From the FDA Drug Label
Drug Resistance: Resistance of HSV and VZV to acyclovir can result from qualitative and quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of HSV and VZV with reduced susceptibility to acyclovir have been recovered from immunocompromised patients, especially with advanced HIV infection The possibility of viral resistance to acyclovir should be considered in patients who show poor clinical response during therapy.
Yes, a 71-year-old immunocompromised patient with Herpes Simplex Virus-1 (HSV-1) Encephalitis can develop resistance to Acyclovir after 15 days of treatment, complicated by intracranial hemorrhage and pneumonia.
- The development of resistance is more likely in immunocompromised patients 1.
- Resistance can occur due to changes in the viral thymidine kinase (TK) and/or DNA polymerase 1.
- Patients showing poor clinical response during therapy should be considered for potential viral resistance to acyclovir 1 and 1.
From the Research
Yes, it is possible that a 71-year-old immunocompromised patient with HSV-1 encephalitis who develops a brain bleed and pneumonia on day 15 of acyclovir treatment could have developed viral resistance. Acyclovir resistance occurs in approximately 5-10% of immunocompromised patients receiving prolonged therapy, as noted in a study published in 2024 2. In this situation, the clinical deterioration (brain bleed and pneumonia) might be complications of the infection not responding adequately to treatment. The healthcare team should consider obtaining CSF samples for HSV resistance testing and consider switching to alternative antivirals like foscarnet (40-60 mg/kg IV every 8 hours) or cidofovir (5 mg/kg once weekly) while awaiting results, as suggested by a multicenter assessment published in 2024 3. Resistance typically develops through mutations in the viral thymidine kinase gene, which prevents acyclovir from being activated within infected cells, as reported in a case study published in 2017 4. Immunocompromised patients are particularly vulnerable to developing resistant strains due to higher viral loads and prolonged viral replication. The brain bleed could be related to hemorrhagic encephalitis, while the pneumonia might represent either a secondary bacterial infection or HSV pneumonitis, both of which can occur in patients not responding to initial therapy. Key considerations in managing this patient include:
- Monitoring for signs of treatment failure or resistance
- Promptly switching to alternative antivirals if resistance is suspected
- Managing complications such as brain bleed and pneumonia aggressively
- Considering the use of foscarnet or cidofovir as alternative treatments, as supported by a study published in 2024 3. Overall, the management of acyclovir-resistant HSV infection requires a comprehensive approach that takes into account the patient's immunocompromised status, the risk of resistance, and the potential for complications.