Antiviral therapy in cats progressively infected with feline leukaemia virus: lessons from a series of 18 consecutive cases from Australia.
FeLV
antiviral
field study
retroviral infection
vaccination
veterinary science
Journal
Australian veterinary journal
ISSN: 1751-0813
Titre abrégé: Aust Vet J
Pays: England
ID NLM: 0370616
Informations de publication
Date de publication:
23 Jul 2024
23 Jul 2024
Historique:
revised:
23
06
2024
received:
15
12
2023
accepted:
03
07
2024
medline:
23
7
2024
pubmed:
23
7
2024
entrez:
23
7
2024
Statut:
aheadofprint
Résumé
It is doubtful that any of the treatments proposed for feline leukaemia virus (FeLV) infection are effective, despite the entity being described 60 years ago. Eighteen pet cats with progressive FeLV infections were recruited in Australia. One or more antiviral drugs were trialled in 16 cats, while two FeLV-infected cats were not handleable and served as untreated controls. Six cats were administered RetroMAD1™ only (0.5 mg/kg orally twice daily), a commercially available recombinant chimeric protein with proposed antiretroviral activity. Three cats were administered the integrase inhibitor raltegravir only (10-15 mg/kg orally twice daily), a drug used as a component of highly effective antiretroviral therapy for human immunodeficiency virus (HIV-1) infection. Three cats were administered RetroMAD1™ and raltegravir concurrently, and four cats were administered raltegravir and the reverse transcriptase inhibitor zidovudine (AZT, 5 mg/kg orally twice daily) concurrently. FeLV RNA and p27 antigen loads were measured at two timepoints (T1-2 months and T3-5 months) during therapy and compared to baseline (pretreatment) levels, to assess the response to therapy using linear modelling. The median survival time (MST) of the cats from commencement of FeLV treatment to death was also determined and compared between treatments. The MST for the 16 FeLV-positive cats which received antiviral therapy was 634 days, while the MST from FeLV diagnosis to death for the two untreated control cats was 780 days. In cats treated with RetroMAD1™, FeLV viral load decreased from T0 to T1-2 months (median viral load reduced from 1339 × 10 Results from this small case series do not provide convincing support for the use of RetroMAD1™, raltegravir or AZT, alone or in combination, for the treatment of cats progressively infected with FeLV. The changes observed were biologically insignificant. Age and FeLV viral load at diagnosis are useful prognostic markers, and p27 antigen concentration can be used to predict viral load. Larger field trials should be performed examining antiretroviral therapy in FeLV-positive cats with progressive infections, preferably using three or more drugs from at least two classes, as is standard with human antiretroviral therapy. Future studies would be easier in countries with a higher prevalence of FeLV infections than Australia.
Sections du résumé
BACKGROUND
BACKGROUND
It is doubtful that any of the treatments proposed for feline leukaemia virus (FeLV) infection are effective, despite the entity being described 60 years ago.
METHODS
METHODS
Eighteen pet cats with progressive FeLV infections were recruited in Australia. One or more antiviral drugs were trialled in 16 cats, while two FeLV-infected cats were not handleable and served as untreated controls. Six cats were administered RetroMAD1™ only (0.5 mg/kg orally twice daily), a commercially available recombinant chimeric protein with proposed antiretroviral activity. Three cats were administered the integrase inhibitor raltegravir only (10-15 mg/kg orally twice daily), a drug used as a component of highly effective antiretroviral therapy for human immunodeficiency virus (HIV-1) infection. Three cats were administered RetroMAD1™ and raltegravir concurrently, and four cats were administered raltegravir and the reverse transcriptase inhibitor zidovudine (AZT, 5 mg/kg orally twice daily) concurrently. FeLV RNA and p27 antigen loads were measured at two timepoints (T1-2 months and T3-5 months) during therapy and compared to baseline (pretreatment) levels, to assess the response to therapy using linear modelling. The median survival time (MST) of the cats from commencement of FeLV treatment to death was also determined and compared between treatments.
