Herpes simplex virus 1 infection and valacyclovir treatment in schizophrenia: Results from the VISTA study

Abstract Background Several studies have implicated herpes simplex virus-type 1 (HSV-1) in the pathophysiology of schizophrenia. A recent trial demonstrated that the anti-viral medication valacylovir, which prevents replication of activated HSV-1, improved selected cognitive deficits in people with schizophrenia. In this study, we examined demographic and illness related differences between HSV-1 positive versus HSV-1 negative subjects with early phase schizophrenia and attempted to replicate the previous valacyclovir treatment results in this population. Methods 170 subjects with schizophrenia (HSV-1 positive N = 70; HSV-1 negative N = 96) from 12 US sites participated in the HSV-1 positive versus negative comparisons, and were randomized 1:1 to valacyclovir (1.5 g BID) or placebo for a 16-week, double-blind efficacy trial. The primary endpoints were working and verbal memory. Results The HSV-1 positive group, as compared to the HSV-1 negative group, were older (p  Conclusions HSV-1 sero-positivity appears to be a marker of a subgroup with a more severe form of schizophrenia. Valacyclovir was not efficacious in the study, perhaps because the herpes virus was in the dormant, non-activated state and therefore non-responsive to valacyclovir effects. ClinicalTrials.gov Identifier: NCT02008773