Can (or have) antiviral drugs created drug-resistant viruses?

Question

Evolution/emergence of antibiotic-resistance in bacteria is a known effect of extensive use of pharmaceutical antibiotics.

Pharmaceutical antivirals have come into extensive use in recent decades – e.g., Tamiflu for influenza; Harvoni for hepatitis C; Valtrex for herpes. Some are even prescribed as ongoing "suppressants."

Has anything analogous to antibiotic resistance (i.e., antiviral resistance) been observed in viruses treated with pharmaceutical antivirals? If not, are there theoretical reasons this would be unlikely (or impossible) to occur?

Answer 1

Resistance to antiviral therapy is a problem in the treatment of many viral illnesses.

Influenza is particularly significant given the epidemiological characteristics of the disease. This Nature Medicine article gives a good overview of oseltamivir resistant pandemic H1N1, which is a useful example, since our assumption that resistant virus would not spread very effectively was (probably predictably) not valid.

HIV is an excellent case study as well, since antiretroviral resistance is such an important issue in the treatment of that particular infection, and demonstrates the challenges of outwitting a pathogen with such a high error rate. This became apparent quite soon after introduction of (initially successful) monotherapy with AZT. In fact, preventing the emergence of resistant virus within the population of virus in a given patient is typically the primary consideration in choosing a drug regimen.

With regard to the other examples of antiviral treatment you mentioned, HCV resistance is well reviewed here. HSV resistance is reviewed here. Resistance has been observed in both examples, though it is more often considered in the normal course of treatment for HCV than HSV. I'd note that Harvoni, which you mentioned, is a combination therapy (ledipasvir-sofosbuvir). Combination therapy is one common strategy for preventing the emergence of resistance