RESULTS
RESULTS
The MST for the 16 FeLV-positive cats which received antiviral therapy was 634 days, while the MST from FeLV diagnosis to death for the two untreated control cats was 780 days. In cats treated with RetroMAD1™, FeLV viral load decreased from T0 to T1-2 months (median viral load reduced from 1339 × 10
CONCLUSIONS
CONCLUSIONS
Results from this small case series do not provide convincing support for the use of RetroMAD1™, raltegravir or AZT, alone or in combination, for the treatment of cats progressively infected with FeLV. The changes observed were biologically insignificant. Age and FeLV viral load at diagnosis are useful prognostic markers, and p27 antigen concentration can be used to predict viral load. Larger field trials should be performed examining antiretroviral therapy in FeLV-positive cats with progressive infections, preferably using three or more drugs from at least two classes, as is standard with human antiretroviral therapy. Future studies would be easier in countries with a higher prevalence of FeLV infections than Australia.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Australian Companion Animal Health Foundation
ID : 017/2014
Organisme : Australian Companion Animal Health Foundation
ID : 014/2017
Informations de copyright
© 2024 The Author(s). Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.
Références
Studer N, Lutz H, Saegerman C et al. Pan‐European study on the prevalence of the feline leukaemia virus infection – reported by the European advisory board on cat diseases (ABCD Europe). Viruses 2019;11(11):993.
Willett BJ, Hosie MJ. Feline leukaemia virus: half a century since its discovery. Vet J 2013;195(1):16–23.
O'Brien SJ, Troyer JL, Brown MA et al. Emerging viruses in the Felidae: shifting paradigms. Viruses 2012;4(2):236–257.
Jarrett W, Crawford E, Martin W et al. Leukaemia in the cat: a virus‐like particle associated with leukaemia (lymphosarcoma). Nature 1964;202(4932):567–568.
Levy JK, Scott HM, Lachtara JL et al. Seroprevalence of feline leukemia virus and feline immunodeficiency virus infection among cats in North America and risk factors for seropositivity. J Am Vet Med Assoc 2006;228(3):371–376.
Burling AN, Levy JK, Scott HM et al. Seroprevalences of feline leukemia virus and feline immunodeficiency virus infection in cats in the United States and Canada and risk factors for seropositivity. J Am Vet Med Assoc 2017;251(2):187–194.
Hofmann‐Lehmann R, Hartmann K. Feline leukaemia virus infection: a practical approach to diagnosis. J Feline Med Surg 2020;22(9):831–846.
Hartmann K, Hofmann‐Lehmann R. What's new in feline leukemia virus infection. Vet Clin North Am Small Anim Pract 2020;50(5):1013–1036.
Major A, Cattori V, Boenzli E et al. Exposure of cats to low doses of FeLV: seroconversion as the sole parameter of infection. Vet Res 2010;41(2):17.
Hofmann‐Lehmann R, Tandon R, Boretti FS et al. Reassessment of feline leukaemia virus (FeLV) vaccines with novel sensitive molecular assays. Vaccine 2006;24(8):1087–1094.
Lutz H, Pedersen NC, Theilen GH. Course of feline leukemia virus infection and its detection by enzyme‐linked immunosorbent assay and monoclonal antibodies. Am J Vet Res 1983;44(11):2054–2059.
Lutz H, Addie D, Belak S et al. Feline leukaemia: ABCD guidelines on prevention and management. J Feline Med Surg 2009;11(7):565–574.
Hartmann K. Clinical aspects of feline retroviruses: a review. Viruses 2012;4(11):2684–2710.
Hardy WD, Hess PW, MacEwen EG et al. Biology of feline leukemia virus in the natural environment. Cancer Res 1976;36(2 Part 2):582–588.
Helfer‐Hungerbuehler AK, Widmer S, Kessler Y et al. Long‐term follow up of feline leukemia virus infection and characterization of viral RNA loads using molecular methods in tissues of cats with different infection outcomes. Virus Res 2015;197:137–150.
Shelton GH, Grant CK, Cotter SM et al. Feline immunodeficiency virus and feline leukemia virus infections and their relationships to lymphoid malignancies in cats: a retrospective study (1968‐1988). J Acquir Immune Defic Syndr 1990;3(6):623–630.
