Alpha interferon (2b) in combination with zidovudine for the treatment of presymptomatic feline leukemia virus-induced immunodeficiency syndrome

Abstract

The therapeutic efficacies of human recombinant alpha interferon (IFN-alpha), IFN-alpha plus zidovudine (AZT), and AZT alone were evaluated in presymptomatic cats with established feline leukemia virus (FeLV)-acquired immunodeficiency syndrome (FAIDS) infection and high levels of persistent antigenemia. Subcutaneous injection of 1.6 x 10(6) U of human recombinant IFN-alpha 2b per kg delivered peak concentrations in plasma of 3,600 U/ml at 2 h postadministration with a half-life of elimination of 2.9 h. This dosage of IFN-alpha could be delivered to cats for up to 12 weeks without significant clinical toxicity. Oral administration of AZT (20 mg/kg three times daily) resulted in peak concentrations in plasma of 3 micrograms/ml at 2 h with a half-life of elimination of approximately 1.60 h. Treatment of FeLV-FAIDS-infected cats with IFN-alpha, either alone or in combination with orally administered AZT, resulted in significant decreases in circulating p27 core antigen beginning 2 weeks after the initiation of therapy. AZT alone had no effect on circulating virus antigen. Depending upon whether high (1.6 x 10(6) U/kg)- or low (1.6 x 10(4) to 1.6 x 10(5) U/kg)-dosage IFN-alpha was used, cats became refractory to therapy 3 or 7 weeks after the beginning of treatment. At these times, IFN-alpha-treated animals developed antibodies to IFN-alpha that were neutralizing, specific for human recombinant IFN-alpha, and dose dependent in magnitude. The results of this study indicate that human recombinant IFN-alpha is effective in reducing circulating virus antigenic load in cats persistently infected with FeLV-FAIDS. However, the continued efficacy of IFN-alpha therapy appeared to be limited by the formation of cytokine-specific neutralizing antibodies.

Therapeutic Effects of Recombinant Feline Interferon‐co on Feline Leukemia Virus (FeLV)‐Infected and FeLV/Feline Immunodeficiency Virus (FIV)‐Coinfected Symptomatic Cats

“…Regarding the use of IFNs in FeLV-and FIV-associated diseases, some studies showed encouraging and sometimes dramatic therapeutic effects on symptomatic as well as asymptomatic cats, [11][12][13][14][15] whereas other more recent studies failed to confirm previous observations. 16,17 The discrepancies may be attributed, at least in part, to different study designs, notably regarding (sub)types of IFN, species of origin, purity of preparations, treatment route, dosage, and schedule, as well as the age and pathological stage of FeLVinfected cats.…”

Efficacy of antiviral chemotherapy for retrovirus-infected cats

“…116 One study evaluated the therapeutic efficacy of high dose IFN-α (1.6 x 10 4 to 1.6 x 10 6 IU/kg SC q24h) in experimentally FeLV-infected cats with persistently high levels of antigenaemia. 46 Treatment resulted in a significant decrease in circulating FeLV antigen beginning 2 weeks after the initiation of therapy (EBM grade II). 46 However, because of anti-IFN-α antibody development, cats became refractory to therapy 3 or 7 weeks after starting treatment.…”

“…46 Treatment resulted in a significant decrease in circulating FeLV antigen beginning 2 weeks after the initiation of therapy (EBM grade II). 46 However, because of anti-IFN-α antibody development, cats became refractory to therapy 3 or 7 weeks after starting treatment. 46 In a placebo-controlled, doubleblind study in naturally FeLV-infected cats using a similar high dose regimen, treatment with IFN-α (1 x 10 5 IU/kg SC q24h for 6 weeks) did not lead to a significant improvement in clinical, laboratory, immuno logical or virological parameters (EBM grade I).…”

“…When treated less than 1 week after challenge, cats were protected from bone marrow infection and persistent viraemia (EBM grade II). 45,46 In a study in which cats naturally infected with FeLV were treated with zidovudine for 6 weeks, however, treatment did not lead to a significant improvement in clinical, laboratory, immunological or virological parameters (EBM grade I). 47 Thus, overall therapeutic efficacy of zidovudine is less promising in FeLV-infected cats than in FIV-infected cats.…”

“…When given parenterally to cats, human iFN-α becomes ineffective after 3-7 weeks due to the development of neutralising antibodies that limit its activity. 46 IFN-α can be given orally for a longer period as no antibodies will develop during oral treatment, and it has been used in this manner to treat FIV and FeLV infections. However, given orally, IFN-α is inactivated by gastric acid and destroyed by trypsin and other proteolytic enzymes in the duodenum.…”