title: Long-term valacyclovir suppressive treatment after herpes simplex virus type 2 meningitis: a double-blind, randomized controlled trial.
abstract: BACKGROUND
  Herpes simplex virus type 2 (HSV-2) is a common cause of acute and recurrent aseptic meningitis. Our aim was to determine the impact of antiviral suppression on recurrence of meningitis and to delineate the full spectrum of neurological complications.
  
  
  METHODS
  One hundred and one patients with acute primary or recurrent HSV-2 meningitis were assigned to placebo (n = 51) or 0.5 g of valacyclovir twice daily (n = 50) for 1 year after initial treatment with 1 g of valacyclovir 3 times daily for 1 week in a prospective, placebo-controlled, multicenter trial. The primary outcome was time until recurrence of meningitis. The patients were followed up for 2 years.
  
  
  RESULTS
  The first year, no significant difference was found between the valacyclovir and placebo groups. The second year, without study drugs, the risk of recurrence of verified and probable HSV-2 meningitis was significantly higher among patients exposed to valacyclovir (hazard ratio, 3.29 [95% confidence interval, 10.06-10.21]). One-third of the patients experienced 1-4 meningitis episodes during the study period. A considerable morbidity rate, comprising symptoms from the central, peripheral, and autonomous nervous system, was found in both groups.
  
  
  CONCLUSIONS
  Suppressive treatment with 0.5 g of valacyclovir twice daily was not shown to prohibit recurrent meningitis and cannot be recommended for this purpose after HSV meningitis in general. Protection against mucocutaneous lesions was observed, but the dosage was probably inappropriate for the prevention of HSV activation in the central nervous system. The higher frequency of meningitis, after cessation of active drug, could be interpreted as a rebound phenomenon.
authors.affiliation: Infectious Diseases Unit, Karolinska Institutet, [corrected] Karoliniska University Hospital, Stockholm, Sweden. elisabeth.aurelius@ki.se
authors.forename: E
authors.initials: E
authors.lastname: Aurelius
authors.forename: E
authors.initials: E
authors.lastname: Franzen-Röhl
authors.forename: M
authors.initials: M
authors.lastname: Glimåker
authors.forename: O
authors.initials: O
authors.lastname: Akre
authors.forename: L
authors.initials: L
authors.lastname: Grillner
authors.forename: C
authors.initials: C
authors.lastname: Jorup-Rönström
authors.forename: M
authors.initials: M
authors.lastname: Studahl
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006561:Herpes Simplex / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D008297:Male; D008587:Meningitis, Viral / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D011446:Prospective Studies; D055502:Secondary Prevention; D013548:Sweden; D016896:Treatment Outcome; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir