PrEP: The other little blue pill

Bobby: Hi everyone and welcome to RACGP National Webinar Series. I would like to begin by acknowledging the traditional owners of the land we are meeting on here today and pay my respects to the elders, past and present. This webinar is proudly brought to us by ASHM, the Australasian Society for HIV, viral hepatitis, and sexual health medicine. Tonight’s webinar is on PrEP: the other blue pill. All GPs are now able to prescribe pre-exposure prophylaxis to prevent HIV transmission, and this one webinar will present an introduction to HIV testing and PrEP provision. I would like to introduce our presenter for tonight’s webinar, Dr Vincent Cornellise. Vincent is a Sexual Health Physician at Prahran Market Clinic and Melbourne Sexual Health Centre. His clinical practice includes HIV care, HIV prevention, STI’s, and transgender medicine. Vincent has newly finished his PhD, I am sure he is grateful for that…

Dr Vincent Cornellise: Submitted yesterday.

Bobby: There you go… and focussing on the epidemiology and prevention of HIV and bacterial sexually transmitted infections amongst men, who have sex with men. So, over to you, Vincent. Actually, we have got a few slides to go through this. So, if you can just click through the first one and the next one. Thanks, Vincent.

1:27

So, everyone who is in attendance tonight, you have got a control panel on the right-hand side there. You can either open it or hide it, depending on whether you want to see it on the side. If you would just click the next one, Vincent, everyone is muted, who is on tonight’s webinar; however, there is a provision for you to ask questions. If you do wish to ask a question, just type it in the questions log there. It will come through to us and we will filter through the questions and ask some that we feel that might be appropriate. Anything that we do not think is appropriate, we can answer after the webinar in the following days. Next one, this is you.

2:04

Dr Vincent Cornellise: These are my conflicts of interest. So, I have received speaker’s fees and advisory board fees from several drug companies involved in HIV care, and I have been a co-investigator on a couple of PrEP trials that were supported by drug companies, so in the interests of transparency, there they are.

2:25

So, thanks everyone for joining us tonight. I think this is very exciting. We have got 1200 people registered for tonight’s session, which is why you are all muted because otherwise it would turn into a bit of a crazy evening if everyone was able to talk, but I am very excited by the fact that there is so much interest in PrEP. Just to give you a bit of background, we at Prahran Market Clinic started PrEP in about 2014, initially as part of the Big PrEP Trial, and then we started assisting people to self-import PrEP through the TGA self-importation scheme, and then as part of the PrEP-X trial, and it has made a massive difference for the patients that we see at the clinic. So, I remember back in 2013-2014, I was fairly new to the clinic at the time, and I was diagnosing about one new HIV diagnosis a fortnight, and I can very happily say that over the last couple of years, I have probably diagnosed about three HIV cases in total in the last two years. So, that is what PrEP has done for us in the clinic, and I am hoping we can replicate similar trends across the country, as long as PrEP is taken up by GPs across the country. So, here are the learning objectives. I do need to go a bit fast tonight because we have got a lot of material to cover. So, our objectives are that we are first going to have a look at HIV epidemiology and the reason this is important is that it informs who should be offered PrEP. Then, we will talk about confidently identifying eligible patients for PrEP, then understanding the steps required to prescribe PrEP, and then confidently managing patients, who are on PrEP.

4:12

So, let us have a look at the epidemiology first. This is from the Kirby Institute at the University of New South Wales, and these are the new HIV diagnoses back to 1984, so annual diagnoses rates, and as you can see, the HIV epidemic really started off in 1984 and 1985, with a massive peak, and obviously many of these diagnoses were catch-up diagnoses, as in these were people, who acquired HIV in the late 70s or early 80s, and then we saw a steady decline until about the mid-90s, and then it is probably not too easy to see, but since the mid-90s, we have seen a bit of an increase year on year, and over the last five years, it has been fairly steady with sort of stable rates. This is coded by sex, so as you can see, the vast majority of these diagnoses are in men, with diagnoses in women in Australia are very uncommon. It is not that they do not occur, I do not want to erase women with HIV, but certainly, most of these are men, and that obviously signifies that this male-to-male sexual transmission.

5:18

So, currently in Australia, we have about 30,000 people living with HIV. We still see annually about a thousand new HIV diagnoses in Australia. So, this is an ongoing problem. HIV has not gone away, and we need to do more to prevent diagnoses. As I said, 63 percent of new diagnoses are currently men who have sex with men, and it is estimated, and this is based on some really clever calculations. So, it was estimated that 11 percent of people, who have HIV remain undiagnosed. Fortunately, in Australia, we find that the HIV prevalence amongst female sex workers is extremely low, so they are not really a target group for PrEP. I am not saying they cannot have PrEP, but you know what I mean.

6:04

So, why do we need to talk about PrEP. Well, as I said, the HIV diagnosis rate has remained stable over the last four years. We have not been able to get it down any further, despite ongoing promotion of condom use and frequent testing. So, we need something new. We need a new strategy, and that is where PrEP comes in. So, PrEP is a complete game changer. It gives people the opportunity to very, very effectively, and we will talk about the effectiveness rates, but it gives people the opportunity to very effectively prevent themselves getting HIV, and we have seen population that it will impact internationally. So, in San Francisco, they have seen about a 50 percent drop in HIV diagnosis rates since they started PrEP. Not all of that is due to PrEP, some of that is due to other public health strategies, but it is certainly a very dramatic drop, and in Australia, we’re internationally recognised now as being a very rapid adopter of PrEP, so we have not had PrEP that long. We have only really, while we have had it on the PBS only since April this year, and before that, it was only part of some roll-out demonstration projects, but we have had a really rapid adoption of PrEP amongst target communities, so particularly amongst men who have sex with men. And, I have to say that largely as a result of really active engagement in the gay male community and lots of health promotion within that community by the community.

7:21

So, what is PrEP? PrEP stands for pre-exposure prophylaxis against HIV. It is basically the situation is in PrEP, a person who does have HIV takes a pill every day and that prevents them from getting HIV, if they are exposed to HIV. So, if that person, who is on PrEP, and was taking PrEP every day is exposed to HIV, they are not going to get HIV. As I said, it has been on the PBS since April, and it can be prescribed by any medical practitioner in Australia, and in some states, it can also be prescribed by nurse practitioners, including here in Victoria. So, that means you presumably because I am presuming you are all medical practitioners, you can prescribe PrEP.

8:20

So, how do we know that PrEP works. We have got lots of international studies and Australian studies to look at the effectiveness of PrEP, and these studies back up the effectiveness of PrEP in men who have sex with men, in heterosexual adults, and in people who inject drugs. Unfortunately, transgender people have not been well-represented in PrEP studies. There just have not been a large number of trans people included in these studies, but data from the iPrEx study, which did include some trans-women, this data suggested that PrEP is or should be effective in transgender people, if they take it correctly, so as in take a pill every day, and there are some pharmacokinetic studies that have looked at only what would be the effectiveness of PrEP if people take it every day, and it is very close to a 100 percent risk reduction, or a 99 percent HIV risk reduction, which is outstanding, particularly if you compare that to condoms. Obviously, condoms work very well, if you use a condom, and if you have a condom on you for starters when you are about to have sex, and you remember to put it on, or you remember to get your sexual partner to put it on, and if it stays on during the entire act of sex, and it does not break, and it does not fall off, then condoms work really well, but unfortunately, that does not always happen, so the overall effectiveness rate for condoms in typical use is estimated to be a 70 percent HIV risk reduction. So, PrEP works better than condoms.

9:46

So, this is a map of the global estimate of PrEP use to date, and I say with a little bit of pride that Australia features very brightly on this map. We are a small country population-wise, but we have had a massive uptake of PrEP use, and as I said, that largely goes to collaboration between medical professionals, researchers, and the gay community itself.

10:11

So, it is currently estimated that around 15,000 people are on PrEP in Australia, so that is people who are at moderate-to-high risk of HIV, and these numbers are expected to grow, now that PrEP is on the PBS, and early reports have suggested a drop in new HIV infections. This, you know, notification data always lags a bit, but it is very exciting that in New South Wales, where they conducted the EPIC study, EPIC New South Wales, and they have now found this state-wide drop in HIV diagnoses of 35 percent since EPIC started, so that is fantastic. We are yet to see this replicated across the country, but I am hoping that as PrEP gets rolled out more widely, we will see similar drops right across Australia.

