• 24 Mar 2022
  • 33min 37
  • 24 Mar 2022
  • 33min 37

In this episode, NPS MedicineWise medical advisor Dr Caroline West speaks with Prof Sarah Hilmer and Prof Josh Davis, members of the National COVID-19 Clinical Evidence Taskforce Guidelines Leadership Group. They give an update on the new antiviral treatments now available and answer some frequently asked COVID management questions.

Further reading

NPS MedicineWise www.nps.org.au/coronavirus/faqs-covid-19-antivirals-in-racfs

National COVID-19 Clinical Evidence Taskforce www.covid19evidence.net.au

Liverpool University Drug Interaction www.hiv-druginteractions.org/checker

Transcript

Dr. Caroline West:
Hello and welcome. I'm Dr. Caroline West, a medical advisor to NPS MedicineWise, and a GP. Now, COVID is providing us with plenty of challenges, especially with new variants emerging. The latest Omicron variant BA.2 is possibly 30 to 40% more transmissible than the previously dominant BA.1. At NPS MedicineWise, we've been providing resources and podcasts around COVID to keep you well informed. Managing COVID is of course a fast-moving field. and just in the last few weeks, since our recent podcast, things have continued to evolve. So we are keen to do part two today of an update on treatments. There are two new oral COVID antivirals molnupiravir, and the combination Paxlovid, which is nirmatrelvir and ritonavir, but there are a range of other treatments too that may be offered. To take us through an update with frequently asked COVID management questions, I'm joined by two experts who are on the National COVID-19 Evidence Taskforce and who are part of the Guideline Leadership Group. Professor Josh Davis is an infectious diseases physician and a clinical researcher at the John Hunter Hospital in Newcastle, New South Wales; Professor Sarah Hilmer is a geriatrician and clinical pharmacologist . Welcome to you both.

Professor Josh Davis:
Hi, Caroline.

Dr. Caroline West:
Now, so much has been changing rapidly. I thought maybe we could start off by just getting a snapshot of where we're up to with BA.2. What are we up against here? Sarah.

Professor Sarah Hilmer:
BA.2 as we've seen on the front page of the newspaper is a more infectious variant. And at this stage, it seems like it accounts for about 25% of the new cases in New South Wales. And looking at overseas data that's likely to increase. We don't know if it's more or less virulent than the other variants. And I guess time will tell. One of the things that is really important for us to understand as prescribers when we think about BA.2, is that it might affect how different medicines for COVID-19 work and might be resistant to some of the drugs that we've previously used on previous variants.

Dr. Caroline West:
And so Josh, do you think this is something we need to prepare ourselves for is just continuing, emerging variants around the world that are going to surprise us?

Professor Josh Davis:
Yeah, well, hopefully they won't surprise us because we'll be expecting them. But I mean, people suggested early on a couple of years ago that this was going to happen because coronaviruses are very error prone when they replicate, meaning mutations happen. And if those mutations get selected for then you're going to have variants like this emerge. And so it's not a surprise that it started to happen. It will continue to happen. Luckily, Omicron and BA.2 as well are way less virulent than earlier variants and causing much less severe disease, even though they're more contagious. So it is going to continue to happen. It may affect the efficacy of the drugs that we've got.

Dr. Caroline West:
And I know that clinicians and patients have been very interested in the new COVID treatments that have arrived in Australia. I wonder if I can go back to you, Sarah, can we start with a bit of a refresher perhaps on the oral antivirals available in Australia and how they work?

Professor Sarah Hilmer:
There are two oral antiviral available in Australia. One is molnupiravir. This one basically causes the virus to mutate and actually mutate to the extent that it dies. So in a more technical way, we would say that it's taken up by the viral RNA-dependent RNA polymerases and causes lethal mutagenesis. The other drug that we have is a combination drug. It's nirmatrelvir plus ritonavir. Nirmatrelvir is a new antiviral and it actually stops the virus from replicating. The ritonavir is there really to stop the metabolism of the nirmatrelvir so it's at a level that it can do its job. And in a more technical way, the nirmatrelvir inhibits the SARS-CoV-2 main protease and the ritonavir inhibits the cytochrome P4503A4.

Dr. Caroline West:
So the ritonavir, some people may be familiar with that component of that combo drug because it's been used in the past in HIV. So basically what you're saying is that helps boost the effectiveness of the nirmatrelvir?

