Antiviral treatment of feline immunodeficiency virus-infected cats with (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine

Abstract

Feline immunodeficiency virus (FIV), the causative agent of an acquired immunodeficiency syndrome in cats (feline AIDS), is a ubiquitous health threat to the domestic and feral cat population, also triggering disease in wild animals. No registered antiviral compounds are currently available to treat FIV-infected cats. Several human antiviral drugs have been used experimentally in cats, but not without the development of serious adverse effects. Here we report on the treatment of six naturally FIV-infected cats, suffering from moderate to severe disease, with the antiretroviral compound (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine ([R]-PMPDAP), a close analogue of tenofovir, a widely prescribed anti-HIV drug in human medicine. An improvement in the average Karnofsky score (pretreatment 33.2 ± 9.4%, post-treatment 65±12.3%), some laboratory parameters (ie, serum amyloid A and gammaglobulins) and a decrease of FIV viral load in plasma were noted in most cats. The role of concurrent medication in ameliorating the Karnofsky score, as well as the possible development of haematological side effects, are discussed. Side effects, when noted, appeared mild and reversible upon cessation of treatment. Although strong conclusions cannot be drawn owing to the small number of patients and lack of a placebo-treated control group, the activity of (R)-PMPDAP, as observed here, warrants further investigation.

Serum and urinary cystatin C in cats with feline immunodeficiency virus infection and cats with hyperthyroidism

“…In particular, male neutered cats were overrepresented in the FIV-infected group, which is similar to other reports. [55][56][57] However, no effect of age or sex on sCysC could be observed in a recent study by our group. The effect of age and sex on uCysC has not yet been evaluated.…”

Feline Immunodeficiency Virus Neuropathogenesis: A Model for HIV-Induced CNS Inflammation and Neurodegeneration

“…Among the many achievements, these efforts led to approval of an effective FIV vaccine in 2002. Recent studies have addressed important issues such as mechanisms of FIV transmission, replication and evolution [ 22 , 23 , 24 , 25 , 26 , 27 ], FIV vaccine efficacy [ 28 , 29 ], the role of neutralizing antibodies in disease progression [ 28 , 30 , 31 ], virus assembly and release [ 32 , 33 ], viral latency and eradication strategies [ 34 , 35 , 36 ], development of adjunctive therapies [ 37 , 38 , 39 , 40 ], immunology [ 41 , 42 , 43 , 44 , 45 ], interactions with the microbiome [ 46 , 47 ], development of antiretroviral compounds [ 48 , 49 , 50 ] and development of protocols for assessing feline cognitive function [ 51 , 52 , 53 , 54 ]. Many of these efforts are summarized in this volume and in a review by Bienzle [ 55 ].…”

Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects

“…It is also strongly active against animal retroviruses, especially feline immunodeficiency virus. Although strong conclusions cannot still be done, some studies revealed slightly positive ( Vahlenkamp et al, 1995 ; Taffin et al, 2015 ). It is clear that the activity of ( R )-PMPDAP in vivo warrants further investigations including synthesis of prodrugs ( Krečmerová et al, 2013 ).…”