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.

CLINICAL TRIALS REGISTRATION:

NCT00031486.

• Authors: John W Gnann Jr, Birgit Sköldenberg, John Hart, Elisabeth Aurelius, Silvia Schliamser, Marie Studahl, Britt-Marie Eriksson, Daniel Hanley, Fred Aoki, Alan C Jackson, Paul Griffiths, Lil Miedzinski, Diane Hanfelt-Goade, Daniel Hinthorn, Clas Ahlm, Allen Aksamit, Salvador Cruz-Flores, Ilet Dale, Gretchen Cloud, Penelope Jester, Richard J Whitley, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 61 Issue 5 Pg. 683-91 (Sep 01 2015) ISSN: 1537-6591 [Electronic] United States
• PMID: 25956891 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Antiviral Agents
• Valine
• Valacyclovir
• Acyclovir

Topics

• Acyclovir (administration & dosage, analogs & derivatives, therapeutic use)
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antiviral Agents (administration & dosage, therapeutic use)
• Cognition Disorders
• Encephalitis, Herpes Simplex (drug therapy, epidemiology, physiopathology)
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Quality of Life
• Valacyclovir
• Valine (administration & dosage, analogs & derivatives, therapeutic use)
• Young Adult