Professor Sarah Hilmer:
Exactly. It allows the nirmatrelvir to be at a level in your blood that it can work. It stops it from being metabolized quickly by the liver.

Dr. Caroline West:
Great. Okay. We'll come back to that in a moment with perhaps how that's going to affect things like side effects and interactions. But if I can come back to you, Josh, how effective are these oral antivirals? What do we know so far?

Professor Josh Davis:
Yeah, so I guess a couple of caveats before we get into the data is that nearly all the information we've got on efficacy comes from a single large randomized trial conducted by the drug company for each of these two drugs. And when these trials were done, it was really at a time when Delta was circulating or prior to Delta. So in other words, there's no patients with Omicron in these trials. And then also patients who were vaccinated or partially vaccinated were excluded from the trials. So a lot of the people we’re using these or recommending the drugs for now it's uncertain exactly the efficacy. But having said all that stuff, the bottom line is Paxlovid works a lot better than molnupiravir from the data that we have. It reduces the risk of either hospital admission or death by 70 to 90%. And molnupiravir reduces that risk by about 30% based on the clinical trial data.

Dr. Caroline West:
So if there's such a difference in efficacy, what are the criteria that we'd apply then if we are trying to decide whether somebody should be placed on either one?

Professor Josh Davis:
Well, it's down to availability and drug interactions and contraindications. So Paxlovid has a lot of drug interactions, maybe Sarah will talk about that in a minute, mainly because of the ritonavir. So people that are already taking certain medications, they can't have Paxlovid. Both of them are not safe in pregnancy. But really it'll come down to availability. At the moment, molnupiravir is a lot easier for GPs to prescribe because it's on the PBS. Paxlovid can be prescribed by GPs under systems that have been set up in the different states from the National Medical Stockpile. My personal view is that if Paxlovid is not contraindicated and you can get it, it's always preferable. And that's what the National COVID Evidence Taskforce's recommendations also say.

Dr. Caroline West:
I know that when you look at the Paxlovid data and you look at the interactions, there's a huge number of things to consider as a clinician. Sarah, just back to you, as you've mentioned, is that an effect of the ritonovir that we are seeing that produces all of these side effects or drug interactions, which there are so many drugs that interact with it. It's kind of a bit overwhelming when you look at the long list.

Professor Sarah Hilmer:
I think that's right. And I think that's why people have been cautious in starting patients on nirmatrelvir plus ritonavir. However, I think if people understand the basis for the interactions, they will realize that most of them are in fact manageable and it's worth just taking your time to work through them with your patient to see if your patient is in fact able to tolerate nirmatrelvir plus ritonavir. I think it's worth just thinking about sort of how these actions arise, because most of the time there might be an interaction, but actually it's a manageable interaction. And if you have enough time, you can still give the patient the drug, which is likely to be more effective than the alternative.

Dr. Caroline West:
So what you're saying is it's not an absolute, just because there's an interaction that wouldn't be seen as necessarily a contraindication?

Professor Sarah Hilmer:
Not necessarily, there are some situations where it is and there are others where it's not, and that's where it really helps to understand how these interactions arise. And so there are some interactions where the ritonavir component blocks cytochrome P4503A4, and that results in increase in concentration of the cytochrome P4503A4 substrates. So that happens almost straightaway. It happens within days, if you're blocking an enzyme, it happens fast. So when you look at the advice around different CYP3A4 substrates with narrow therapeutic indices, often you have to stop and wash that drug out for a couple of half lives before you start the Paxlovid. The other type interactions that we think about are the ones where a person was already on a CYP3A4 inducer. So their CYP3A4 is already so induced that they'll wind up with the spike of ritonavir with a low concentration of the nirmatrelvir. And it won't be effective and just breed resistance. And those ones are actually a little bit trickier because the induction time really takes weeks to occur. But once it's occurred, it takes weeks to wear off because you've actually got to wait till that enzyme that's already been induced dissipates. So those are the ones where the timeframe doesn't really fit with your five days.

