Acyclovir is an antiviral medication that is commonly used to treat herpes simplex virus (HSV) infections. The drug works by inhibiting the viral DNA polymerase, which is necessary for the virus to replicate. While acyclovir is generally considered to be a safe and effective treatment, there is concern that prolonged use of the drug could lead to the development of resistance.

According to DrugPatentWatch [1], acyclovir was first approved by the FDA in 1985 and is currently available as a generic drug. The patent for the original brand-name version of acyclovir expired in 1997, which has led to the availability of several generic versions of the drug.

A study published in the Journal of Clinical Virology [3] suggests that resistance to acyclovir can develop in patients who are immunocompromised or who have prolonged exposure to the drug. The study found that patients who had received acyclovir for more than 12 months were more likely to develop resistance to the drug than those who had received the drug for shorter periods of time. The study also found that patients who were immunocompromised were more likely to develop resistance to acyclovir than those who were not.

Another study published in the Journal of Infectious Diseases [2] found that acyclovir-resistant strains of HSV can emerge in patients who have frequent recurrences of genital herpes. The study found that these resistant strains were more likely to develop in patients who had received long-term suppressive therapy with acyclovir.

In conclusion, while acyclovir is generally considered to be a safe and effective treatment for HSV infections, there is concern that prolonged use of the drug could lead to the development of resistance. Patients who are immunocompromised or who have frequent recurrences of genital herpes may be at a higher risk of developing resistance to acyclovir. Healthcare providers should monitor patients who are receiving long-term therapy with acyclovir for signs of resistance and consider alternative treatment options if resistance is suspected.

Sources:
[1] https://www.drugpatentwatch.com/p/tradename/ACYCLOVIR
[2] https://pubmed.ncbi.nlm.nih.gov/8548189/
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC145299/