An immunocompromised patient receiving chronic acyclovir suppressive therapy develops progressive mucocutaneous herpes simplex lesions despite adequate dosing. The most common molecular mechanism of resistance in this setting is:

• A Loss of viral thymidine kinase expression or substrate specificity ✓
• B Mutation of the viral DNA polymerase gene
• C Upregulation of multidrug efflux pumps in infected cells
• D Increased degradation of acyclovir triphosphate by viral pyrophosphatase

Explanation

Acyclovir requires initial phosphorylation by viral thymidine kinase to the monophosphate before host kinases complete activation. Most clinically significant resistance arises from TK-deficient or TK-altered mutants, common in immunocompromised hosts on prolonged therapy. Such mutants are cross-resistant to valacyclovir and famciclovir, and foscarnet, needing no kinase activation, becomes the fallback agent.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.