10:56

So, this is just looking at the number of new HIV diagnoses in Sydney by year, so going from 2010 to this year, and you can see there has been a really significant drop in the South East Sydney and Sydney Local Health Districts.

11:11

So, let us talk a bit about the safety of PrEP. So, the main safety concerns around PrEP relate to tenofovir, so PrEP is a combination pill of tenofovir and emtricitabine, so two drugs together in one pill, and most of the safety concerns relate to tenofovir. Emtricitabine is a fairly innocuous drug that does not have many side-effects. So, the main things to consider in terms of safety are renal functions or kidney health, and we will talk about that separately, but basically, in the PrEP studies, they have found there is a small risk of some renal impairment in people on PrEP, but the good news is that this was mainly found or mainly limited to people over the age of 40, and people who already had abnormal kidney function at baseline, so people who had an eGFR of less than 90 at baseline. So, people who are under 40 and have normal renal function have essentially a 0 or very to very low risk of renal dysfunction from PrEP use, but it is important that people have their renal function tested at baseline and are monitored ongoingly during PrEP use. There is also a small risk of reduced bone density. The PrEP studies found about a 1-1/2 to 2 percent drop in bone density, and that occurred in the first six months of PrEP use, and with ongoing PrEP use beyond six months, there was not an associated ongoing bone density loss, so it seems to be just the initial dip, and then when people stop PrEP, they recover their bone density within 6 to 12 months of stopping PrEP. Fortunately, in these randomised controlled trials, the reduced bone density of 1-1/2 to 2 percent in the PrEP group was not associated with an increased fracture rate, so we are yet to see whether this is clinically significant or not. My approach to this is that in young people, who are otherwise fit and healthy, I do not worry about bone density, but if I see an older person, so if I see someone who is aged 60 or 70, who wants to start PrEP, then I would do a bone density test before starting. We also need to think about hepatitis B, so we will talk later about hepatitis B testing, and how this is important in PrEP use, and the other risk or safety concern is the risk of anti-retroviral resistance in people who seroconvert during PrEP use. This is really rare. People who take their PrEP properly will not seroconvert, as in they will not get HIV, and hence they will not get anti-retroviral resistance, so they will not get resistance to HIV treatment. The main risk is when people start PrEP without knowing that they have HIV, they can get resistant. So, it is really important that when people start PrEP, that they have a HIV test, and we will talk about HIV testing a bit later on.

13:53

So, when might you recommend or start PrEP? So, there are really two scenarios to consider. So, one is a patient comes into your office and asks to start PrEP. Those cases are really easy. If someone comes in and they ask about PrEP, they are usually at risk of HIV. People do not come in asking about PrEP because they have no risk, and they are usually primed and ready to talk about their sexual risks because that is what they have come in to see you for. So, that is really easy, and we will talk about the eligibility criteria and the guidelines in a second. The second category is where you are seeing a patient, and you are thinking that you may need to talk to this person about starting PrEP, so the patient has not brought it up, or you are worried that they are at risk of HIV, and this is, I think, really important because GPs can play a key role in this. There are many people who are undiagnosed, as we said, about 11 percent of people who have HIV do not know that they have HIV, so they have not been tested, and the remaining people who are at risk of HIV, who do not know that they are at risk of HIV; they do not realise that their life puts them at risk of HIV. So, these people would really benefit if their doctors, so their GPs can bring this up with them, and this does require taking a sexual history on a routine basis for most of your patients. So, anyone who is of an age where they may be likely to be having sex, you should be ideally checking a sexual history, so that you can work out their HIV risk and then you can work out whether they should go on PrEP.

15:28

So, who in Australia are the priority populations for HIV testing? So, let us have a quick look at this because these are also the groups, who should potentially be assessed for starting PrEP. So, in Australia, this is really gay men and other men who have sex with men, and the second part of the sentence is really important, not all men who have sex with men are gay men. There are plenty of married men, as in heterosexually married men because we can now also get gay married. There are plenty of heterosexually married men who also have sex with men. So, it is important that if you are taking a sexual history and someone tells you that they are married, please also ask them if they have sex with other people other than their spouse. Aboriginal and Torres Strait Islander people are a potential risk group and we have seen a very dramatic increase in HIV diagnoses in indigenous communities in Northern Australia this year, so this is a hot topic and needs significant attention and investment. People who come from countries that have a high HIV prevalence and their sexual partners, so people who have migrated from say West Africa; these people may be at risk of HIV and need a HIV test; and if they are planning to go back to those countries, they may also need to have PrEP for their travels back. Travellers are traditionally very high risk of sexually transmitted infections and HIV. When you go travelling, you change your mindset, you are outside of your usual social controls, and you are much more likely to have sex with new sexual partners, and you are maybe under the influence of drugs or alcohol while doing so and may not use condoms while doing so. So, whenever someone goes overseas, it is a good idea to ask them about what they plan to do sexually, whether they plan to have sex whilst they are overseas, and then consider talking to them about PrEP. Travellers are a bit of a special category because they often do not meet the eligibility criteria for PrEP in the PrEP guidelines because they may not have a past history of HIV risk, as in their life here in Australia, they may not be at a particularly high risk of HIV, but that risk can change dramatically if they go on a holiday and have condomless sex during their holidays. So, just keep that in mind; they may not meet the risk criteria according to the guidelines, but they may actually need PrEP. People who do sex work may need PrEP, particularly men who do sex work, people who inject drugs, and people in custodial settings. Now, I do not know if any of you work in custodial settings, but obviously that adds a whole lot of layer of complexity because funding of custodial healthcare is outside of Medicare, but I guess we do not really have time to discuss that right now, but they should certainly be considered for PrEP.

18:22

Just to have a quick chat about HIV risk from individual sexual acts. I do not want to go through all these numbers, but I just want to highlight the top number on this column; 1/70; and that is the risk of HIV transmission per exposure, and in this case, the exposure is receptive anal sex with ejaculation, so if someone has bottomed and someone has ejaculated inside their bottom, then the risk of transmission if that person they are having sex with has HIV and is not on anti-retroviral treatment, the risk is 1/70 per act, which may not be as high as some of you thought it might be, but it is the highest risk, so people who have receptive anal sex without condoms are at extremely high risk of HIV, if that receptive anal sex is with casual partners, particularly if they do not know whether those casual partners have HIV. I do want to highlight at this point that the last part of that sentence, that the person who is not on anti-retroviral treatment, is a really important part of that sentence in that if someone has HIV and if they are on treatment for HIV, which means that they have an undetectable viral load, then they cannot transmit HIV to their sexual partners, and that is really important; that is backed up by really massive studies now, the Partners study and the Opposites Attract study here in Australia; and we can now say with absolute confidence that if someone is on treatment and has an undetectable viral load, they cannot transmit HIV to their sexual partners. That has been referred to as treatment as prevention, and it is important to be aware of these because A, we do not want to stigmatise who are living with HIV, but also it means that if someone’s only exposure to HIV is from their regular partner, who is on treatment and has an undetectable viral load, and if they do not have any other sexual partners, then the HIV-negative person in that couple probably does not need PrEP because they are not at risk of HIV from their regular partner, who is on treatment with an undetectable viral road. Sorry, I have the same thing three times now, just because I think it is an important point. So, let’s keep moving.

20:38

So, as I mentioned before, in order to work out whether someone is at risk of HIV and in order to work out whether they need PrEP, we need to take sexual history. So, this needs to be done as a routine. Every new patient who comes to your clinic, who is of an age where they may be having sex, so say from the age of you know 13 upwards, up to the age of say 80. Having said that, I am not joking with the upward range of 80; one of the last HIV diagnoses I made before we really started ramping up PrEP was a gentleman, who was aged 72 and had recently acquired HIV. So, older people who have sex too and we need to recognise the sex lives of older people, and we need to support older people in having safe and enjoyable sex lives. So, in order to take a sexual history, and I do not need to tell you all of this because I am sure as GPs, you are all very comfortable and competent at taking histories. There is something special about a sexual history though, and that is that you do need to explain a bit more in detail before you start the history, why you are taking this history, so that the patient is not surprised about you bringing it up, and the way I usually approach it, and it is easiest with new patients. I think it is much difficult with the patients, who you have been seeing for years, and who you have never taken a sexual history from, and then all of a sudden go, or by the way, now I am going to ask you questions about your sex life. It is much easier to do when you see a patient for the first time and you say, well, you know, we have taken your past medical history, social history, I have talked to you about smoking, alcohol etc., and your family history, I routinely also ask all my new patients about their sexual history; would you mind if I ask you a few questions about your relationships and partners, and that is usually an easy way, and people do not ever object when I say that, so it is important that you explain that, and it is also important that you only ask the questions that you need to ask. I think I am sure none of you would, but there is a risk that sexual history taking can become voyeuristic, so it is important to keep in mind that you must only ask the questions that you need in order to establish whether someone is at risk of HIV.

