Acyclovir is an antiviral drug that is commonly used to treat infections caused by herpes simplex virus (HSV) and varicella-zoster virus (VZV). However, the development of resistance to acyclovir has become a growing concern in recent years.

According to a study published in the Journal of Antimicrobial Chemotherapy [3], acyclovir resistance can develop due to a number of factors. One of the main causes is the mutation of the viral thymidine kinase (TK) gene, which is responsible for activating acyclovir within the infected cells. Mutations in the TK gene can reduce the ability of the virus to activate acyclovir, leading to drug resistance.

Another factor that can contribute to acyclovir resistance is the overexpression of the viral TK gene. This can occur due to gene amplification or other mechanisms, leading to increased levels of TK protein and decreased sensitivity to acyclovir.

Additionally, the study found that prolonged use of acyclovir can also contribute to the development of resistance. This is because the drug can select for resistant strains of the virus, which can then become dominant in the population.

It is important to note that acyclovir resistance is still relatively uncommon, and most patients respond well to treatment with the drug. However, in cases where resistance does develop, alternative treatment options may need to be considered.

In conclusion, acyclovir resistance can develop due to mutations in the viral TK gene, overexpression of the TK gene, and prolonged use of the drug. While resistance is still relatively rare, it is important for healthcare providers to monitor patients for signs of resistance and consider alternative treatment options if necessary.

Sources:
[1] https://www.drugpatentwatch.com/p/tradename/ACYCLOVIR
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871161/
[3] https://pubmed.ncbi.nlm.nih.gov/8548189/