Hoover EA, Zeidner NS, Mullins JI. Therapy of presymptomatic FeLV‐induced immunodeficiency syndrome with AZT in combination with alpha interferon. Ann N Y Acad Sci 1990;616:258–269.
Mathes L, Polas P, Hayes K et al. Pre‐and postexposure chemoprophylaxis: evidence that 3′‐azido‐3′‐dideoxythymidine inhibits feline leukemia virus disease by a drug‐induced vaccine response. Antimicrob Agents Chemother 1992;36(12):2715–2721.
Tavares L, Roneker C, Johnston K et al. 3′‐Azido‐3′‐deoxythymidine in feline leukemia virus‐infected cats: a model for therapy and prophylaxis of AIDS. Cancer Res 1987;47(12):3190–3194.
Tavares L, Roneker C, Postie L et al. Testing of nucleoside analogues in cats infected with feline leukemia virus: a model. Intervirology 1989;30(Suppl. 1):26–35.
Mukherji E, Au J, Mathes LE. Differential antiviral activities and intracellular metabolism of 3′‐azido‐3′‐deoxythymidine and 2′, 3′‐dideoxyinosine in human cells. Antimicrob Agents Chemother 1994;38(7):1573–1579.
Zeidner NS, Rose LM, Mathiason‐DuBard CK et al. Zidovudine in combination with alpha interferon and interleukin‐2 as prophylactic therapy for FeLV‐induced immunodeficiency syndrome (FeLV‐FAIDS). J Acquir Immune Defic Syndr 1990;3(8):787–796.
Zeidner NS, Myles MH, Mathiason‐DuBard CK et al. Alpha interferon (2b) in combination with zidovudine for the treatment of presymptomatic feline leukemia virus‐induced immunodeficiency syndrome. Antimicrob Agents Chemother 1990;34(9):1749–1756.
Stuetzer B, Brunner K, Lutz H et al. A trial with 3′‐azido‐2′, 3′‐dideoxythymidine and human interferon‐α in cats naturally infected with feline leukaemia virus. J Feline Med Surg 2013;15(8):667–671.
Wilkes RP, Hartmann K. Update on antiviral therapies. August's Consultations Feline Internal Med 2016;7:84–96.
deMari K, Maynard L, Sanquer A et al. Therapeutic effects of recombinant feline interferon‐w on feline leukemia virus (FeLV)‐infected and FeLV/feline immunodeficiency virus (FIV)‐coinfected symptomatic cats. J Vet Intern Med 2004;18(4):477–482.
Gomez‐Lucia E, Collado VM, Miró G et al. Clinical and hematological follow‐up of long‐term oral therapy with type‐I interferon in cats naturally infected with feline leukemia virus or feline immunodeficiency virus. Animals 2020;10(9):1464.
Doménech A, Miró G, Collado VM et al. Use of recombinant interferon omega in feline retrovirosis: from theory to practice. Vet Immunol Immunopathol 2011;143(3):301–306.
Gomez‐Lucia E, Collado VM, Miro G et al. Follow‐up of viral parameters in FeLV‐ or FIV‐naturally infected cats treated orally with low doses of human interferon alpha. Viruses 2019;11(9):845.
Gil S, Leal RO, Duarte A et al. Relevance of feline interferon omega for clinical improvement and reduction of concurrent viral excretion in retrovirus infected cats from a rescue shelter. Res Vet Sci 2013;94(3):753–763.
Cattori V, Weibel B, Lutz H. Inhibition of feline leukemia virus replication by the integrase inhibitor Raltegravir. Vet Microbiol 2011;152(1–2):165–168.
Boesch A, Cattori V, Riond B et al. Evaluation of the effect of short‐term treatment with the integrase inhibitor raltegravir (Isentress) on the course of progressive feline leukemia virus infection. Vet Microbiol 2015;175(2–4):167–178.