22:59

Bobby: Can I jump in there there for a second?

Dr Vincent Cornellise: Yes.

Bobby: There is another question coming through about patients with HIV, who are undetectable, can they become detectable?

Dr Vincent Cornellise: So, they can become detectable if they stop their treatment, and with the older treatments that we had, we certainly did see people break through their treatment, and that is probably to do with that the older HIV treatments were not as potent as the current treatments that we have, and they have more side-effects, so people have more side-effects from taking their drugs, so they were probably more tempted to take breaks from taking their treatments.

Bobby: And what sort of a break could break constitute, like if someone stops taking their medication.

Dr Vincent Cornellise: Yeah, so if someone stops taking their medication for a week or so, you would probably start seeing a viral load…

Bobby: So, then you would have to re-test them?

Dr Vincent Cornellise: Well, yeah, so, that is getting into HIV management, which is you know a bit complex, so then you may start doing things like HIV genotypes to make sure they do not have resistance, but it really depends on the situation, but I guess the important bit is that particularly with the modern, sort of the latest treatments, which most people are on, the chance of them having an undetectable viral load is extremely high, sort of you know greater that 95 percent, and the vast majority of those people maintain that undetectable viral load for the duration of their treatment, and hence there is no risk of transmission.

24:21

Bobby: Can we do a little bit of a myth buster section as well?

Dr Vincent Cornellise: Yes.

Bobby: Does circumcision make any difference to the risk of HIV transmission?

Dr Vincent Cornellise: Circumcision does make a difference, but it only makes a difference to the person with the penis, so if you have insertive sex, so you insert your penis into someone else’s genitalia or anus, if you are not circumcised, you have a much higher risk of getting HIV from that person than if you are circumcised. So, circumcision is an effective method of preventing HIV transmission. We do not rely on it here in Australia because we have better ways of preventing HIV. It has been used as a HIV prevention strategy in resource-poor settings in Africa.

Bobby: Okay, thanks.

25:10

Dr Vincent Cornellise: No problems. So, let us talk about the steps that we need to cover in order to prescribe PrEP. Now, this comes from the ASHM resource, which is available in the resource box.

Bobby: It is in the handouts.

Dr Vincent Cornellise: Sorry, in the handouts. So, if you click on that, you can download it right now, and then you can have a look at it whilst we are talking about it. There are five steps. The first step is assessing someone’s behavioural eligibility, so does their current life put them at risk of HIV? The second step is clinical eligibility, so that really consists of making sure that they do not already have HIV, and making sure that they have no medical problems that would cause a potential problem when they start PrEP? The third step is other testing, which is really STI’s and other blood-borne viruses; and then the fourth step is, actually prescribing PrEP, which we all get very excited about because we all love prescribing. And then the fifth step is, what do you do to provide ongoing monitoring, so ongoing safety monitoring for someone on PrEP. So, let us have a look at each of these steps in detail.

26:17

This is the handout, which you can all download. It is a two-pager. I would strongly encourage you to download it or at least have the web address somewhere; it is for reference because it makes it really, really easy to prescribe PrEP. You literally just follow the steps, and at the end of it, your patient has PrEP.

26:32

So, step 1, the behavioural eligibility, so you need to assess whether someone is at HIV risk if you are going to work out whether they need PrEP, and that HIV risk, which is described in the handout is from the ASHM PrEP Clinical Guidelines. Basically, high-risk groups are, it has been divided into men who have sex with men, trans and gender diverse people, heterosexual people, and people who inject drugs. Each of these groups has a separate risk criteria, and in order for someone to get PrEP on the PBS, they need to be classified as either medium or high risk of HIV. That is just so that they can get PBS-subsidised PrEP, so that is to meet the streamlined authority criteria. However, if someone comes to you asking for PrEP and they do not meet the criteria, they are according to your criteria not at medium to high risk of HIV, then I would encourage you to consider supporting that person in self-importation of PrEP. So, just because they are not eligible for PBS-subsidised PrEP does not mean that they cannot have PrEP, so they can self-import and we will talk about self-importation a bit later, and the reason I think that is important is that within the PrEPx study, we looked at the people who are enrolled onto PrEPx, who did not meet the criteria, so in PrEPx, we enrolled everyone, as in anyone who came in asking for PrEP was advised to go onto the trial, and so we could do an analysis looking at, you know, what was the HIV-risk of the people who came into the trial and who did not meet the eligibility criteria at baseline, and we found that those people, who did not meet the criteria still had a significant risk of HIV. So, if someone comes in asking for PrEP, even if you cannot find a risk, they probably have a risk because otherwise, they would not be coming and asking for PrEP. Sorry, that is my soap-box moment.

28:23

So, this is a quiz, I think. So, let us ask a question. This is for you to answer yes or no, and a little pop-up will come up in a minute, and then if you can please answer quickly yes or no, and then we can move on to the next one. So, if someone has receptive condomless anal intercourse, so they bottom with a male sexual partner of unknown HIV status, and they think that they will have multiple episodes of condomless anal sex in the next three months, so they have had a history of condomless anal sex, and I think that they will have a future likelihood of condomless anal sex, are they eligible for PrEP?

29:04

I will give you 30 seconds. So, please click your button now. I feel like a game show host right now.

Bobby: It is a little bit like a game show. You have 70 percent of the vote in with 97 percent saying yes. So, it is 3 percent, who said no.

29:29

Dr Vincent Cornellise: Perfect. So, yes. If someone has receptive condomless anal sex, in particular because that is the highest risk, and they think that they will have condomless anal sex in the future, then they are eligible for PrEP, particularly if that sex is with casual partners because with casual partners, you do not know whether they have HIV.

29:45

Next question. So, if someone shared injecting equipment with a gay or bisexual man of unknown HIV status, and they think that they will share in the future in the next three months, are they eligible for PBS-funded PrEP, tick tock?

30:01

Unfortunately, we don’t have any prizes. No prizes on this game show. A very poor game show.

Bobby: We have got 70 percent in again, and 95 percent say yes, 5 percent say no.

30:24

Dr Vincent Cornellise: 95 percent said yes. Okay. And yes, 95 percent of you were correct. So, if someone shares injections, so the important bit of this; I am just going to back to this one, but the important bit of this is that they were sharing injecting equipment with someone who is a gay or bi-sexual man and by virtue of their injecting partner being a gay or a bi-sexual man, they are at extra high risk of HIV, even though that person is of unknown status. Basically, the way I see it, if someone is of unknown HIV status, we just assume that they have HIV because unless you can show that they do not have HIV, they are a HIV risk.

30:54

Next question. Condomless sex with a heterosexual partner not known to be HIV negative but from a country with high HIV prevalence and planning to have more episodes of condomless sex over the next three months? Yes or no.

31:11

Bobby: Again, I have got 70 percent in and 93 percent say yes, 92.

Dr Vincent Cornellise: Yes, well, yes. So, it is again, it is this is pre-test probability business. So, yeah, this person has a partner who is from a high prevalence country, who has not had a HIV test, so we must assume that, that person may have HIV, and hence this person is at risk of having HIV. So, until, you know, if that is their only partner, until their partner goes in and gets a HIV test, this person should be offered PrEP.

31:50

Next question. Male having protected intercourse with a sex worker in Australia. So, having sex with a condom with a sex worker in Australia and is planning to have oral sex without condoms with a sex worker in Australia, so has protected vaginal or anal sex with a condom, but is planning to have oral sex without a condom, what do you reckon?

32:13

Bobby: So, we have got 70 percent in, and a third say yes and two-thirds say no.

32:31

Dr Vincent Cornellise: Oh, controversial. So, two-thirds of people say not eligible and one-third says eligible. Once again, you are correct. The majority rules. So, this person is at low risk of HIV unless they have any other HIV risks, but sex particularly with a professional sex worker, as in sorry, I should say someone who works in a brothel or another licensed sex service is at a very low risk. Sex workers in brothels in Australia have a very low rate of HIV, and they get HIV tested every three months.

33:07

Next question. Men having condomless sex with a HIV-positive man, who has a sustained undetectable viral load. Should this person, I have already given this one the way, should this person…

Bobby: we will see if people were listening.

Dr Vincent Cornellise: Yeah, over to you.

Bobby: Well, we have got 70 percent in, and 25 percent of people were not listening.

Dr Vincent Cornellise: So, 25 said yes because the answer is no.

33:42

So, for the benefit of those people who said yes, I would go to say this out loud again. So, if someone has HIV and they are on treatment, and they have an undetectable viral load, they cannot transmit HIV to their sexual partners. It is that, as you know, we do not often say cannot in medicine, but this statement is backed up by really solid evidence. They cannot transmit. So, if it is a couple and the positive partner is on treatment, an undetectable viral load, and there is a negative partner; if the negative partner has other sexual partners, then that is a different story. If they have other sexual partners, then they may be at risk from the other sexual partners and may still need PrEP, but they are certainly not at risk from their regular partner, who is undetectable. So, well, I am going to hammer on about this even more.

34:30

So, undetectable is untransmittable, and there has been a global campaign now to promote this message, and the reason it is being promoted so widely is because it is so important for people living with HIV, and now people who are living with HIV have lived in fear for years that they may pass HIV to their sexual partners. No wants to pass HIV to their loved ones, their sexual partners, or their friends with benefits. So, this has been a big issue and we finally now have really good evidence to show conclusively that undetectable is untransmittable.

35:10

So, let us go on to the next step in prescribing, so the clinical eligibility. So, in order to confirm that someone is clinically eligible, so you have established that this person needs PrEP, and now in order to confirm that they are clinically eligible, you need to check their HIV status, so they obviously cannot HIV. If they have HIV, they must not start PrEP. So, you need to do a HIV test. You also need to ask them about symptoms of acute HIV infection. As I am sure you all know, HIV tests have a window period and if someone has an acute infection, it may not show up on their HIV test yet, so if they show up with fevers and sweats, and swollen glands, and maybe a rash and a sore throat, you have a high index of suspicion that they may be seroconverting to HIV, if they fall in a HIV-risk category, which by definition this patient does because you are considering PrEP for them. They need to have a normal renal function; it does not have to be entirely normal but needs to be an eGFR of greater than 60, and they probably should not be taking any nephrotoxic medication, but we will talk about that in a bit more detail. Now, importantly, when you are seeing a patient and you have taken their sexual history, and you are planning to prescribe PrEP, you need to ask if they have had a significant HIV exposure or significant possible HIV exposure within the last 72 hours, because if they have had a significant possible exposure in the last 72 hours, then they need to consider PEP or post-exposure prophylaxis. PEP and PrEP are two sides of the same coin. PrEP is pre-exposure, PEP is post-exposure, but the follow-up regimen is different, and in some people, who go onto PEP or post-exposure prophylaxis, we use three drugs rather two drugs, so PrEP is tenofovir and emtricitabine, PEP can be tenofovir and emtricitabine in fairly low-risk exposure, but in high-risk exposure, it can be tenofovir, emtricitabine, plus a third agent.

37:18

So, it is important that there is a difference.

37:21

So, if someone has a risk within the last 72 hours, then they should really be referred to a PEP clinician, so that is either a PEP service, so I will move on to this one. Oh, I am skipping ahead.

37:33

So, where do patients get PEP? So, they can get PEP from any hospital emergency department or any HIV s100 prescriber. So, in Australia, I do not know if everyone is aware of this, but HIVs in Australia is prescribed by GPs often, but these GPs have had further education in HIV management and as such are classified as s100 prescribers for HIV medicine. They can prescribe PEP and any hospital emergency department can prescribe PEP, and that needs to be started within 72 hours of a high-risk exposure, but the sooner the better. So, if they can start it within 24 hours, that is even better.

38:17

If you are not sure where to find PEP for your patients, here are the phone numbers. We will email these to people after the...

Bobby: Everyone will get access to the slides.

Dr Vincent Cornellise: Okay, everyone will get access to the slides, so you will have these numbers at your disposal. So, that’s PEP.

38:32

So, what if a patient tests positive for HIV because you are going to do a HIV test on these people, anyone who is going to start PrEP is going to have a HIV test. It is important to recognise that most HIV diagnoses in Australia are made in general practice. So, you know, the unfortunate reality is that some of you will diagnose people with HIV over the next couple of years, as we are driving up HIV testing. Obviously, as we are driving up PrEP, we are also going to increase HIV testing, hopefully, that is what we are aiming for, which means we will diagnose more people with HIV, who have been living with HIV for perhaps some time. There are specific resources in place in some states and territories to assist GPs, who have just made a new diagnosis, and ASHM does provide practical resources to support clinicians, who have made a new HIV diagnosis. At this point, I do need to make a point, again getting on my soap-box because I have talked a lot to the community, and there has been concern in the community that there have been cases where GPs have recommended…. so, what has happened in the community, and this has been raised by community organisations, what has happened is that people have been diagnosed with HIV and then the treating doctor has recommended to them that they talk to the police about the person who may have given them HIV, and I have been asked by the community to raise this tonight and say, can we please make sure that does not happen. Intentional HIV transmission is extremely rare. There have been a few cases like literally having two or three cases in Australia for the entire duration of the HIV epidemic, where people have been convicted of intentionally transmitting HIV. It is extremely rare, and it is really not helpful if people start referring people to the police. Sorry, I know that it probably seems to be really obvious, but I have been asked to say it, and I do think it is important because we need to make sure we do not increase HIV stigma and in fact, we should actively work to de-stigmatise HIV by providing support to people living with HIV and not getting the police involved.

40:52

So, very practical, what HIV tests do you order? You order HIV antigen/antibody tests, easy, and Australian labs are now all using the fourth generation HIV antigen/antibody combination tests, and the fourth-generation test has a quite short window period. So, it becomes positive two to six weeks after exposure, which is great for starting PrEP because previously we had window periods of up to three months on our HIV tests or the third-generation HIV tests. It makes it really difficult to confidently start someone on PrEP when you are not really sure whether they have HIV or not. I should say something else about window periods because I have had this question come up quite a few times because prescribers often worry about starting people on PrEP, who may have had an exposure within the window period, which happens a lot. So, if you all were seeing people, who were at risk of HIV, chances are they have had sex within the last six weeks. If they have not had sex in the last six weeks, they probably do not need PrEP, so it is very common to start people on PrEP when they are still within the window period of the HIV test, and can I just reassure everyone that, that is fine. You can start people on PrEP even if they have had exposures within the window period. What I tend to do is if someone has had a high-risk exposure within the last two weeks, so not within the last 72 hours because we have talked about that. If it is within the last 72 hours, you refer them for PEP, but if they are not within the last 72 hours, but if they have had a high-risk exposure within the last two weeks, then I usually get them back at one month to repeat the HIV test. If their exposure is beyond the last two weeks, then I just test them again at three months. So, that is all sort of described in the resources as well, but just an important point that if some do not wait for people to fall outside of the window period before they start PrEP because you will never get them on to PrEP because people do not stop having sex, and those who do stop having sex do not need PrEP.

42:49

Bobby: How long after PEP?

Dr Vincent Cornellise: Oh, that is a great question. So, PEP, you can stream straight from PEP to PrEP. So, if you start someone on PEP, and they come to see you within their last week or so of PEP, you can give them a script for PrEP and they can, one day they are on PEP, the next day they are on PrEP, so they just stream straight on, and that is the best way to go because then you avoid potentially leaving them in a situation, where they may get exposed to HIV in the in-between time between PEP and PrEP, so the best thing to do is to go straight from PEP to PrEP. As we have talked about before, we do need to check whether someone has signs or symptoms of acute HIV infection, and as I said, these are fevers, tiredness, muscle aches, rash, headache, sore throat, swollen lymph nodes, sore joints, night sweats, and diarrhoea. Now, these are really non-specific symptoms, you know, if you see this in the general population, you go, ah, viral infection, but these are people, who are at risk of HIV, so if you ever see someone who has a risk of HIV, who has these non-specific symptoms, think seroconversion, which is important because then, in those situations, you are probably best off doing the HIV tests and getting them back a couple of days later to have a look at the result, rather than sending him out the door with a prescription for PrEP because PrEP is not HIV treatment. So, you do not use it to treat people who are seroconverting.

