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After IV acyclovir, adjunctive oral valacyclovir has no benefit in HSV encephalitis
After a standard course of IV acyclovir therapy for laboratory-confirmed herpes simplex encephalitis, further treatment with 3 months of oral valacyclovir does not appear to confer additional benefit among relatively high-functioning patients, according to recent data.
In the double-blind, placebo controlled trial, researchers evaluated 87 adults with PCR-confirmed herpes simplex encephalitis. After standard treatment with 14 days to 21 days of IV acyclovir, participants were randomly assigned to a 90-day course of either 2g valacyclovir, three times daily (n = 40), or placebo (n = 47).
The researchers defined the study’s primary endpoint as survival with no or mild neuropsychological impairment at 12 months, which was evaluated using the Mattis Dementia Rating Scale (MDRS). Secondary endpoints were survival with no or mild neuropsychological impairment, measured by the Mini-Mental State Examination and the Glasgow Coma Scale, at 90 days and 6 months, 12 months and 24 months. The 36-item Short-Form Health Survey (SF-36) was used to assess the effect of valacyclovir treatment on quality of life.
The researchers found that at 90 days, 89% of patients in the valacyclovir group and 81% of placebo participants had no or mild impairment (MDRS score: 121-144). At 12 months, 86% of participants in the valacyclovir group and 90% of participants in the placebo group had no or mild impairment (P = .72). These figures did not change between 12 months and 24 months of follow-up. Neither group demonstrated significant study-related adverse events.
In a related editorial, Kenneth L. Tyler, MD, of the Departments of Neurology, Medicine, and Immunology-Microbiology, University of Colorado School of Medicine, Aurora, noted that there are several promising anti-HSV agents being developed, such as the orally bioavailable lipid conjugate of cidofovir, CMX001. He added that the overall positive outcomes attained by the patient population in this study are encouraging.
“Negative results are always discouraging,” Tyler wrote. “As the authors note, this study did provide several intriguing insights into the outcome of [herpes simplex encephalitis] in the modern era. It was quite remarkable how well this selected population of subjects actually did.
“By 2 years post-illness, 91% of the subjects had no or mild impairment on the [Mini-Mental State Examination] and 90% had no or mild impairment on the MDRS. The bulk of the improvement on these tests from baseline occurred within the first 90 days.”
Disclosure: Gnann reports receiving research grants from the NIH and personal fees from Merck BioCryst and GlaxoSmithKline. Tyler reports no relevant financial disclosures. Please see the full study for a complete list of all other authors’ disclosures.
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Tyler KL. Clin Infect Dis. 2015; DOI: 10.1093/cid/civ373.