Abstract Background Cytomegalovirus (CMV) reactivation is increasingly recognized as a contributor to disease exacerbation in ulcerative colitis (UC). This study is aimed to evaluate the effect of antiviral therapy on CMV DNA titre and immunohistochemical (IHC) staining in CMV-positive UC patients. Methods In this prospective cohort study, 47 CMV-positive UC patients were enrolled between June 2023 and March 2025. Patients were stratified into two groups: Cohort A (n = 31), who received antiviral therapy (ganciclovir) in addition to standard medical therapy for UC, and Cohort B (n = 16), who received standard medical therapy alone. Clinical parameters, laboratory indices, CMV DNA titre, and IHC marker were compared between two groups after 21 days. Results By day 21, Cohort A showed significant reductions: IHC scores declined from 2.0 (0–10) to 0.0 (0–4) (P = 0.001), CMV DNA decreased from 69,147 (186–4,035,903) to 129 (0–6,933,397) copies/mL (P = 0.001). In Cohort B CMV DNA rose from 3,487 (21–213,440) to 11,888 (0–401,753) copies/mL (P = 0.940). Among those positive, complete IHC clearance & complete DNA clearance occurred in 54.8% vs 12.5% & 41.9% vs 25.0% (Cohort A vs Cohort B) respectively. Conclusion Antiviral therapy in CMV-positive UC patients resulted in significant reductions in mucosal CMV DNA titre and IHC expression. Despite antiviral benefit, complete viral clearance was not achieved in all patients, indicating that CMV persistence is multifactorial and may require adjunctive therapeutic strategies beyond antivirals alone. Conflict of interest: Bansal, Maadhav Gopal: No conflict of interest Yadav, Dawesh Prakash: No conflict of interest Yadav, Mahima: No conflict of interest Tiwari, Anurag: No conflict of interest Kumar, Vinod: No conflict of interest Shukla, Sunit Kumar: No conflict of interest Singh, Pranjal: No conflict of interest Gupta, Anand Kumar: No conflict of interest Mishra, Shyamalendu Bikash: No conflict of interest Bassi, Nitesh: No conflict of interest
Bansal et al. (2026) studied this question.