44:09

Let us talk about kidney function. So, you need to check whether someone’s renal function is adequate and to see whether they are taking any nephrotoxic medications. So, PrEP is TGA-approved for people, who have an eGFR of greater than 60. If they have an eGFR of less than 60, they really should not get PrEP, again because the tenofovir in the PrEP pill can be renotoxic. That can be tricky, as I have seen young guys, who are really healthy, and they have got an eGFR of 55, and they have lots of muscles, and they have just been to the gym, and they have got lots of, you know, creatinine released from their muscles and, you know, sometimes, they are at high risk of HIV, so in some of these guys, I have ended up doing a nuclear medicine study of renal function and found out that they have got completely normal renal function, despite having an eGFR of 55. So, sometimes, that is what needs to happen, but as a rule, an eGFR of less than 60, you cannot have PrEP. Some examples of nephrotoxic medications. We have listed acyclovir and valacyclovir for herpes treatment. They are theoretically nephrotoxic, but I have to say that I have a lot of patients, who were taking PrEP, and they would have herpes, you know, they come with the same risks. People who get HIV get herpes and people who are at risk of HIV get herpes, and I have not had any problems in people taking herpes treatment and being on PrEP. High-dose NSAIDs are a problem, so if you are seeing an older patient, who wants to have PrEP and who is taking ibuprofen every day or celecoxib every day for their osteoarthritis, then that is a problem, so they may need to find an alternative strategy to manage their arthritis, and then aspirin and aminoglycosides. I do not imagine you will see many people taking aspirin every day, but again, maybe you know, you have got older patients who have got a cardiac risk, who may be on low-dose aspirin, and that may cause a problem. Hopefully, we do not need to use so many aminoglycosides, although the way gonorrhoea is going, we may need to revert back to using gentamicin to treat gonorrhoea, but we will deal with that when we cross that bridge.

46:30

So, we also need to test for STIs and hepatitis core infection because people who are at risk of HIV are also at risk of hepatitis B and hepatitis C, and other sexually transmitted infections. This is all outlined really well in the Australian STI Management Guidelines, which are available online. For those of you who are not aware, the STI Management Guidelines are updated earlier this year, and it is a really useful website. It is not yet PDF documented, so a website with dropdown menus that is really easy to use. So, just google the Australian STI Management Guidelines, and it will come up. We may even be able to send you the link after this.

47:12

So, let us have a look at hepatitis B. So, when you order your tests for hepatitis B at baseline, which you need to do, it is really important that you test for hepatitis B at baseline because PrEP is also active against hepatitis B. So, the tenofovir in the PrEP pill is also a hepatitis B treatment, so if someone has hepatitis B, and they are not aware, and you start them on PrEP, it is fine because you are also treating their hepatitis B, and you will slowly suppress their hepatitis B viral load, but the problem then arises if they stop PrEP or if they use PrEP intermittently, so then, you know, if that patient feels that they are not always at risk of HIV and they might come off and then restart PrEP and come off, that becomes an issue because then every time they stop PrEP, they risk having a hepatitis B flare because they are withdrawing hepatitis B treatment. So, it is really important that you test for hepatitis B for that reason, but also so that you can see whether this person needs to be immunised against hepatitis B because they are at risk of hepatitis B. So, when you order your tests, make sure you order a full suite, so order a surface antigen, surface antibody, and a core antibody for hepatitis B, and just make sure in your clinical notes on the path form, you write risk of hepatitis B or something, so that the lab is happy about this because otherwise, if you just order hepatitis B serology, literally verbatim, hepatitis B serology, depending on the lab, you will get some variety of these tests back, but you do not usually get all the three of them back. Obviously, you would immunise if they are not immune, and if they have a positive surface antigen, so if they have chronic active hepatitis B, then your best bet is to refer to a hepatitis B specialist because as I said, they can probably start PrEP, but they may not be able to stop PrEP, so before they are started on life-long treatment, they should probably have a chat to a hep B specialist. If that is difficult, because, you know, some of you may be in rural locations, and you may not have access to hepatitis B specialists. If that is difficult, then potentially, they could start on PrEP, as long as they do not have evidence of cirrhosis, so do a quick workup and check the ALT and maybe get an ultrasound organised. If the liver health is okay, then they could start PrEP, and as long as they know that they cannot stop PrEP and they should not take breaks from PrEP, and then go and see a hepatitis B specialist whilst they are on PrEP.

49:38

Bobby: hey Vincent, does taking PrEP interfere with immunisation?

Dr Vincent Cornellise: No.

Bobby: If you have been vaccinated, so it does not have an influence?

Dr Vincent Cornellise: No, taking PrEP does not interfere with any immunisation, including hepatitis B immunisation, so you can start someone on PrEP and then you can immunise them and that we will be fine.

50:01

Hepatitis C. So, what tests do you order for hep C, well you…. Sorry, what did I just say… First, obviously you all order a hepatitis C antibody and if that is positive, you order a hepatitis C RNA. Now, excitingly, I get very excited about these things, but another exciting thing is that any GP in Australia can now treat hepatitis C. So, not only are you going to come away tonight being a PrEP prescriber, but you are also coming away knowing that you are a hepatitis C prescriber. So, if their antibody is positive, order an RNA to differentiate whether they have previously had hepatitis C and they have cleared it versus whether they have chronic active hepatitis C, and if they have chronic active hepatitis C, what do you do, you treat them. Now, if you have not done this before, then it is a good idea to get in contact with your local hepatitis C specialist or ASHM can put you in touch, so ASHM have an online mechanism, whereby you can get online advice on treatment. So, just go back to the ASHM website and then make sure you treat them for hepatitis C. That is PBS-funded, so patient just pays PBS price, it is usually just 12 weeks of treatment, one pill a day, pretty much no side-effects at all. The new hepatitis C treatments are amazing. You can cure them at a rate of about 98 percent, and if they get hepatitis C again because they are still injecting drugs or whatever their risk is, if they get hepatitis C again, you treat them again, and you just keep going until you cannot find any more hepatitis C. So, test everyone for hepatitis C and treat everyone that you find and just keep treating until it is gone.

51:47

We talked about this, hepatitis B, so I am not going to talk about this again. So, just to confuse or hopefully not confuse matters, but there are different ways of taking PrEP. The most studied way of taking PrEP is taking a pill every day, so one pill a day for as long as you need it, so for as long as you are at risk of HIV, so as long as you are sexually active, or you have casual partners, or you are injecting or whatever your risk is, as long as that is ongoing, you just keep taking the pill. There is another way of taking PrEP and that is to take it on-demand, so then you only take it around the time of an exposure, now that has been studied in a couple of trials in France, in the Ipergay trial and the Prevenir trial, and they have got pretty reasonable data for the effectiveness of doing that, but it is not as solid as the effectiveness data for daily PrEP, and the data is only available for men who have sex with men. There are a couple of transgender women in these studies, but really, it is mainly cisgender men who have sex with men. There is no data for transgender men who have sex with men. There is no data for women and there is no data for people who inject drugs. So, really the main message to take away from this tonight is the best way to take PrEP is to take one pill a day for as long as you need it, as in continuously, and if people cannot do that for some reason, like maybe their renal function does not allow it or there are some other issues why they cannot take PrEP every day, then perhaps on-demand PrEP is suitable if they are a cisgender man who has sex with men, but understanding that the data is not as good.

53:24

Bobby: Can you use PrEP while you are being treated for hepatitis C?

Dr Vincent Cornellise: Yes, you can use PrEP while you are being treated for hepatitis C. It is a good idea… Whenever you are combining hepatitis drugs and HIV drugs, it is a good idea to check for drug interactions because there are quite a few hepatitis C treatment regimens now, so in that case, it is just important to check that the person starts a hepatitis C regimen that is compatible with their PrEP. I have talked about this, but basically, in on-demand PrEP, so this is the Ipergay protocol. I am not going to labour this, but in on-demand PrEP, you take two pills at least two hours before sex followed by one pill 24 hours later and another pill 48 hours after the first dose, around one act of sex. It is quite complicated. Again, you can look at these slides later. You know, if you are new to PrEP, I would just say, don’t go here yet. Just start people on daily PrEP because it is so much easier, and we know it is really effective.

