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EPIC-HR evaluated the oral antiviral nirmatrelvir/ritonavir in symptomatic, unvaccinated, high-risk adults with nonhospitalized COVID-19. Early treatment substantially reduced progression to hospitalization or death compared with placebo. The clinical importance extends beyond the original trial population because it established a model of early outpatient antiviral therapy for people at high risk of severe disease. For internists, timing is crucial: treatment must begin soon after symptom onset and eligibility should be assessed rapidly. Ritonavir causes major drug-drug interactions through CYP3A inhibition, so a careful medication review is mandatory. Renal function also affects dosing. The study highlights a broader principle in infectious diseases: when the therapeutic window is narrow, systems that enable rapid diagnosis, risk stratification and prescribing can be as important as the drug itself. In current practice, treatment decisions must be aligned with the circulating variant landscape and up-to-date national guidance.
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EPIC-HR evaluated the oral antiviral nirmatrelvir/ritonavir in symptomatic, unvaccinated, high-risk adults with nonhospitalized COVID-19. Early treatment substantially reduced progression to hospitalization or death compared with placebo. The clinical importance extends beyond the original trial population because it established a model of early outpatient antiviral therapy for people at high risk of severe disease. For internists, timing is crucial: treatment must begin soon after symptom onset and eligibility should be assessed rapidly. Ritonavir causes major drug-drug interactions through CYP3A inhibition, so a careful medication review is mandatory. Renal function also affects dosing. The study highlights a broader principle in infectious diseases: when the therapeutic window is narrow, systems that enable rapid diagnosis, risk stratification and prescribing can be as important as the drug itself. In current practice, treatment decisions must be aligned with the circulating variant landscape and up-to-date national guidance.
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