Evaluation of the effect of short-term treatment with the integrase inhibitor raltegravir (Isentress™) on the course of progressive feline leukemia virus infection

Boesch, A., Cattori, V., Riond, B., Willi, B., Meli, M. L., Rentsch, K. M., Hosie, M. J. , Hofmann-Lehmann, R. and Lutz, H. (2015) Evaluation of the effect of short-term treatment with the integrase inhibitor raltegravir (Isentress™) on the course of progressive feline leukemia virus infection. Veterinary Microbiology, 175(2-4), pp. 167-178. (doi: 10.1016/j.vetmic.2014.10.031) (PMID:25500005)

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Abstract

Cats persistently infected with the gammaretrovirus feline leukemia virus (FeLV) are at risk to die within months to years from FeLV-associated disease, such as immunosuppression, anemia or lymphoma/leukemia. The integrase inhibitor raltegravir has been demonstrated to reduce FeLV replication in vitro. The aim of the present study was to investigate raltegravir in vivo for its safety and efficacy to suppress FeLV replication. The safety was tested in three naïve specified pathogen-free (SPF) cats during a 15 weeks treatment period (initially 20 mg then 40 mg orally b.i.d.). No adverse effects were noted. The efficacy was tested in seven persistently FeLV-infected SPF cats attained from 18 cats experimentally exposed to FeLV-A/Glasgow-1. The seven cats were treated during nine weeks (40 mg then 80 mg b.i.d.). Raltegravir was well tolerated even at the higher dose. A significant decrease in plasma viral RNA loads (∼5×) was found; however, after treatment termination a rebound effect was observed. Only one cat developed anti-FeLV antibodies and viral RNA loads remained decreased after treatment termination. Of note, one of the untreated FeLV-A infected cats developed fatal FeLV-C associated anemia within 5 weeks of FeLV-A infection. Moreover, progressive FeLV infection was associated with significantly lower enFeLV loads prior to infection supporting that FeLV susceptibility may be related to the genetic background of the cat. Overall, our data demonstrate the ability of raltegravir to reduce viral replication also in vivo. However, no complete control of viremia was achieved. Further investigations are needed to find an optimized treatment against FeLV.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hosie, Professor Margaret
Authors: Boesch, A., Cattori, V., Riond, B., Willi, B., Meli, M. L., Rentsch, K. M., Hosie, M. J., Hofmann-Lehmann, R., and Lutz, H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Veterinary Microbiology
Publisher:Elsevier B.V.
ISSN:0378-1135
ISSN (Online):1873-2542
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