54:25

Just to confuse things a bit more, there are a few different versions of PrEP available, but the good news for you is that, as you long as you write a prescription that says tenofovir and emtricitabine for PrEP, the patient will get one of these versions from the pharmacist. So, they are all slightly different. They are basically just different salts of the same thing, so there is tenofovir disoproxil fumarate, tenofovir disoproxil maleate, and tenofovir disoproxil phosphate. As you can gather, they are all these different salts of the same thing, so they do the same thing. So, it does not matter, as long as this is right, tenofovir and emtricitabine, they will get what they need.

55:05

I have just got myself lost for a second. So, they are all like I said the same drug. You can use them for PEP and PrEP, but as I said earlier, sometimes for PEP, we use three drugs, and the followup for PEP is different from the followup for PrEP, so again, if someone needs PEP, as in if they have had a high-risk HIV exposure in the last 72 hours, please refer them to a PEP service. If that is not possible, if you are in Broken Hill, and you do not have access to a PEP service, and the patient sitting in front of you has recently had a high-risk exposure, and you are worried that they need PEP, I think it would be perfectly reasonable to start them on PrEP because at least you are doing something for them because the alternative would be for them to walk out of your room with nothing, but in that case, it is probably a good idea if you are not experienced in PEP and PrEP, it is probably a good idea to just phone a friend, so phone one of the PEP hotlines just to discuss the case, but I think it would be perfectly reasonable to give them a script for PrEP in that situation, and then also probably, you know, find out if the pharmacist can get it in quickly, again because of the time issue. So, if it takes a week to get the PrEP in to the pharmacy, then that is obviously not going to work.

56:25

So, as we have said, PrEP is PBS-listed as of the 1^st of April. It is streamlined, it is really easy, it is a 7580 streamlined authority code. Now, the slightly confusing thing is that there are a few different listings for tenofovir and emtricitabine on the PBS, and most of those listings are for treatment. There is only one listing for PrEP, and you can tell the difference because PrEP is the only listing that has a quantity of 30 with two repeats, and that is designed to get people back to you every three months for a new prescription, so that they have another HIV test every three months, and they have their kidney function tested, and they have their STI screens. And while you are there, you can make sure you vaccinate them and check in about their mental health and check in about their drug use and, you know, make sure that they are just generally happy.

57:15

So, this is one of my favourite slides. People who are not eligible for PBS-funded PrEP, as I yarned on about at the start, if someone comes to you and they want PrEP, but you cannot find a way to prescribe it for them on the PBS because they do not have an identifiable HIV risk, you can still assist them with self-importation. Self-importation is perfectly legal. It can be done under the TGA self-importation scheme, which sounds very complex, but it is not. It is just, give them a prescription and tell them to go to one of these websites, and they can order it, and it will arrive in the mail. There are no other special forms that need to be filled in. They do not need a Medicare card, and the good news is that self-importing PrEP has now, the cost has come down to about $23 a month, which ironically is cheaper than PBS price. So, people can now on a private prescription buy PrEP online for $23 a month, obviously PBS price for most people is $37 to $38.

58:20

Bobby: So, a question did come through, why would not you just a write a private script?

Bobby: Yeah, well, it is a very good question, why would not you just write a private script. Well, I guess the one straightforward answer is that for people with healthcare cards, it is still cheaper to get it on the PBS. The other thing is that, at least if someone is buying their medication on a PBS-funded script, and they are taking it through a local pharmacy, you can be very confident that there has been a perfect chain of custody of that medication, and there have been concerns that perhaps that may not be true for online ordering, although having said that, there has been a study at Chelsea Westminster in the UK that looked at the quality of the PrEP drugs that were coming in through these online pharmacies, and they were perfect, so there was not issue with chain of custody, and the only other issue, can I think of another issue, well they only, sometimes they get held up at customs, and sometimes they are delays, and sometimes that really messes up people’s PrEP taking when, you know, their pills get held up for a couple of weeks at customs, so that is also another issue, but other than that, there is not much difference. Oh, and as it says here, be conscious about time of delivery because sometimes it can take a couple of weeks for it to arrive if it gets held up.

59:33

And these organisations, sorry, so pan.org.au and prepdforchange.com, they are community-run organisations, and the guys that run these organisations have done a lot to promote, they are not for profit, as far as I am aware, and they have done a lot to promote the uptake of PrEP amongst people, who are at risk of HIV, so they are really community-minded, so I have a lot of confidence in these guys.

1:00:00

So, this is step 5, the final step. What do you monitor for someone on PrEP, and again, this is in that handout that I asked you to download at the start. On the back or the second page, there is a box that in the very quick-and-easy thick format shows you what tests to order at baseline, at one month, if that person is to come back at one month, and then at three months, and then ongoing. So, basically, you keep testing HIV because you need to make sure that they still do not have HIV, you check for side-effects, you check for hepatitis, that do you have a hepatitis serology at baseline, and then, as we talked about it, if they are not immune, you immunise them, so you do not need to keep checking that. You check their hepatitis C at baseline, and you re-check that every 12 months, and you do your STI testing, so testing for Chlamydia, gonorrhoea and syphilis every three months. Now, I do need to make a quick point about STI testing. Please, please, please, when you are testing for gonorrhoea and Chlamydia, can you please make sure they get an anal swab and a throat swab because if someone has gonorrhoea or Chlamydia, it is much more likely that they have it up their bum or in their throat, rather than in their urine tests, so just doing a urine test has really low yield, particularly for gonorrhoea, the swabs up their bum mainly in the throat are much more useful. Most people are quite capable of doing a self-collected anal swab. Throat swab is probably a little bit more difficult, and if you are going to do these tests, particularly for gonorrhoea, can you please make sure, you order a PCR test for gonorrhoea, not a culture because culture is really quite insensitive. Culture picks up only about 20 percent of throat gonorrhoea and only about 50 percent of anal gonorrhoea, whereas PCR picks up just about a 100 percent. Having said that, if you diagnose someone with gonorrhoea, can you please do a swab for culture before you give them the antibiotics because you need to know the antibiotic sensitivities. You do not wait to give them the antibiotics, you also give them the antibiotics, but can you please collect a sample for sensitivity testing before giving them a needle. And finally, you need to check their kidney function at baseline and ongoingly every six months, and in women of child-bearing age, please also do a pregnancy test just for good measure. PrEP is category A in pregnancies, so just because someone is pregnant does not mean that you cannot start PrEP, but it is always good to know if your patient has a baby inside of them.

1:02:31

So, ongoing monitoring also includes ongoing patient education. So, we refer to this as combination HIV and STI prevention, which basically means to try and get them to use to condoms, to reduce their STI risk. If they are injecting, talk about safe injecting techniques, make sure they have access to clean needles, you know, perhaps talk about if they are injecting heroin, perhaps talk about opioid substitution programs, if they are injecting stimulants like crystal, it is a bit more difficult to get any sort of substitution. And make sure that they understand that if they start PrEP today, they are not immediately protected. They need to be on PrEP for seven days to achieve a good level of protection, and that is important, because you do not want them to walk out of your room and go to the local sauna and have a great old time, thinking that they have full HIV protection, if they have only taken one pill of PrEP, and down the track, if they wish to stop PrEP because their situation changes and their HIV risk has declined, or because they are getting side-effects. The Australian guidelines currently recommend that people continue PrEP for 28 days after their last risk exposure, which is the same duration as PEP. And then, with your ongoing patient consultations, obviously check that they are not taking any medications that can affect renal function, including over-the-counter medications, and no gym supplements, protein supplements, that sort of stuff. Have a check-in on their mental, their recreational drug use to make sure, you know, you check whether they are having any difficulties there and need any help and check for side-effects.

1:04:06

Side-effects are quite common initially, but they are quite mild. So, a sizeable minority of patients get either some nausea, some diarrhoea, some headaches and tiredness, and maybe a bit of flatulence. The diarrhoea and the flatulence are particularly troublesome, I mean if you are on PrEP because you want to have sex, and then all of a sudden, you have got diarrhoea and flatulence, you cannot have sex, so that is a bit counterproductive, but the good news is that most of these side-effects settle down after about three to four weeks, if you would continue taking the PrEP. I often say, you know, if you can take your PrEP with a meal, that probably helps with some of the gastro-intestinal side-effects, and I find a vast majority of people, if they continue PrEP, their side-effects settle down and are not ongoing. I have only had two to three people, who have stopped because of these sorts of side-effects.

