Researchers describe case of tecovirimat-resistant mpox variant in patient with prolonged infection

Abstract: https://www.acpjournals.org/doi/10.7326/L23-0131

Authors from the Institute of Tropical Medicine, Nationalestraat, Antwerp, Belgium describe a case of tecovirimat-resistant mpox virus (MPXV) identified at the autopsy of a severely immunocompromised patient with prolonged disease. Tecovirimat, an antiviral used to treat severe mpox virus, has a low barrier to resistance, which makes this case particularly unusual. The case report is published in Annals of Internal Medicine.

A 53-year-old patient presented with severe symptoms of MPXV that had been present for several weeks. The patient had several co-infections including active HIV infection, chronic hepatitis B virus infection, latent syphilis, and anal Chlamydia. Oral tecovirimat was started 1 day after the confirmation of MPXV and the initial 2-week course was successful. However, the anorectal viral load remained high up to day 48 and detectable up to the end of follow-up. Retrospective MPXV sequencing of the anorectal samples revealed a dominant variant population. This mutation was associated with a 350-fold increase in the half maximal effective concentration of tecovirimat compared with typical virus.

According to the authors, this case confirms the potential rapid selection of resistant mutant virus during tecovirimat monotherapy and could be the first to study this phenomenon longitudinally. The rapid selection of resistance in this patient highlights the risk of tecovirimat monotherapy, especially in the context of prolonged disease and immunosuppression. In such cases, the authors advocate for surveillance for resistant variants, emphasis on immune reconstitution, monitoring of viral clearance, and strict adherence to infection prevention measures.

Media contacts: For an embargoed PDF, please contact Addison Dunlap at [email protected]. To speak with the corresponding author, Koen Vercauteren, please email [email protected].