Last week, I wrote about the use of oseltamivir in dogs and cats infected with H5N1 influenza. We have to be aware of the risk of drug resistance risks whenever we use anti-infectives, especially when the same drugs (like osteltamivir) are used in people, and assess the risks and benefits in order to “use as little as possible, but use enough.”

That’s lead to some questions about use of the antiviral GS-441524 in cats. This drug has been a game changer in the management of a previously almost invariably fatal disease in cats called feline infectious peritonitis (FIP). 

When considering use of oseltamivir for treatment of H5N1 flu, there are a few things to our advantage:

• It’s a narrow spectrum antiviral 
• H5N1 infection and virus shedding are short term 
• There’s no endemic H5N1 flu virus circulating in the cat and dog population
• Cats and dogs are not common (if ever) sources of H5N1 transmission to people
• We can implement infection control measures during the short treatment course required and estimated virus shedding period to contain the risk of spread of any resistant virus

The risk of a resistant H5N1 virus emerging during use of osteltamivir in a pet is therefore low, and the risk of any such virus spreading is even lower. While there’s some risk, with basic precautions, I think we can justify its use in infected pets under the right circumstances.

When considering use of GS-441524 (GS) for treatment of FIP, there are some very important differences:

• GS is a broader spectrum antiviral
• Enteric feline coronavirus (the virus that mutates to ultimately cause FIP in cats) can be shed by infected cats for months
• Enteric feline coronavirus is a cat-adapted virus that can spreads very efficiently from cat-to-cat via fecal-oraltransmission

The risks of resistance when using GS in cats therefore differ according to the scenario.

1. Using GS to treat a cat with FIP

• There’s a risk of emergence of resistant FIP virus within a treated cat. This would be bad news for the cat, but probably of limited broader risk since once enteric feline coronavirus becomes a cause of FIP, it’s not readily transmitted anymore. Odds are that the cat would not transmit the resistant virus further. We can’t say there’s no risk, but it’s low risk.
• If the cat had concurrent intestinal infection with feline coronavirus, then there would be a risk of that virus becoming resistant and then spreading. One study reported fecal shedding of feline coronavirus in 61% of cats with FIP that were being treated with GS . Shedding dropped fairly quickly in most cats, which shows some likely impact of the drug, but it also shows that there’s some plausible risk of resistance emergence and transmission.
• Since FIP is devastating, GS is highly effective, and the risk of resistance spreading is low, this is clearly a high-benefit / low-risk use situation. However, it’s not no risk so we need to study it more and optimize our treatment approaches.

2. Using GS to treat cat with enteric feline coronavirus infection

• Feline coronavirus is widespread and continually circulating in cats. There’s been some discussion of use of GS to knock that back, and to try to eliminate it from groups of cats (e.g. catteries). Treatment will reduce fecal shedding of the virus, and less shedding would likely have some downstream reduction of FIP, but I have my doubts that we can do much to control spread in the grand scheme with an antiviral. Reducing and eliminating a virus are different, and reducing while creating a substantial risk of resistance isn’t usually a good combination. In general, we are rarely able to use anti-infective drugs for effective infection control approaches in a population, especially for a virus that’s host adapted and endemic.
• If we are treating cats with enteric infection, there’s a lot of virus, a lot of cats and a lot of chance for resistance emergence. If resistance emerged in a cat, it could shed large amounts of virus for long periods of time, releasing GS-resistant virus into the cat population and hampering our ability to treat FIP when it occurs. That’s a big concern for me.
• Since enteric feline coronavirus infection isn’t a major health issue, treatment is not likely to have a major impact on enteric virus circulation, GS is so important for cats with FIP, and resistance would result in cat deaths, I have a hard time finding an indication for use of GS for enteric feline coronavirus.

Dr. Niels Pedersen, a (or The) leader in development of antiviral approaches for FIP has a nice commentary entitled “Inappropriate use of GS-441524 in an attempt to eliminate Feline Enteric Coronavirus (FECV) from healthy cats.” The title gives away his thoughts on the matter. It’s a good, impassioned summary of why we need to be good stewards of FIP antivirals and why targeting feline enteric coronavirus is likely a bad idea.