1:05:00

So, there are not a lot of drug interactions between PrEP and other medications. It is really quite clean in terms of its interaction profile, but if you are worried about interactions, like if you have got someone on anti-epileptics, or on warfarin or, you know, something that you really need to know whether there are any drug interactions, go to the University of Liverpool website, which has an online HIV drug interactions database, so their web address is up there, hiv-druginteractions.org.au and on that website, you can plug in the tenofovir and the emtricitabine for their PrEP, and then you can plug in whatever else they are on, and then the website will spit out whether there are any significant interactions. The most common issues are around non-steroidals because they affect renal function, and as I mentioned, protein powders often send up eGFRs and other gym supplements, so that can be a bit of a hassle when you are dealing with a population that also likes to work out at the gym.

1:06:08

So, again, as I have said before, just talking about renal function, if someone has an eGFR of less than 60, then they should not be prescribed PrEP. The tricky area is when someone’s renal function is either just below or just above 60, and they are at risk of HIV and trying to work out what to do, but yeah, if you have those difficult cases, feel free to give us a call. And then, you need to monitor them every either three to six months, depending on their age and their renal function. So, if they are a young person with normal renal function at baseline, then every six months is fine. If they are an older person, who may have, you know, somewhat borderline renal function, then I would monitor every months, and that monitoring consists of doing eGFR and doing a protein-creatinine ratio on their urine, preferably mid-stream urine, although I most of the time do this on first catch urine because I am also doing urine tests for Chlamydia and gonorrhoea, and it is really quite cruel to ask people to do a mid-stream and a first catch urine at the same time, and they end up juggling two urine jars, and they are not remembering which urine jar had what urine in it. So, I tend to do this protein-creatinine ratio on the first catch urine, and if it is elevated, then just repeat it on the mid-stream. This is a protein-creatinine ratio, not an albumin-creatinine ratio. We are not looking for glomerular damage. We are looking for proximal renal tubular damage, which is signified by non-albumin protein.

1:07:42

Bone, that is usually not an issue, I have talked about it already, I am not going to talk about it anymore because it is really not an issue. As I said, perhaps the only exception is older patients who start on PrEP, you want to do a bone density test, so I am talking, you know, 60 plus.

1:07:58

We briefly mentioned pregnancy, so, yeah, I do not know if you want to talk about this. There is possibly a slight drop in bone density in newborns in women who are on tenofovir, and tenofovir is secreted in breast milk, but its secretion is very low. It is pregnancy category A, so it is possible to prescribe PrEP for a pregnant woman who is at risk of HIV, obviously if a woman is at risk of HIV, the risk to the baby is much greater if she gets HIV, rather than if you can protect her from HIV with PrEP, but as I have said before, just make sure you do a pregnancy test before you start PrEP, and you know, if you are seeing a woman for PrEP, talk to her about contraception as well, and make sure that she has a failsafe contraception, as in either the pill or preferably a long-acting reversible contraception, such as the Implanon or the Mirena.

1:09:00

Adherence is very important for PrEP. PrEP does not work if you do not take it, so make sure that people understand that they need to take it every day, and try to support them in their adherence, so they are apps you can get online at your friendly app store that support pill adherence, or people can just set an iPhone reminder, or try and incorporate it into their daily routine. They will keep your PrEP bottle next to your toothbrush, and so that when you brush your teeth in the morning, you also take your PrEP pill, find a way that works. I always recommend that people get one of those dosette boxes, you know, Mondays through to Sunday, and then they give me really funny looks and say, You know, ‘I’m not a granny’, and I’m like’ well you know, just use it, it works’ and people then usually do.

1:09:44

We talked about stopping and starting, so I am for the sake of time not going to talk about that, and we have talked about the three-monthly reviews already, and we have talked about condoms and needles. So, we do encourage people to use condoms, not because we do not believe that PrEP works, but just because we are seeing a lot of other STIs. These are the guidelines, which you can look up later, and now, let us move on to cases.

1:10:08

Bobby: Perfect. There are six cases that we have got today. We will see how we go. We may just cover the first few depending on how long they take to get through. Just to clarifysomething before I move on because there have been a few questions around the private script versus importation stuff. The preference obviously would be to get it locally and have an Australian pharmacy dispense PrEP if we can. So, that would mean writing a private script. Patients would obviously pay more for that private script.

Dr Vincent Cornellise: as in for people, who are not eligible for PBS-funded pessary. It is really not affordable privately. So, they are looking at probably at 700 a month, privately from a local pharmacy. So, it is really, you know, they have been very few people who find that a feasible proposition. So, really, the only two options are a PBS-funded script for a local pharmacy or a private script for self-importation.

1:11:00

Bobby: Yeah, and that you could write a private script, if someone was willing to pay that 800 to get PrEP through a local pharmacy that, that could be an option for those people.

Dr Vincent Cornellise: It is an option. The other thing is, yeah, if someone is willing to pay that much money for PrEP, I would ask them a few more questions and work out, you know, what is going on because they probably do have a significant HIV risk because otherwise why are they willing to pay so much money for HIV prevention.

Bobby: Yeah.

Dr Vincent Cornellise: So, maybe that is just a signal that we need to take a bit more history and work out if that person is actually eligible for PBS-funded PrEP.

Bobby: Great, thanks very much for that clarification as with case studies.

1:11:42

Dr Vincent Cornellise: Cases. So, there were no other, there were not any questions?

Bobby: Oh, there are other questions here, but I think we can answer offline.

Dr Vincent Cornellise: Okay, good. Case study 1. Mark. So, Mark is a 34-year-old man, who identifies as gay, and he has heard about PrEP from his friends. He regularly bottoms with casual partners, so he has receptive anal sex, and this is with casual partners he meets on Grindr. Now, for those of you who may not be aware, Grindr is what we technically call a geospatial networking app, which shows you where the next available person is for sex, while not technically aware, but shows your closest available person for sex. He reckons he is pretty good at using condoms most of the time, but he has had a few slip-ups, and really, he does not like condoms. Look, to be honest, no one likes condoms. I think we need to recognise that. Condoms were not invented to enhance sexual pleasure and he really wants to bare back, as in he wants to have anal sex without condoms. Does he meet the behavioural eligibility criteria? Do we go to the next?

1:12:49

So, let us have a look at the criteria. So, this again is on the handout that I got you to download at the start. And this is from the column for eligibility criteria for men who have sex with men. So, the criteria say, the high-risk criteria are condomless anal intercourse or CLAI with a regular HIV-positive partner, who is not on treatment, receptive condomless anal intercourse with any casual HIV-positive male partner, or a male partner of unknown status, and that last bit is the important bit, unknown status. So, if someone does not know their status, they could have HIV, or if someone has a rectal gonorrhoea, a rectal Chlamydia, or an infectious syphilis in the last three months, or if they use methamphetamine, so particularly crystal meth, I find, rather than speed, and if they plan to have anal sex without condoms, or share injecting drug equipment in the next three months. So, obviously Mark does meet the criteria. He has sex with male partners of unknown status, as in he meets guys casually on Grindr and obviously cannot verify their HIV status, so you must assume that they could have HIV, and he has expressed the desire to not use condoms in the next three months because he wants to bare back. So, what is your next step?

1:14:10

Yes, he is eligible, and you move on to clinical eligibility. So, you have established that he is behaviourally eligible and now we want to check that he is clinically eligible, so you want to check that he has no signs or symptoms of acute HIV infection; he does not report any high-risk exposures in the last 72 hours; he does not really have any medical history; he is a young guy; he is healthy; he does not take any medications; no supplements; no over-the-counter medications. So, you discuss PrEP in detail, including the dosing, the side-effects, and the followup. What do you do next? It is great that we have got so many people online, but this would be great in a small group.

1:14:52

So, your next step is, you order his other tests. So, you order his HIV tests, his kidney function, including his eGFR and his urine protein-creatine ratio, not his albumin-creatinine ratio. Sorry, sometimes typos happen. You check his hepatitis B, hepatitis C, and syphilis serology, and if he is not immune to hepatitis B, you give him hepatitis B immunisation, and you check his tests for gonorrhoea and Chlamydia by doing an anal swab, a throat swab, and a urine test, and you send that off for PCR testing. You give him a prescription for three months of PrEP, one tablet a day, and you ask him not to start just yet because you wanted to get back to him with his HIV result and his kidney function result before he takes his first pill.

