Use of two virustatica (AZT, PMEA) in the treatment of FIV and of FeLV seropositive cats with clinical symptoms

Abstract

In the present study the therapeutic efficacy and the side effects of two antiretroviral compounds used in human acquired immunodeficiency syndrome (AIDS) research, 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine, Retrovir) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA), were investigated in the treatment of cats naturally infected with feline immunodeficiency virus (FIV) and cats naturally infected with feline leukemia virus (FeLV). AZT was administered subcutaneously at a dose of 5 mg kg-1 body weight every 12 h and PMEA was administered subcutaneously at a dose of 2.5 mg kg-1 body weight every 12 h during a 3 week hospitalization. The therapeutic efficacy of both compounds was investigated. There was a stronger potency of PMEA than of AZT on the regression of stomatitis in FIV and in FeLV infected cats. In addition, in FIV infection PMEA had a stronger effect on the improvement of the general clinical status. Both antiretroviral compounds were potent agents to improve the immunologic status of FIV infected cats by raising the CD4/CD8 ratio. In FeLV infection PMEA and AZT appeared to reduce antigenemia. The hematological side effects caused by PMEA were severe and stronger than those of AZT. Therefore the advantage of PMEA in clinical and immunologic improvement was diminished by the hematologic disorders, which do not allow long term treatment with this drug in the dose used.

Efficacy of antiviral chemotherapy for retrovirus-infected cats

“…62 Several studies have investigated the efficacy of adefovir in cats either experimentally or naturally infected with FIV. 10,[63][64][65][66][67] Some of these studies have reported some efficacy, but also severe side effects, mainly in the form of non-regenerative anaemia. More recently, adefovir was used in FIV-infected cats in a 6 week placebo-controlled, double-blind clinical trial; 10 cats received the drug (10 mg/kg SC twice weekly) and 10 cats received placebo.…”

A trial with 3′-azido-2′,3′-dideoxythymidine and human interferon-α in cats naturally infected with feline leukaemia virus

“…When given alone in other studies, AZT was also not very effective in experimentally-or naturally-infected cats. 11,13,16 Only when given prophylactically (before experimental infection), AZT had some effect and could prevent development of persistent viraemia. 16,17 Although it was not to be expected that AZT alone would have a notable effect in naturally-infected FeLV cats, the combination of AZT and IFN-α2a was considered a promising approach.…”

“…Severe anaemia develops during treatment of cats infected naturally with FeLV at AZT dosages of 10 mg/kg. 11 Thus, a rather cautious approach was chosen in the present study. The huIFNα2a dosage of 10 5 IU/kg q24h used in the present study equates to the middle dosage used in one of the studies by Zeidner et al 13 and was chosen in the present study because a higher dosage in cats would be expected to stimulate development of neutralising antibodies against the heterologous interferon within 3 weeks.…”

“…10 Cats infected naturally with FeLV and treated with AZT for 3 weeks had significant improvement in their stomatitis. 11 The combination of 'high-dose' huIFN-α and AZT seemed to be particularly promising. In a placebocontrolled study, prophylactic treatment of cats infected experimentally with FeLV using a combination of AZT and huIFN-α2a prevented development of persistent viraemia.…”

Comparative Anti-Retrovirus and Anti-Hepadnavirus Activity of Three Different Classes of Nucleoside Phosphonate Derivatives

“…PMEA also proved effective in inhibiting Moloney murine sarcoma virus (MSV)-induced transformation of murine C3H/3T3 embryo fibroblast cells at 1 J..lM, feline immunodeficiency virus (FIV) replication in Crandell feline kidney cells and in feline peripheral blood lymphocytes at 0.3-1.3 and 0.06-0.1 J..lM, respectively, and simian immunodeficiency virus (SIV)-induced giant cell formation and cytopathic effect in HUT-78 and MT-4 cells at 4-17 J..lM (Balzarini et al, 1989(Balzarini et al, , 1991Egberink et al, 1990;Hartmann et sl., 1993Hartmann et sl., , 1994. Moreover, PMEA showed potent and selective anti-retrovirus activity in several animal models including MSV infection in newborn NMRI mice (Balzarini et al, 1989(Balzarini et al, , 1991, FIV infection in cats (Hartmann et al, 1993) and SIV infection in rhesus monkeys (Egberink et al, 1990;Tsai et al, 1994). Interestingly, PMEA has also shown activity against human and duck hepatitis B virus in human HB611 and Hep G2 2.2.15 cells and in primary duck hepatocyte cultures at 0.2 and 1.2 J..lM, respectively (Heijtink et al, 1993;Yokota et al, 1994).…”