Dr. Caroline West:
So both of these oral antivirals need to be given in the first five days of symptoms. Josh, if I can turn to you, I guess that for new prescribers of this medication, it's like when you start prescribing anything, you often have to get a sense of confidence in doing so and know where to look for the information. So as a GP, what's the best way to tackle that if you've got somebody who's on the phone, who's in a higher risk group, perhaps they've got a text message after they've recorded their RAT test saying, "Look, you could be a suitable candidate for treatment." What are the practical next steps that happen?

Professor Josh Davis:
I think the best place to look is the National COVID Evidence Taskforce website that you alluded to before, it's covid19evidence.net.au. It has flow charts on it that are designed for use at the point of care, where you can sort of look where your patient fits into the flow chart. And therefore whether a drug would be recommended or not, and they're updated potentially every week or the evidence is updated every week. Each state health department also has its own resources directed at GPs and other prescribers as well. So you might want to go to one of their websites. There are a lot of other resources too, such as from NPS MedicineWise, but the most up-to-date one will be the COVID Evidence Taskforce website, and then there's HealthPathways we mentioned earlier. So that's a lot of information, but if a GP is not confident to prescribe, doesn't really know, I'd go straight to the website and look at the flow chart for their patient.

Dr. Caroline West:
And I guess that there's some confusion from some of the GPs I've spoken to about what they can prescribe. So molnupiravir is now PBS listed. So some GPs have assumed, "Oh, well, that's the one I should be prescribing." And they're not that confident or aware of the pathway to get Paxlovid if they feel that would've been a better choice. But basically for a GP, even though both are provisionally, registered, and both are available, is that the current state of play?

Professor Sarah Hilmer:
Yes. It’s just a matter of working out what the access pathway is in your state for the nirmatrelvir plus ritonavir.

Professor Josh Davis:
Yeah. It's important for GPs not to assume that because molnupiravir is PBS listed and Paxlovid isn't that that means that the panel thought molnupiravir is better. It's not that. It's to do with negotiations happening behind the scene about funding and government deals and all that kind of stuff. It's just Paxlovid will become PBS funded at some point. It just hasn't got through all the systems yet.

Dr. Caroline West:
And in terms of the questions that you are going through with clinicians and with patients, are people, especially in the broader community, what's the messaging around that it doesn't replace vaccination? Is there some confusion there? Because some people have said to me, "Oh, look, I'm not going to get vaccinated because I could just get a treatment." Are you hearing that? And what would your response be to somebody who has that thinking? Josh.

Professor Josh Davis:
Yes. I mean, I have heard that from patients that are vaccine hesitant, who end up in hospital with COVID. A lot of them say, "Oh, actually I'll have the vaccine now. Thanks." So sorry, it's too late. You've got COVID. I mean, yes, you should probably be vaccinated later on, so yeah, I agree there is some misinformation or maybe even wishful thinking out there in the public that these things will be a safety net for those that are unvaccinated. And that's not the case, it's much better obviously to prevent than to treat COVID. And these drugs are not a 100% effective. Like I said, they reduce your risk of hospitalization or death, but they don't take it away. And vaccination is much more potent at reducing your risk than any of these medications are.

Professor Sarah Hilmer:
It's also worth pointing out that there's a lot more data on vaccination in terms of safety, that they've been used in tens of thousands, hundreds of thousands, millions of people. Well, the data we have on these drugs has been in trials of 1000 people. So we have no idea what the rare side effects of these drugs are.

Dr. Caroline West:
It's such an interesting time in medicine, isn't it? Because normally for a drug to even be provisionally registered there's quite a long timeline, and we've seen these medications due to the urgency of COVID being moved along when, as you say, there's not a tremendous amount of data yet in terms of understanding how they'll fit in the picture.

Professor Sarah Hilmer:
Yeah, I think that's right. And I think that's why it's really important that if we do note adverse effects for these drugs, that we report them, because with the trial sizes we have in the ballpark of 1000 to 2000 people, we are just not going to be powered to see rare side effects, pretty much anything that occurs in sort of at a rate of less than 5% we're not powered to see. So we're only going to learn about those rare side effects when we use the drugs and we report anything that looks like an adverse event.

Dr. Caroline West:
I guess if we are moving towards a model where we are managing many people at home in the community, these medications are welcome, adjunct to the toolbox because they allow us to perhaps offset the risk of going to hospital with more severe disease.

