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.
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Valacyclovir was tested in clinical trials for antiviral suppression of recurrence of meningitis, but treatment with valacyclovir twice daily did not prevent recurrent meningitis and was not recommended for this purpose.
“Valacyclovir was also tested in clinical trials for its antiviral suppression ability on recurrence of meningitis. However, treatment with valacyclovir (twice daily) did not prevent recurrent meningitis and was not recommended for this purpose [105, 106].”
From Viral meningitis: an overview (2021) · cites this paper as [105]
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Griffiths, P. D. (2018) · Reviews in Medical Virology · doi:10.1002/rmv.2015 · Cited by 1 · see citing works
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Clinical Characteristics in Herpes Simplex Virus 2 Meningitis in a Retrospective Single Center Study
Han, C., Kim, H., La, Y. K., Hwang, H., & Kim, W. (2016) · Journal of the Korean Neurological Association · doi:10.17340/jkna.2016.2.4
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Opportunistic Neurologic Infections in Patients Infected with Human Immunodeficiency Virus
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Nervous System Complications of Systemic Viral Infections
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MENINGOENCEFALITE VIRAL: O QUE O CLÍNICO PRECISA SABER?
Freitas, V. H. M., FREITAS, A. A. D., HERBESTE, E. A., Farias, J. P. B. D. A., CAVALCANTE, D. V., Nogueira, J. V. M., Cerqueira, G. S., PINHEIRO, M. D. A., & MOURA, A. E. F. (2023) · Editora Pasteur eBooks · doi:10.59290/978-65-6029-069-3.2
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Denominator and Workflow Dependence of Age-Specific Viral Detection in Cerebrospinal Fluid
Kim, J. Y., Kwon, H.-J., Jeon, J., & Kim, J. K. (2026) · Pathogens · doi:10.3390/pathogens15090905
- Authors
- Aurelius, E., Franzen-Rohl, E., Glimaker, M., Akre, O., Grillner, L., Jorup-Ronstrom, C., Studahl, M., & the HSV-2 Meningitis Study Group
- Affiliations
- Karolinska University Hospital (SE)
- Sahlgrenska University Hospital (SE)
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-03-28
- Volume
- 54
- Issue
- 9
- Pages
- 1304-1313
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- OpenAlex
- W2148635135
- Cited by
- 86
- References
- 35
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 10 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 7 · 2016: 6 · 2015: 10 · 2014: 4 · 2013: 3 · 2012: 2
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Keywords
- herpes simplex virus type 2, valacyclovir, suppressive antiviral therapy, recurrent meningitis, aseptic meningitis, neurological complications, mucocutaneous lesions, HSV reactivation
- MeSH terms
- Valacyclovir, Acyclovir, Adult, Antiviral Agents, Double-Blind Method, Female, Follow-Up Studies, Herpes Simplex, Humans, Male, Meningitis, Viral, Prospective Studies, Sweden, Valine, Treatment Outcome, Herpesvirus 2, Human, Secondary Prevention
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