stage III or IV and grade A, B or C
• Patients of childbearing age will need to use an effective method of contraception for the duration of their study participation
• Signature of informed consent
• Membership of a social security scheme

Exclusion criteria:

• Necrotizing periodontitis
• Pathologies requiring prophylactic antibiotics therapy (which may influence treatment)
• Non-surgical periodontal treatment completed within 6 months prior to inclusion
• Patients with enhanced protection, namely lactating women, persons deprived of liberty by judicial or administrative decision, person over 18 under legal protection
• Patients who do not accept conventional therapy (gingival debridement not covered by the social security system (performed in each center)
• Periodontitis as a direct manifestation of systemic diseases
• Major systemic pathologies (diabetes, HIV, cancers, immunocompromised patients)
• Negative serology for EBV: a blood test will be performed. the results will be communicated to the patient by the dental surgeon
• Pregnant woman: a blood pregnancy test will be carried out for women of childbearing age who do not have contraception. Results will be communicated to the patient by the dental surgeon
• Renal failure (creatinine clearance < 60 mL/min)
• Systemic antibiotic therapy or any medication affecting the periodontal environment (systemic antibiotics, antiepileptics, immunosuppressants, calcium inhibitors) taken within 6 months of inclusion
• Nephrotoxic medications (aminoglycosides, organoplatinums, iodized contrast agents, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus)
• Hypersensitivity to valaciclovir, aciclovir or one of the excipients
• History of DRESS syndrome under valaciclovir treatment.