Professor Josh Davis:
Caroline, I might jump in there and just address another thing that people are confused about or that there's conflicting information out there about. The majority of people who have COVID don't need any of these medications and can be managed safely at home with just ibuprofen, paracetamol, whatever symptom treatment. One of these medications, either molnupiravir or the nirmatrelvir to be recommended, or sotrovimab indeed, there has to be five criteria that you meet that the patient meets. So one is, it's early disease, less than five days from symptom onset that we've already talked about. Second is, it has to be symptomatic disease. So it's not just asymptomatic positive RAT test or something. Third is, they have to have risk factors for severe disease. And that's the most important one. Those are mostly based on age, such as over 60, for example, but also things like diabetes. So that's three. Fourth one is, they're not sick enough to be in hospital on oxygen. So it's early disease. And finally, they have to have reduced immunity, meaning either they're not vaccinated or they're immunosuppressed or they're overdue for vaccination. So reduced immunity early in disease and risk factors. So if they don't have all of those things, it's not indicated to give them the drugs.

Dr. Caroline West:
And if they were unfortunate enough to become very unwell, because occasionally you do see outliers who don't fit the clinical criteria for risk and end up in hospital. There are other medications that may be offered further down the track with the condition. Maybe this is a good time to just touch base on what are we commonly using if somebody goes to hospital and what's a timeframe for that.

Professor Josh Davis:
Yeah, sure. So if people are hospitalized because of being sick with COVID-19, and I'm using those words a bit carefully now, because a lot of the hospital admissions we're seeing now in the Omicron era are with COVID-19, not because of COVID-19. In other words, the patient's got an exacerbation of their heart failure or they've got a broken leg or something like that. And they happen to have COVID as well. But if COVID is really driving the admission, so they've got pneumonitis, let's say, then most patients will be given remdesivir intravenously, which is another antiviral drug. If they're needing oxygen, they'll be given dexamethasone corticosteroid to reduce the lung inflammation. And if despite those two things they're quite sick and escalating oxygen requirements, they'll be given baricitinib to block the inflammatory pathways and decrease their risk of severe pneumonitis and ICU admission.

Dr. Caroline West:
Sotrovimab is one of the treatments that sometimes offered in a hospital setting. If we can talk about that for a moment, because splashed across the news this week has been the whole question of resistance and what we're seeing there and the implications for this in terms of managing COVID. Sarah, just back to you for a moment, what should we make of this?

Professor Sarah Hilmer:
The first thing I want to make very clear Caroline is that sotrovimab has the same place in therapy as the oral antivirals. It's for early disease. Exactly the same criteria that Josh just described. While we administer it often in hospital, because that's where we can give an intravenous infusion. It's actually for people who are not sick enough from COVID to need to be in hospital. In terms of its potential role in BA.2, there are, I guess, conflicting data at the moment. On one hand, there are some laboratory studies that suggest that BA.2 is probably quite resistant to sotrovimab. And if they turn out to be proven to be correct in real world settings, then I think that's going to mean that we really do need to start using these oral antivirals a whole lot more. There is other data which hasn't yet been published, which might suggest that's not true. But at this stage there is certainly doubt about whether sotrovimab is going to work nearly as well in BA.2. And I think that is a really good reason to start familiarizing ourselves with the oral antivirals, because at this stage it seems the BA.2 should be susceptible to the oral antivirals to the same extent as some of the earlier strains.

Dr. Caroline West:
And we've talked about some of the considerations in terms of drug interactions with the oral antivirals. What about if you have somebody who's in that age group where they may become pregnant or they're already pregnant or they're thinking about conception?

Professor Sarah Hilmer:
Look, with both of them, you don't want to give them to someone who is pregnant. They both have been associated in animal studies with injury to the fetus and spontaneous abortion. So you certainly don't want to give either of them to a pregnant person. You particularly don't want to give molnupiravir because it drives mutations. You can imagine that's not going to be good for developing fetus. So for women we say ”Make sure you're not pregnant before you take them and take contraception while you're taking them and for a few days afterwards”. The story gets actually more complicated for men with the molnupiravir, because the molnupiravir can actually cause mutations to the sperm. And so any sperm that are there at the time you're taking it could potentially be affected. And that's why for men, when they take molnupiravir, we say, do not conceive, use appropriate contraception for after three months after you finished the molnupiravir, because otherwise your child could be affected. So you shouldn't take while your pregnant. And for men with molnupiravir, you shouldn't conceive for three months after you've taken them.

