Herpes simplex virus resistance to acyclovir: clinical relevance

Area of Science:

• Virology
• Pharmacology
• Infectious Diseases

Background:

• Herpes simplex virus (HSV) infections are common and typically treated with acyclovir.
• Acyclovir is activated intracellularly by viral thymidine kinase and host kinases, inhibiting viral DNA polymerase.
• Resistance to acyclovir is emerging due to mutations in viral thymidine kinase or DNA polymerase genes.

Purpose of the Study:

• To review the incidence and mechanisms of acyclovir resistance in HSV.
• To highlight the clinical implications of drug-resistant HSV, especially in immunocompromised patients.
• To emphasize the need for ongoing surveillance of acyclovir-resistant HSV.

Main Methods:

• Review of existing surveys and case reports on acyclovir resistance in HSV.
• Analysis of mutation types leading to resistance (thymidine kinase deficiency or polymerase alterations).
• Comparison of resistance prevalence in immunocompetent versus immunocompromised populations.

Main Results:

• Thymidine kinase deficiency accounts for approximately 95% of acyclovir-resistant HSV isolates.
• Acyclovir resistance remains stable at ~3% in immunocompetent hosts but is increasing in immunocompromised patients.
• Clinical disease from resistant HSV is primarily seen in immunocompromised individuals, often presenting as chronic ulcerative lesions.

Conclusions:

• Acyclovir resistance in HSV is a growing concern, particularly in immunocompromised populations like those with AIDS or post-bone marrow transplant.
• While person-to-person transmission of resistant strains is not documented, increased antiviral use raises this possibility.
• Continuous monitoring for acyclovir-resistant HSV is essential in both immunocompetent and immunocompromised individuals.