When viruses become less susceptible to antiviral drugs due to genetic changes【682704506262144†L138-L158】
Explanation
Antiviral resistance arises when a virus evolves to evade the effects of drugs designed to inhibit it. Antiviral medicines target specific viral proteins or steps in replication, such as neuraminidase in influenza, reverse transcriptase in HIV or polymerase in hepatitis viruses. During replication, viruses, especially RNA viruses, mutate frequently; selection pressure from drug exposure can favour variants with alterations in the drug’s target or increased expression of efflux mechanisms. These changes reduce binding of the drug or prevent activation, allowing the virus to replicate despite therapy. Resistance can emerge during or after treatment, or less commonly arise spontaneously in untreated infections【682704506262144†L138-L158】. Factors that accelerate antiviral resistance include prolonged treatment, suboptimal dosing, poor adherence and the use of monotherapy when combination therapy is recommended.
Mechanisms and examples
In influenza viruses, mutations in the neuraminidase gene, such as the H275Y substitution in A(H1N1)pdm09 strains, confer reduced susceptibility to oseltamivir and other neuraminidase inhibitors. Changes in the viral M2 ion channel led to widespread resistance to the adamantane class, prompting cessation of their use【682704506262144†L160-L173】. For HIV, single amino acid substitutions in reverse transcriptase or protease can markedly decrease binding of nucleoside and non‑nucleoside inhibitors; therefore, antiretroviral therapy combines three or more drugs with different targets to suppress replication and limit resistance. Herpes simplex virus may develop thymidine kinase or DNA polymerase mutations that confer acyclovir resistance, particularly in immunocompromised patients. Hepatitis B virus variants resistant to lamivudine and other nucleoside analogues arise through polymerase mutations. Laboratory surveillance uses phenotypic assays and genomic sequencing to detect reduced susceptibility, and resistant strains are tracked to inform treatment guidelines【682704506262144†L138-L158】.
Antiviral resistance threatens the efficacy of current therapies, highlighting the need for combination regimens, careful dosing, adherence and ongoing surveillance.
Related Terms: Antimicrobial Resistance, Antivirals, Mutation, Antiretroviral, Antibacterial