Dr. Caroline West:
And in terms of the questions that patients consumers may have about these medications, Josh, have you been fielding questions from people about what they should do and are you observing that people are becoming more interested in COVID and sort of, I guess, asking more questions are around what having COVID means and what the options are?

Professor Josh Davis:
Yes and no, actually. So what I mean by that is, absolutely yes a few months ago. Absolutely yes during the Delta peak, but lately people seem to be losing interest a bit because it's causing much less severe disease, far fewer hospitalizations, far fewer deaths. And we're learning to live with the virus and inverted commerce. People have become a bit more lackadaisical about it and less interested. But yeah, we still when we're on call for infectious diseases, we still are getting calls from all around. Lots of GPs, lots of hospital doctors. Should I give this patient sotrovimab? Should I give them molnupiravir? Et cetera. So yeah, so a lot of questions, but I think less interest than there was.

Professor Sarah Hilmer:
I think I'm getting questions particularly from, I guess, the older, co-morbid population. Firstly, wanting to know, what should I have if I get sick? What should I do if I get sick? They're aware that there is something that they can do. And I think one of the main things you can say to people is talk to your doctor straight away, you would be eligible for treatment. There are also people who are asking, can you look at my medicine? Is there something that might interact with the ritonovir? Should I change some my chronic medicines in case I need it? I think that's probably overkill as a rule. There are other options, but those are the sorts of questions that I'm getting.

Dr. Caroline West:
And being a geriatrician, I guess there's been a lot of interest and there's been pre-placement of molnupiravir in aged care facilities. I have talked to some doctors who have been a little unclear about whether that means that's their first go-to or whether they should go down the pathway of Paxlovid, as you said, exploring the interaction option a little further, have you got any comments on that?

Professor Sarah Hilmer:
I think it's important to recognize that yeah, people living in residential aged care can access exactly the same care as people who are not living in residential aged care. And if a person in residential aged care can tolerate the nirmatrelvir, ritonavir, then you should give that to them as their first option. You need to worry about interactions. And a lot of people in aged care are taking a lot of medicines and will have interactions. But at the same time, often you'll catch it pretty early in aged care because it's an outbreak and you're screening everybody. And so you may well have time to deal with those interactions. The other key things you need to think about with the nirmatrelvir, ritonavir is renal impairment. So if people have an eGFR between 30 and 60, you need to dose reduce. That's fine. You can do that. But if their eGFR is less than 30, which actually is a large proportion of people in residential age care, then they can't take the drug. And that's because once you block the hepatic metabolism of the nirmatrelvir, it only has one way out and that's through the kidneys. And so if a person's kidneys aren't working at all, then they can't clear the nirmatrelvir well enough and they can't have it, because we just don't know what sort of side effects they'll get with a very high level. So you should certainly think about giving your people in residential aged care, nirmatrelvir ritonavir, but you do need to think not only about the interactions, but also about their renal function.

Dr. Caroline West:
it's good to clarify that. So Josh, are you finding that you are sort of working through those issues of renal function when you're assessing patients?

Professor Josh Davis:
Yeah. I mean, look, I don't generally assess the patients myself. It's mainly happening in general practice or at peripheral hospitals. Occasionally we get a patient where we have to make the decision in real time, but usually it's already happened. And a good example of maybe a cautionary tale that happened last week. One of the patients was on our COVID care in the home team, so like hospital and the home type situation, and their GP had started them on Paxlovid and referred them in for ongoing monitoring. And they rang the COVID care in the home nurses and said, "I just feel really bad." It was day four, I think, of their COVID.
"I just feel like fainting every time I stand up." So as it turned out, that patient was on lercanidipine for their blood pressure, started Paxlovid that's a known drug interaction which the prescriber had sort of missed and got that explained that they had quite bad posture hypotension, and it all got better when we stopped the Paxlovid. But I didn't really answer your question there, but I think that's an interesting little story.

Dr. Caroline West:
Yeah. I think there'll be lots of those stories coming through as there are little surprises in terms of those combinations and the effects that it has on people.

