Herpes simplex virus type 2 meningoencephalitis resistant to acyclovir in a patient with AIDS

A case is reported of relapsing fatal meningoencephalitis caused by a neurovirulent thymidine kinase-positive (TK⁺) type 2 herpes simplex virus (HSV) that developed thymidine kinase deficiency (TK^-) during intravenous acyclovir therapy. A patient with AIDS was admitted for acyclovir treatment of a persistent perirectal herpetic ulcer. He subsequently developed meningoencephalitis. A TK⁺ type 2 HSV was isolated from a brain biopsy specimen. A progressive and fatal relapse occurred, and a TK^- type 2 HSV was isolated from his cerebrospinal fluid. Restriction endonuclease analysis of viral DNA from perianal, brain, and cerebrospinal fluid isolates were similar, suggesting that they were the same viral strain. Animal virulence studies indicated significant cutaneous virulence in immunocompromised mice models for the TK^- isolates. This case is notable because TK^- HSV have, in the past, lacked neurovirulence and because acyclovir resistance developed during therapy and caused the patient's death.