Tecovirimat resistance in an immunocompromised patient with mpox and prolonged viral shedding

Background: Tecovirimat, an inhibitor of the viral VP37 envelope-wrapping protein used to treat severe monkeypox virus (MPXV) infection, has a low barrier to resistance (1, 2). A tecovirimat-resistant MPXV variant was recently identified at the autopsy of an immunocompromised patient with mpox after prolonged tecovirimat treatment (3).

Objective: To describe the rapid selection of a tecovirimat-resistant MPXV variant during treatment of a severely immunocompromised patient with prolonged MPXV infection.

Case Report: A 53-year-old man who had been vaccinated for smallpox in childhood presented in November 2022 with weight loss; a longstanding large, painful anal ulcer; and proctitis, but without skin lesions. Work-up revealed HIV-1 infection with pronounced immunosuppression (plasma viral load, 523 000 copies/mL; CD4+ T-lymphocyte count, 0.02 × 109 cells/L), chronic hepatitis B virus infection, latent syphilis, Cryptococcus neoformans antigenemia, anal Chlamydia trachomatis infection, and cytomegalovirus infection.