title: Evaluation of the effect of short-term treatment with the integrase inhibitor raltegravir (Isentress) on the course of progressive feline leukemia virus infection.
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 20mg then 40mg 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 (40mg then 80mg 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. (250 words).
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland. Electronic address: andieboesch@gmail.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Boesch
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland. Electronic address: valentino.cattori@gmail.com.
authors.forename: Valentino
authors.initials: V
authors.lastname: Cattori
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland. Electronic address: briond@vetclinics.uzh.ch.
authors.forename: Barbara
authors.initials: B
authors.lastname: Riond
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland; Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland. Electronic address: bwilli@vetclinics.uzh.ch.
authors.forename: Barbara
authors.initials: B
authors.lastname: Willi
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland. Electronic address: mmeli@vetclinics.uzh.ch.
authors.forename: Marina L
authors.initials: ML
authors.lastname: Meli
authors.affiliation: Institute of Clinical Chemistry, University Hospital, Raemistrasse 100, 8091 Zurich, Switzerland. Electronic address: katharina.rentsch@usb.ch.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Rentsch
authors.affiliation: Medical Research Council, University of Glasgow Centre for Virus Research, Henry Wellcome Building for Comparative Medical Sciences, 464 Bearsden Road, Glasgow G61 1QH, UK. Electronic address: margaret.hosie@glasgow.ac.uk.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Hosie
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland. Electronic address: rhofmann@vetclinics.uzh.ch.
authors.forename: Regina
authors.initials: R
authors.lastname: Hofmann-Lehmann
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland. Electronic address: hlutz@vetclinics.uzh.ch.
authors.forename: Hans
authors.initials: H
authors.lastname: Lutz
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D002415:Cats; D005256:Leukemia Virus, Feline / Q000235:genetics; D016582:Leukemia, Feline / Q000188:drug therapy*; D008223:Lymphoma; D012367:RNA, Viral / Q000235:genetics; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms; D019562:Viral Load; D014766:Viremia; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D000068898:Raltegravir Potassium
keywords: Antiretroviral therapy; Feline leukemia virus; Immune response, raltegravir; Retrovirus; Viral loads