Professor Josh Davis:
But yeah, actually I might just use that to do a little plug for the Liverpool University Drug Interaction website. So Liverpool University in the UK have for years been doing this for other antiviral, Hep C and HIV drug that I use a lot, but they have a website and app that has good up-to-date information. So you can type in the drugs that the patient's on, the drug you want to put them on, Paxlovid or molnupiravir or whatever, and it will tell you about interactions and the nature of them and how to deal with them.

Dr. Caroline West:
Fantastic.

Professor Sarah Hilmer:
And I will just make it additional plug to say, it's a fantastic website, but in order to use it effectively, you have to know what the person's on. And so it's really important when you're doing assessment to just make sure you know what over the counter complementary alternative medicines, other things the person might be taking, because there are interactions with all sorts of things you might not expect, like say St. John's ward.

Dr. Caroline West:
I always find it hard with all of those supplements that people are on, sometimes even knowing what's in them.

Professor Sarah Hilmer:
I think you've just got to ask and I guess a lot of the times is done over the phone, which makes it a bit tricky because the person's doing a tele consultation, but yeah, just get them to spell out exactly what they're taking and if you need to look it up, look it up because you'll get some surprises and you don't want to poison your patient.

Dr. Caroline West:
Yeah. And what does the future look like? I know that all of us have the crystal ball out all the time with COVID and we're never right or not very often, what do you think will happen in this space of management? What's the next six to 12 months going to look like, do you think? What are your predictions there? Will we see more antivirals coming on?

Professor Josh Davis:
I mean, there are more antivirals in development. The concern about antiviral resistance has meant that companies are looking into combination therapy and developing single pill combination therapies for a drug that might block both the protease and the polymerase, for example. So that's one thing. The monoclonal antibodies like sotrovimab, they're even more prone to kind of resistance problems because they just attack a single target. And it's on the spike protein, which is the bit of virus that's under the most selection pressure, both from host immune response and drugs or antibodies, at least. So there are antibodies in development and in fact, available that are combinations of more than one antibody. In terms of who will this be used in the future, I think, the group of patients that is always going to be an issue, even if the virus is getting less and less severe is immunosuppressed patients.They're the ones who often have quite prolonged viral shedding, can be for months and prolonged illness. They're the ones in whom antiviral resistance can develop because the virus is replicating for weeks and weeks in the presence of these things. So we're always going to need treatment for them and other very vulnerable patients, just like we do for other viruses. So if we had something better than oseltamivir for influenza, we'd be using it a lot more for example, and we should be using it in vulnerable people. So I'd think of it more like it's going to be a flu-like thing, flu-like virus that vulnerable people will still die from and get very sick from. And there will be multiple drugs available to treat it, more coming out in the future.

Dr. Caroline West:
Sarah, what are your thoughts?

Professor Sarah Hilmer:
I agree with Josh. I think the other place the field is going is for earlier treatment for immunosuppressed people who can't respond to a vaccine. So potentially either things like pre-exposure prophylaxis or very early post-exposure prophylaxis before people even get symptomatic in the same way as we do with influenza in nursing home outbreaks.

Dr. Caroline West
Well, we also see the availability of these medications with fewer pills because one of the things that I think could spook people is you go, okay, you've just got to take these four big pills twice a day for five days especially for elderly people, where swallowing,p saliva, availability in the mouth, all of those things can sort of impact their ability to take such a large number of medications.

Professor Sarah Hilmer:
Yeah. I think that's a really important area for drug development. And particularly as you say, because it is these older people who often do have trouble swallowing, who are going to continue to be the ones who need these drugs. I know that the product information for the orals we have at the moment clearly says do not crush, do not split. There is a little side note on the molnupiravir that says based on bio availability studies in five patients, it's probably okay to crush and put it down in NG tube if you really have to, but the data's just not there. So I agree. I think formulations that are more fit for purpose for the people who need to take the drugs are likely to come onto the market that are easier to take.

Dr. Caroline West:
Yeah. I think there's a recognition there that with molnupiravir that mixing it up and making it into a solution that can be orally consumed, not in tablet form may not be perfect, but it may be better than nothing. And the NPS MedicineWise website has information on aged care facilities and how that can actually be done because I guess in practical terms it may be the choice between offering it or not if somebody can't swallow.

Professor Sarah Hilmer:
And I guess you just want to be sure that the bioavailability is reasonable, otherwise just going to wind up with whole resistance.

