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BACKGROUND The recent mpox outbreak has disproportionately affected people with HIV (PWH) and resulted in the first widespread use of the novel antiviral tecovirimat. Whether treatment outcomes differ between PWH and those without HIV is unknown. OBJECTIVE To compare the clinical presentation and treatment outcomes of PWH and HIV-negative persons with mpox virus (MPXV) infection treated with tecovirimat. DESIGN Retrospective cohort study of patients treated with tecovirimat for confirmed MPXV infection from June to August 2022. SETTING Two academic medical centers in New York City. PARTICIPANTS The study included 196 persons treated with tecovirimat from 20 June to 29 August 2022. Of 154 testing positive for MPXV, 72 were PWH and 4 had a CD4 count lower than 0.20 × 109 cells/L. MEASUREMENTS Patient demographic characteristics, clinical presentation, treatment outcomes, and safety data for tecovirimat. RESULTS Indications for tecovirimat treatment were similar between the PWH and HIV-negative groups. Four participants had serious adverse events; none were attributed to tecovirimat. Three of these 4 participants had HIV infection, and 2 had CD4 counts less than 0.20 × 109 cells/L. Twenty-two percent of participants had nonsevere adverse effects. Groups had similar rates of hospitalization, indications for treatment, and co-occurring infections, but PWH had fewer days from symptom onset to treatment (7.5 vs. 10). There was no difference in treatment outcomes, including days to improvement or rate of persistent symptoms. LIMITATION Patients with mpox who were not treated with tecovirimat were not followed routinely and therefore lacked comparable outcome data, limiting evaluation of efficacy. CONCLUSION In our cohort of patients treated with tecovirimat for severe mpox, HIV status did not seem to affect treatment outcomes. PRIMARY FUNDING SOURCE National Institutes of Health.