Antiviral Resistance in the Genomic Era: Molecular Mechanisms, Clinical Challenges, and Pharmacogenetic Perspectives

Antiviral treatment (ART) resistance is an emerging global phenomenon that reduces the effectiveness of antiviral therapies and raises strong challenges for public health systems. This literature review focuses on the factors that contribute to developing antiviral drug resistance and the scope of pharmacogenetics. Studies have shown that inefficient use of antiviral therapies, genetic mutations in virus strains, and a limited healthcare framework are the main factors that increase resistance rates. Specifically, the poor adherence in HIV patients, combined with the virus high mutation, are the primary driver of drug-resistant strains development. The mutations in NS5A region reduce the efficacy of HCV direct-acting antivirals (DAAs). Where Influenza virus resistance to neuraminidase inhibitors (NAIs) like oseltamivir has been identified in seasonal strains, most notably the H275Y mutation in H1N1. Consequently, development of these resistant strains demands multidisciplinary strategies, global coordination, effective resistance monitoring systems, and public health initiatives to overcome this phenomenon. The paper aims to present a full picture of the antiviral drug resistance, which may provide better insights for clinicians and researchers.