Dr. Caroline West:
Yeah.

Professor Josh Davis:
Yeah. I think we're not far off seeing one pill once a day type drug. There's several of them in phase two and three trials for COVID. And what happened in HIV and Hepatitis C is happening in a way more accelerated way here, which is that we went from HIV, for example, people having, 30 pills, TDS type lots of side effects to having one pill once a day. I guess, a less extreme version of that.

Dr. Caroline West:
And on a personal note, this has been a time when experts like yourselves have really had to step forward and do so much extra work and really discover more about a virus, which has overwhelmed the world. Josh, if I can start with you, what's it been like over the last couple of years for you as a clinician and a researcher?

Professor Josh Davis:
Yeah, it's been really interesting and very busy. 2020 was probably the busiest I can ever remember being from a work point of view. And a lot of it was treating people's anxieties rather than real things. And I found that once we started seeing a lot of patients things settled down a bit because it was less the fear of the unknown that people had and more just dealing with reality. But yeah, it's been really busy, really interesting, exciting, things changing all the time. And I think it's good for a lot of our professions because a lot the public had never heard of infectious diseases, physicians or epidemiologists before, now they have, they know that they have a role in society. So yeah, mostly good things from my point of view.

Dr. Caroline West:
Yes the public health people have really become the heroes of the story and the scientists who've developed vaccines and medications. It's wonderful to see them applauded and given airtime to really talk about their work. And it's really helped change the course of this pandemic. Sarah, what's it been like for you during this time?

Professor Sarah Hilmer:
There are so many ways to describe it. I think disruptive and exhausting is one way. It has also been very good for, I guess, clinical pharmacologists coming together internationally and showing the role of clinical pharmacology in a sort of translational science that you need to be able to combat a disease like this. And the other thing which I think has been a real positive has been the collegiate nature of the work here and bringing together people from different health services, from different specialties and really around the world working together to really try to do our best to treat this as well as we can.

Dr. Caroline West:
Yes. I think it's been interesting at so many levels and extremely difficult, extremely disruptive. And hopefully as we move ahead, there'll be more options around vaccinations, rolling out, our understanding of exactly how often we need to provide those to get the best coverage and then the space of management treatment options. Very interesting to watch how that's accelerating so quickly. And from a community level, it is nice to see that people are gaining more confidence with living with COVID and able to resume some of the things in their lives that are so important to them and connecting with families again, crossing borders-

Professor Josh Davis:
Getting healthcare.

Dr. Caroline West:
Getting healthcare.

Professor Josh Davis:
Getting their preventative healthcare.

Dr. Caroline West:
Getting their blood pressure checked and all of those other screening tests and their elective surgery and all of the things that unfortunately have taken a backseat during this time and people have felt, "Oh, I don't want to worry the system or my doctor with this because it's not as important COVID," and I think we've got a bit of catch up to do there. I think you’re exactly right there Josh.

Professor Sarah Hilmer:
People just too scared to go to hospital. And I think people are starting to come back and that's really good.

Dr. Caroline West:
Is there anything that either of you would like to add in terms of questions that have been asked that you feel are really important to chat through before we wrap up?

Professor Josh Davis:
I think we've covered most of the things that I've been asked lately.

Professor Sarah Hilmer:
Yeah, me too. I think it's just really important to know that we do actually have treatments for early disease. And so it's worth really considering those and the early you consider them the better, your chances of being able to use an effective treatment to help your immunosuppressed or comorbid older patients.

Dr. Caroline West:
And sadly, that is all we have time for today. Thank you to our guests, Professor Josh Davis and Professor Sarah Hilmer. COVID management will be a field that's constantly evolving, so if you'd like to stay ahead with updates, go to nps.org.au. And what were those resources that you mentioned in the show, Josh?

Professor Josh Davis:
So the two main ones were the COVID Evidence Taskforce website which is covid19evidence.net.au and the Liverpool University Drug Interaction checker for COVID drugs. And there’s a link to that in the COVID evidence guidelines.

Dr. Caroline West:
Thanks for that. Now, if you'd like to send your questions in about COVID for possible future inclusion on our podcast, please go to [email protected] You can also find on our website information about CPD points. There have been no conflicts of interest declared for this podcast. Thank you for being with us. I'm Dr. Caroline West, bye for now.