Valtrex or valacyclovir
Methylprednisolone, valacyclovir, or the combination for vestibular neuritis.

Brandt T.

Department of Neurology, University of Munich, Munich, Germany. mstrupp nefo.med.uni-muenchen.de

BACKGROUND: Vestibular neuritis is the second most common cause of peripheral vestibular vertigo. Its assumed cause is a reactivation of herpes simplex virus type 1 infection. Therefore, corticosteroids, antiviral agents, or a combination of the two might improve the outcome in patients with vestibular neuritis. METHODS: We performed a prospective, randomized, double-blind, two-by-two factorial trial in which patients with acute vestibular neuritis were randomly assigned to treatment with placebo, methylprednisolone, valacyclovir, or methylprednisolone plus valacyclovir. Vestibular function was determined by caloric irrigation, with the use of the vestibular paresis formula (to measure the extent of unilateral caloric paresis) within 3 days after the onset of symptoms and 12 months afterward. RESULTS: Of a total of 141 patients who underwent randomization, 38 received placebo, 35 methylprednisolone, 33 valacyclovir, and 35 methylprednisolone plus valacyclovir. At the onset of symptoms there was no difference among the groups in the severity of vestibular paresis. The mean (+/-SD) improvement in peripheral vestibular function at the 12-month follow-up was 39.6+/-28.1 percentage points in the placebo group, 62.4+/-16.9 percentage points in the methylprednisolone group, 36.0+/-26.7 percentage points in the valacyclovir group, and 59.2+/-24.1 percentage points in the methylprednisolone-plus-valacyclovir group. Analysis of variance showed a significant effect of methylprednisolone (P<0.001) but not of valacyclovir (P=0.43). The combination of methylprednisolone and valacyclovir was not superior to corticosteroid monotherapy. CONCLUSIONS: Methylprednisolone significantly improves the recovery of peripheral vestibular function in patients with vestibular neuritis, whereas valacyclovir does not. Copyright 2004 Massachusetts Medical Society

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Valtrex or valacyclovir
Valacyclovir treatment ameliorates the persistently increased pentylenetetrazol-induced seizure susceptibility in mice with herpes simplex virus type 1 infection.

Hsu KS.

Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan 701, Taiwan.

Herpes simplex virus type 1 (HSV-1) is an important pathogen related to epilepsy. We have shown previously that corneal inoculation of mice with HSV-1 causes acute spontaneous behavioral and electrophysiological seizures and increases hippocampal excitability and kainite-induced seizure susceptibility. In this study, we aimed to determine whether early-life HSV-1 infection in mice might cause short- and long-term enhanced susceptibility to pentylenetetrazol (PTZ)-induced seizures and to evaluate whether early antiviral drug therapy was effectively ameliorating this deficit. Seizure threshold was calculated by the latency of onset of the myoclonic jerk, generalized clonus, and maximal tonic-clonic convulsion. We demonstrate that the localization of viral antigens was predominantly within the bilateral temporal areas (amygdala, piriform, and entorhinal cortex) of HSV-1-infected mice. We also present evidence that mice of all HSV-1-infected groups had a shorter latency and higher severity to PTZ-induced seizures than in age-matched, mock-infected controls. Treatment of HSV-1-infected mice with valacyclovir, a potent inhibitor of HSV-1 replication, produced a dose-dependent decrease in the signs of neurological deficits, pathological damages, and PTZ-induced seizure severity. Our results are consistent with the hypothesis that early-life HSV-1 infection leads to persistent enhancement of neuronal excitability in limbic circuits, which could result in an overall increased propensity to induce seizures later in life. Additionally, prompt optimal antiviral therapy effectively decreases seizure susceptibility in HSV-1-infected mice by limiting the level of viral replication and inflammatory response induced by virus. The present study provides not only experimental evidence, but also a new therapeutic strategy in HSV-1-associated human epilepsy.

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Valtrex or valacyclovir
Valacyclovir and acyclovir for suppression of shedding of herpes simplex virus in the genital tract.

Corey L.

Department of Medicine, University of Washington, Seattle, Washington 98122, USA. rachnag u.washington.edu.

