Tecovirimat resistance in a person with advanced HIV and delayed ART
Simon Collins, HIV i-Base
Although tecovirimat is currently being used to treat mpox it has a low genetic barrier to drug resistance. The Annals of Internal Medicine published a very difficult case report of a 53-year-old man diagnosed with advanced HIV and who on autopsy also showed tecovirimat-resistant mpox.
He presented in November 2022 with symptoms of advanced HIV infection including weight loss, a longstanding large, painful anal ulcer; and proctitis, but without skin lesions. His CD4 and viral load were 20 cells/mm3 and 523,000 copies/mL respectively. He also had chronic HBV, latent syphilis, Cryptococcus neoformans antigenemia, anal Chlamydia trachomatis infection, and suspected CMV colitis.
However, he did not start ART for a further six weeks after worsening anal pain and lesions that were mpox positive. Treatments for HIV (Biktarvy), CMV (IV ganciclovir) and mpox (tecovirimat) were all started.
Tecovirimat was given 600 mg twice-daily and the majority of lesions resolved within two weeks. However, some anal lesions and viral shedding persisted, and further testing was run. Retrospective sequence analysis identified a F13L mutation, present from day 11, which confers tecovirimat resistance.
Although mpox DNA was no longer detectable in blood after day 25, it remained high up to day 48 (Ct, 21.58) and detectable up to the end of follow-up (Ct, 33.94 at day 88).
However, the retrospective analysis also showed protracted mpox shedding for at least 87 days before the use of tecovirimat, when a minor fraction of the resistant variant was already detectable.
This case highlights the rapid development of tecovirimat resistance in the context of multiple clinical complications and advanced HIV, despite recovery of CD4 count to approximately 100 cells/mm3 by day 48.
Mertes H et al. Tecovirimat resistance in an immunocompromised patient with Mpox and prolonged viral shedding. Annals of Internal Medicine. DOI:10.7326/L23-0131. (25 July 2023).