An HIV positive man has extensive perianal ulceration from herpes simplex virus unresponsive to high-dose acyclovir for 10 days. Genotyping shows thymidine kinase deficient virus. The most appropriate next agent is:

• A Valacyclovir at double dose
• B Ganciclovir
• C Foscarnet ✓
• D Penciclovir cream

Explanation

Acyclovir requires phosphorylation by viral thymidine kinase to its active triphosphate, so TK-deficient mutants are cross resistant to all guanine analogue prodrugs including valacyclovir and penciclovir. Foscarnet inhibits the viral DNA polymerase pyrophosphate binding site directly and needs no enzymatic activation, making it standard therapy for acyclovir resistant mucocutaneous HSV in AIDS. Its limiting toxicities are nephrotoxicity and ionised calcium chelation causing hypocalcaemia.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.