Vidarabine versus Acyclovir Therapy in Herpes Simplex Encephalitis

Abstract

We randomly assigned 208 patients who underwent brain biopsy for presumptive herpes simplex encephalitis to receive either vidarabine (15 mg per kilogram of body weight per day) or acyclovir (30 mg per kilogram per day) for 10 days. Sixty-nine patients (33 percent) had biopsy-proved disease; 37 received vidarabine, and 32 acyclovir. The mortality in the vidarabine recipients was 54 percent, as compared with 28 percent in the acyclovir recipients (P = 0.008). Six-month mortality varied according to the Glasgow coma score at the onset of therapy. For scores of greater than 10, 7 to 10, and less than or equal to 6, mortality was 42, 46, and 67 percent in the patients treated with vidarabine, as compared with 0, 25, and 25 percent in those treated with acyclovir. A six-month morbidity assessment using an adapted scoring system revealed that 5 of 37 patients receiving vidarabine (14 percent) as compared with 12 of 32 receiving acyclovir (38 percent) were functioning normally (P = 0.021). Eight vidarabine-treated patients (22 percent) and three acyclovir-treated patients (9 percent) had moderate debility. Patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acyclovir treatment. We conclude that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis.

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

“…The mortality of untreated HSV encephalitis is roughly 70 %, and 97 % of survivors will not return to their previous level of function [41,[154][155][156]. Clinical trials in the 1980s demons t r a t e d s i g n i f i c a n t l y i m p r o v e d o u t c o m e s w i t h intravenous aciclovir, as described above [103,104], and the 1-year mortality with current antivirals and supportive care is now in the range of 5-15 %, despite high rates of admission to the ICU [44,60,157]. However, consequent neuropsychiatric deficits remain common (69-89 %) [60,157].…”

Persistence of herpes simplex virus DNA in cerebrospinal fluid of neonates with herpes simplex virus encephalitis

“…[13][14][15] These patients had participated in several randomized, placebo-controlled trials of iodoxouridine, vidarabine or acyclovir, the latter provided at a dose of 30 mg kg À1 per day. During the first week of antiviral therapy, 49 (98%) of 50 CSF specimens from 39 patients were HSV DNA-positive by PCR.…”

Clinical Trials in Neurovirology: Successes, Challenges, and Pitfalls

“…Subsequent research turned to vidarabine, which proved to have benefit when compared with placebo [2]. However, the still poor outcomes stimulated ongoing research, with 2 major comparative studies between vidarabine and aciclovir, and both demonstrating clear superiority of aciclovir [3,4]. This has remained the standard of care over the last 30 years.…”

“…Only if the study sample has the condition studied at a stage where irreparable brain damage has not yet occurred can one hope to test therapeutics. The early trials for HSV were challenged by requiring brain biopsy diagnosis in cases where a clinically suspect patient was considered for the trial [1][2][3]. In spite of the complexity and risk of brain biopsy, without an alternative secure means of diagnosis, it was necessary because clinical diagnosis was only correct in roughly half of cases.…”