Studies reveal resistance to tecovirimat in mpox patients with weak immune systems

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Ninety-six isolates from 46 US mpox patients were resistant to the antiviral drug tecovirimat (Tpoxx), although most were from patients with severely weakened immune systems who took multiple courses of the drug, according to a study published yesterday in Emerging Infectious Diseases.

A Centers for Disease Control and Prevention (CDC) research team tested 124 isolates from 68 patients for tecovirimat resistance during the global mpox outbreak that began in May 2022.

"The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat," the authors wrote. "Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations."

Most resistant isolates were from patients with very weak immune systems who took multiple courses of the drug, while most isolates found through routine surveillance of patients who didn't receive tecovirimat were sensitive to the drug.

"The frequency of resistant viruses remains relatively low (<1%) compared with the total number of patients treated with tecovirimat," the researchers wrote.

Need to consider antiviral resistance

In the same journal, a Stanford University-led team published a case report of successful treatment of an HIV/AIDS patient diagnosed as having mpox with suspected tecovirimat resistance. The 35-year-old California man sought care because of diffuse skin lesions and was given a 2-week course of tecovirimat.

His lesions worsened, and he returned 8 weeks later with ulcerated lesions on his nose, finger, feet, anogenital regions, and abdomen. Antiviral medications, including tecovirimat, were given, but 1 month later, his lesions had worsened, and new lesions were emerging. Repeat testing of a chin lesion confirmed the persistence of mpox infection with a high viral load.

Clinicians caring for patients who have persistent mpox should evaluate for underlying immunodeficiency.

Tecovirimat was continued, and intravenous and topical preparations of the antiviral drug cidofovir were given. Within days, the lesions began resolving, and whole-genome sequencing revealed resistance-associated mutations.

"Clinicians caring for patients who have persistent mpox should evaluate for underlying immunodeficiency, particularly HIV, and consider the possibility of antiviral resistance in cases that fail to respond to standard of care," the authors wrote. 

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