Efficacy of the early administration of valacyclovir hydrochloride for the treatment of neuropathogenic equine herpesvirus type-1 infection in horses

Abstract

OBJECTIVE To determine whether prophylactic administration of valacyclovir hydrochloride versus initiation of treatment at the onset of fever would differentially protect horses from viral replication and clinical disease attributable to equine herpesvirus type-1 (EHV-1) infection. ANIMALS 18 aged mares. PROCEDURES Horses were randomly assigned to receive an oral placebo (control), treatment at detection of fever, or prophylactic treatment (initiated 1 day prior to viral challenge) and then inoculated intranasally with a neuropathogenic strain of EHV-1. Placebo or valacyclovir was administered orally for 7 or 14 days after EHV-1 inoculation or detection of fever (3 horses/group). Effects of treatment on viral replication and clinical disease were evaluated. Plasma acyclovir concentrations and viremia were assessed to determine inhibitory concentrations of valacyclovir. RESULTS Valacyclovir administration decreased shedding of virus and viremia, compared with findings for control horses. Rectal temperatures and clinical disease scores in horses that received valacyclovir prophylactically for 2 weeks were lower than those in control horses. The severity of but not the risk for ataxia was decreased by valacyclovir administration. Viremia was decreased when steady-state trough plasma acyclovir concentrations were > 0.8 μg/mL, supporting the time-dependent activity of acyclovir. CONCLUSIONS AND CLINICAL RELEVANCE Valacyclovir treatment significantly decreased viral replication and signs of disease in EHV-1-infected horses; effects were greatest when treatment was initiated before viral inoculation, but treatment was also effective when initiated as late as 2 days after inoculation. During an outbreak of equine herpesvirus myeloencephalopathy, antiviral treatment may be initiated in horses at various stages of infection, including horses that have not yet developed signs of viral disease.

Effect of valacyclovir on EHV‐5 viral kinetics in horses with equine multinodular pulmonary fibrosis

“…The study was designed as a prospective clinical trial during which horses diagnosed with EMPF would undergo 10 days of treatment with PO administered valacyclovir. This duration of valacyclovir treatment was selected based on previous evidence that 1–2 weeks of PO administered valacyclovir treatment was sufficient to decrease viremia and virus shedding of EHV‐1 in horses . Throughout treatment, the viral load of EHV‐5 was measured via qPCR of blood, NS and BALF.…”

“…After oral administration, the prodrug valacyclovir is promptly hydrolysed to acyclovir, an inhibitor of viral DNA polymerase. Valacyclovir has been used both prophylactically and therapeutically in equine herpesvirus‐1 (EHV‐1) outbreaks to decrease viremia and virus shedding . Treatment of horses with PO administered valacyclovir is relatively expensive and to the authors’ knowledge, there are currently no studies investigating the effect of valacyclovir on EHV‐5 viral kinetics in horses with EMPF.…”

“…The objective of our study was to determine the effect of oral administration of valacyclovir on qPCR EHV‐5 viral kinetics on blood, NS and BALF in horses with EMPF. Plasma samples collected during the maintenance phase of treatment were analyzed by high performance liquid chromatography (HPLC) to ensure the acyclovir concentrations obtained were comparable to previous studies …”

Acyclovir inhibits Cyprinid herpesvirus 3 multiplication in vitro

“…Recently, Maxwell et al. () carried out more comprehensive study on the EHV‐1‐infected mares. The outcomes indicated that the valACV decreases viral replication and severity of the disease.…”

“…Similarly, studies on the ACV activities against Equid herpesvirus 1 (EHV-1) demonstrated that the ACV indicates an anti-EHV-1 effect in equine embryonic lung (EEL) cells , but further in vivo study with the use of the valACV failed to confirm these findings (Garré, Gryspeerdt, Croubels, De Backer, & Nauwynck, 2009). Recently, Maxwell et al (2017) carried out more comprehensive study on the EHV-1-infected mares. The outcomes indicated that the valACV decreases viral replication and severity of the disease.…”