title: Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir Therapy.
abstract: BACKGROUND
  Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority.
  
  
  METHODS
  Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint.
  
  
  RESULTS
  The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group.
  
  
  CONCLUSIONS
  Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors.
  
  
  BACKGROUND
  NCT00031486.
authors.affiliation: University of Alabama at Birmingham.
authors.forename: John W
authors.initials: JW
authors.lastname: Gnann
authors.affiliation: Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Birgit
authors.initials: B
authors.lastname: Sköldenberg
authors.affiliation: University of Texas at Dallas.
authors.forename: John
authors.initials: J
authors.lastname: Hart
authors.affiliation: Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Aurelius
authors.affiliation: Skåne University Hospital, Lund.
authors.forename: Silvia
authors.initials: S
authors.lastname: Schliamser
authors.affiliation: Gothenburg University.
authors.forename: Marie
authors.initials: M
authors.lastname: Studahl
authors.affiliation: Uppsala University, Sweden.
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Eriksson
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hanley
authors.affiliation: University of Manitoba, Winnipeg.
authors.forename: Fred
authors.initials: F
authors.lastname: Aoki
authors.affiliation: Queen's University, Kingston, Ontario, Canada.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Jackson
authors.affiliation: University College London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Griffiths
authors.affiliation: University of Alberta Hospital, Edmonton, Canada.
authors.forename: Lil
authors.initials: L
authors.lastname: Miedzinski
authors.affiliation: University of New Mexico, Albuquerque.
authors.forename: Diane
authors.initials: D
authors.lastname: Hanfelt-Goade
authors.affiliation: University of Kansas, Kansas City.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hinthorn
authors.affiliation: Umeå University, Sweden.
authors.forename: Clas
authors.initials: C
authors.lastname: Ahlm
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Allen
authors.initials: A
authors.lastname: Aksamit
authors.affiliation: St Louis University, Missouri.
authors.forename: Salvador
authors.initials: S
authors.lastname: Cruz-Flores
authors.affiliation: University of Alabama at Birmingham.
authors.forename: Ilet
authors.initials: I
authors.lastname: Dale
authors.affiliation: University of Alabama at Birmingham.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Cloud
authors.affiliation: University of Alabama at Birmingham.
authors.forename: Penelope
authors.initials: P
authors.lastname: Jester
authors.affiliation: University of Alabama at Birmingham.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whitley
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003072:Cognition Disorders; D020803:Encephalitis, Herpes Simplex / Q000188:drug therapy* / Q000453:epidemiology* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir
keywords: acyclovir; antiviral therapy; encephalitis; herpes simplex virus; valacyclovir