Santos C, Ferreira IT, Beranger R et al. Undetectable proviral DNA and viral RNA levels after raltegravir administration in two cats with natural feline leukemia virus infection. Braz J Vet Med 2022;44:e003522.
Zenchenkova AP, Vatnikov YA. Efficacy of COP‐based protocol used with raltegravir in treatment of cats with mediastinal lymphoma and progressive viral leukemia. RUDN J Agron Anim Indust 2023;18(3):411–417.
Huan UE, Da Silva PMF, Floriano AP. Case studies on RetroMAD1™, an orally administered recombinant chimeric protein to treat naturally infected feline leukemia virus (FeLV) cats. Arch Vet Sci Med 2019;2(4):41–57.
https://www.abcdcatsvets.org/guideline-for-feline-leukaemia-virus-infection/.
Tandon R, Cattori V, Gomes‐Keller MA et al. Quantitation of feline leukaemia virus viral and proviral loads by TaqMan real‐time polymerase chain reaction. J Virol Methods 2005;130(1–2):124–132.
Westman M, Norris J, Malik R et al. The diagnosis of feline leukaemia virus (FeLV) infection in owned and group‐housed rescue cats in Australia. Viruses 2019;11(6):503.
Lutz H, Pedersen NC, Durbin R et al. Monoclonal antibodies to three epitopic regions of feline leukemia virus p27 and their use in enzyme‐linked immunosorbent assay of p27. J Immunol Methods 1983;56(2):209–220.
Hofmann‐Lehmann R, Huder JB, Gruber S et al. Feline leukaemia provirus load during the course of experimental infection and in naturally infected cats. J Gen Virol 2001;82(7):1589–1596.
Stone AE, Brummet GO, Carozza EM et al. 2020 AAHA/AAFP Feline Vaccination Guidelines. J Feline Med Surg 2020;22(9):813–830.
Squires RA, Crawford C, Marcondes M et al. 2024 guidelines for the vaccination of dogs and cats – compiled by the vaccination guidelines group (VGG) of the world small animal veterinary association (WSAVA). J Small Anim Pract 2024;65(5):277–316.
Beall MJ, Buch J, Clark G et al. Feline leukemia virus p27 antigen concentration and proviral DNA load are associated with survival in naturally infected cats. Viruses 2021;13(2):302.
Gomes‐Keller MA, Tandon R, Gonczi E et al. Shedding of feline leukemia virus RNA in saliva is a consistent feature in viremic cats. Vet Microbiol 2006;112(1):11–21.
Beall MJ, Buch J, Cahill RJ et al. Evaluation of a quantitative enzyme‐linked immunosorbent assay for feline leukemia virus p27 antigen and comparison to proviral DNA loads by real‐time polymerase chain reaction. Comp Immunol Microbiol Infect Dis 2019;67:101348.
Saag MS, Holodniy M, Kuritzkes DR et al. HIV viral load markers in clinical practice. Nat Med 1996;2(6):625–629.
World Health Organization. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. 2021.
Yeni PG, Hammer SM, Carpenter CC et al. Antiretroviral treatment for adult HIV infection in 2002: updated recommendations of the international AIDS society‐USA panel. JAMA 2002;288(2):222–235.
Little S, Levy J, Hartmann K et al. 2020 AAFP feline retrovirus testing and management guidelines. J Feline Med Surg 2020;22(1):5–30.
Jitta SR, Bhaskaran NA, Marques SM, Kumar L. Recent advances in nanoformulation development of ritonavir, a key protease inhibitor used in the treatment of HIV‐AIDS. Expert Opin Drug Deliv 2022;19(9):1133–1148.
Centre for Health Protection. Recommended principles of antiretroviral therapy in HIV disease. 2011.
Helfer‐Hungerbuehler AK, Shah J, Meili T et al. Adeno‐associated vector‐delivered CRISPR/SaCas9 system reduces feline leukemia virus production in vitro. Viruses 2021;13(8):1636.
Chiu ES, Hoover EA, VandeWoude S. A retrospective examination of feline leukemia subgroup characterization: viral interference assays to deep sequencing. Viruses 2018;10:1.