BACKGROUND: Valacyclovir exhibits better oral absorption and higher, more prolonged serum concentrations than oral acyclovir. The efficacy of valacyclovir and acyclovir on genital herpes simplex virus (HSV) shedding was assessed in a double-blind, 3-period crossover trial. METHODS: Sixty-nine immunocompetent participants with genital HSV-2 received oral valacyclovir, acyclovir, and matching placebo in random order for 7-week periods. Participants provided daily genital mucosal swabs for HSV detection by viral culture and polymerase chain reaction (PCR). RESULTS: HSV was detected at least once in 62 (90%) participants by culture and in 68 (98%) by PCR. During placebo, the total HSV shedding rate was 15.4% of days by culture (PCR, 40.2%); the subclinical shedding rate was 6.6% by culture (PCR, 27.1%). Both antivirals were associated with lower HSV shedding by culture (relative risk [RR], 0.03 [95% confidence interval [CI], 0.01-0.07] for valacyclovir and RR, 0.05 [95% CI, 0.03-0.10] for acyclovir) and PCR (RR, 0.18 [95% CI, 0.12-0.26] for valacyclovir and RR, 0.20 [95% CI, 0.15-0.28] for acyclovir), compared with placebo. No significant differences in frequency and quantity of HSV were detected by PCR between the valacyclovir and acyclovir arms. CONCLUSIONS: Although the suppression of viral replication is not complete, valacyclovir and acyclovir are highly effective in suppressing the frequency and quantity of genital HSV shedding. Copyright 2004 Infectious Diseases Society of America

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Valtrex or valacyclovir
Review of antiviral therapy for herpes labialis, genital herpes and herpes zoster.

Wendel KA.

Oklahoma University Health Science Center Department of Internal Medicine, Section Infectious Diseases, Oklahoma City, OK, USA.

Acyclovir (Zovirax) was approved for the treatment of herpesvirus infections almost two decades ago. It was the first agent in a novel group of antiviral medications that now include valacyclovir (Valtrex), penciclovir (Denavir and famciclovir (Famvir). These agents have made a dramatic impact on the morbidity associated with herpes simplex virus infections and herpes zoster. Topical and oral antiviral use have shown modest but statistically significant efficacy in treating herpes labialis with most studies demonstrating a significant reduction in episode length and/or healing time. Oral acyclovir, valacyclovir and famciclovir are efficacious and safe for the treatment of the first episode and recurrent genital herpes and are useful as suppressive therapy for individuals with frequent genital herpes recurrences. In addition, high doses of oral acyclovir, valacyclovir and famciclovir have been shown to speed the healing of herpes zoster, and data suggests that these agents also decrease associated acute and chronic pain in people of 50 years of age or older. Further research is required to clarify the safety of these agents in pregnant women with genital herpes, the role of antiviral therapy in decreasing the sexual transmission of genital herpes, and the efficacy and cost-effectiveness of these agents in treating herpes zoster in people below the age of 50 years.

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Valtrex or valacyclovir
Efficacy and safety of valacyclovir for the suppression and episodic treatment of herpes simplex virus in patients with HIV.

Brennan CA.

Westover Heights Clinic, 2330 NW Flanders, Ste. 207, Portland, OR 97210, USA. TWESTOVER aol.com

Three randomized controlled trials of valacyclovir for the management of recurrences of genital herpes in HIV-infected persons were conducted between 1991 and 2002. One study evaluated episodic therapy for the treatment of genital herpes, and 2 studies evaluated continuous suppressive therapy. Valacyclovir at 1000 mg twice daily for 5 days was comparable to acyclovir at 200 mg 5 times daily in accelerating healing of a single episode of genital herpes (hazard ratio, 1.0; 95% confidence interval [CI], 0.8-1.2; P=.89). Valacyclovir at 500 mg twice daily was effective in preventing or delaying recurrences of genital herpes compared with placebo (hazard ratio, 0.20; 95% CI, 0.13-0.30; P<.001) and with valacyclovir at 1000 mg once daily (hazard ratio, 0.56; 95% CI, 0.40-0.80; P=.001), in 6-month and 48-week studies, respectively. The safety profile of valacyclovir was similar to that of acyclovir. Valacyclovir is well tolerated, safe, and effective for the treatment and suppression of recurrent genital herpes in human immunodeficiency virus-infected persons.

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