1:15:43

So, because you are in the middle of a city, you receive your results back the next day, and you find that he does not have HIV, or least his HIV test is negative; his renal function is normal; he does not have proteinuria; and he does not have any STIs or blood-borne viruses. So, you tell that he can start PrEP, and you remind him again that he needs to be on PrEP for seven days before he can rely on it, so do not go to that party tonight, and that if down the track if he wants to stop PrEP because he may not come back to see you, you hope that he does, but you know, it is possible that he does not, so you remind him that if down the track, if he wants to stop PrEP, he should continue for 28 days after any potential HIV risk exposure.

1:16:17

Bobby: And if he wants to start again, he has to go through the same protocol then you went through the first time, all those same tests…

Dr Vincent Cornellise: All the same tests, all except, you know, the hepatitis B tests, but all the other tests, he needs to definitely have a HIV test because we need to make sure that in the intervening period, when he was off PrEP that he did not get HIV. That is the most important bit. Oh yeah, basically you just start from scratch.

Bobby: Start from scratch.

1:16:55

Dr Vincent Cornellise: So, when do you ask him to come back? Well, in Mark’s case, it is pretty straightforward. Just get him back in three months after starting PrEP. When he comes back, he says, “I have had some headaches for a few days after starting, but otherwise that went fine. No issues. I am taking my pills every day. I have got a good system in place. I am using an app to remind me, the one called round that he found on the app store, and that he does not have any STI symptoms.” You have a chat to him about what is going on in his sex life and what he is doing in terms of condom use to prevent STIs, recreational drug use, and just check again that he has not started any new medications since you last saw him. So, all is well. You give him another three months of PrEP to take every day, and you order the routine three-monthly tests, so HIV tests, kidney function tests, and STI tests, and again, anal swab, throat swab, urine tests.

1:17:50

Bobby: How about non-compliance?

Dr Vincent Cornellise: Yeah, so when PrEP first came along, so the question is, what do you do about non-adherence to PrEP, and when PrEP first came along, that was a big question mark. We were very worried that if people were going to start PrEP, they were not going to take it properly, and then they were going to get HIV, and then potentially it could do harm by making the HIV resistant to the PrEP medication, which then limits their HIV treatment options. The reality is that this has not borne out. So, there have been a lot of large cohort studies that have shown that when people take PrEP and they know that they are taking PrEP, so this is not from the randomised control trials, where people were taking either placebo or PrEP. They had some issues with adherence because people did not know whether they were taking PrEP or not, but in the trials where people knew that they were taking PrEP, their HIV rates have been very low and suggesting their compliance has been very high. So, even though that has been a concern, it is not a reality. People who start PrEP are generally, as long as they are informed properly, they are very adherent to their PrEP medication because they understand the importance of taking it every day.

1:18:57

Bobby: If someone does miss a dose though, what do you do, if they called you and they say, I missed my dose, what would you tell them?

Dr Vincent Cornellise: If someone misses one dose, to be honest is not an issue at all. Tenofovir has quite a long half-life, so they get a slight dip in their serum tenofovir levels and plasma tenofovir levels, but not enough to compromise the effect of this. What I tell people generally is, so have your routine in place, and if, you know, halfway through the day you realised that you forgot to take your PrEP that morning, just take it then. If you get all the way to the next day, just continue as usual. If you have missed a few days, if for example, you have left your PrEP at home, and you went to visit your parents out in Broken Hill, and you thought you were not going to have sex, but then all of a sudden, you ran into a very lovely person, who you wanted to connect with, but you had forgotten your PrEP, then I would say, if you missed a couple of days or three days or four days, use condoms, and then restart your PrEP, and then make sure you are on it for seven days before you can rely on it again. Case study 2, or unless there are any questions.

1:20:02

Bobby: None specific.

Dr Vincent Cornellise: None. Okay. So, case study 2 is Steve. Steve is 43….

Bobby: Oh, sorry, why urine PCR in his case…someone did ask.

Dr Vincent Cornellise: For Chlamydia and gonorrhoea?

Bobby: Well, that is what it was, okay, sorry.

Dr Vincent Cornellise: Yeah. The question is either about protein-creatinine ratio or PCR for Chlamydia and gonorrhoea. very confusing but I will answer both of them.

Bobby: Kidney function…

Dr Vincent Cornellise: Okay, kidney function. Yes. Everyone should at baseline have a urine protein-creatinine ratio and you check that every six months, so that is some standard protocol. Every six months, they have an eGFR and a urine protein-creatinine ratio, and guys who are, or people who are at particular risk of kidney issues, so older guys or people who had abnormal kidney function tests at baseline, those people I test more frequently. So, the standard is every six months, but more frequently, so every three months, if they have particular risks. And with the risks, so with renal function, and it is a good point. I would like to talk about renal function, but what I do generally when I see a patient for the first time, and I am working them up for PrEP, I try to work out their total cardiovascular risk, so obviously not for someone who is 18 because there is no point, but if someone is 60 and they want to start PrEP, you want to get an idea of their total cardiovascular risk. They do their blood pressure, cholesterol, sugar, all kit and caboodle because cardiovascular risk is reflected in renal risk. Case 2, 43 years old. His name is Steve. He only has sex with women, and he attends your clinic for travel vaccinations, as he is travelling to Thailand for his annual three-week holiday. Does Steve need to consider PrEP? Well, does he? So, however, these are interesting ones because, yeah, this is much more interesting that the last one, obviously because the last one was straightforward, but how do you broach the topic of high-risk behaviours that he might engage with while in Thailand, and it is a really important conversation to have with him because he might not realise that the HIV rate in Thailand is much higher than in Australia, and particularly amongst women, it is much higher in Thailand than it is in Australia. So, you need to have to think about how you might broach this. What I normally do with travellers is, you know, obviously you are talking about prevention, you are talking about immunisation, and I say, you know, what if you talk about, you know, having to wear a helmet when you are riding a motorcycle because the reality is, people are much more likely to have a traffic accident in Thailand than they are to get an STI. And just say, you know, we are talking about all of these preventive strategies, but can we have a quick chat about possible sexual risk and what we can do to protect you against sexually transmitted infections, including HIV, during your holidays. And most people I see, who are travelling and who are coming to see me, because I do a little bit of travel medicine every now and then, they are quite receptive to the idea of discussing sexual risk during travels. Again, it is just normalising it. So, what STI testing might you offer Steve? In his case, you know, at this point, he probably does not need a lot, but you have a look at the Australian STI management guidelines, and unless he reports any other recent risks, he probably does not need much, but if he is going to start PrEP, which is probably a good idea because he is going overseas, well, if he is planning to have sex overseas, you know, a country with high HIV prevalence, then you probably should consider starting PrEP just for his trip, and if he is going to start PrEP, then you need to do a HIV test and kidney function tests, where in Steve, otherwise you might not consider doing a HIV test because he is otherwise at low risk. Although you do not know because he might have gone, well, because this is his annual holiday, so he went last year as well, and he might not have had a HIV test since his trip last year.

1:23:54

So, you have a look at the criteria, and the medium-risk criteria for a heterosexual man is condomless intercourse with a heterosexual partner, not know to be HIV positive from a country with high HIV prevalence, and having multiple episodes of condomless intercourse, with or without sharing intravenous drug equipment. So, he is eligible because he is at medium risk of HIV. So, he can have PBS-funded PrEP. So, PBS-funded PrEP, just to reiterate, is for anyone who is at either medium or high risk of HIV. So, he is keen to commence PrEP and asks how long he needs to take it for, what do you say, well I would love to know what you say, but I what I am going to say is, so he obviously needs to start it seven days before, and he needs to take it for as long as he thinks he might have sex over there, and then for another 28 days after his last risk exposure. So, it is really quite similar to, for example, malaria prophylaxis with doxycycline, which is also about seven days before and four weeks after, although he may not need malaria prophylaxis, but I think it is a good analogy, oh sorry, he is not eligible, I have made a booboo. Well, he may not be eligible for PBS, so the reason he is not eligible is because he has not had a risk within the last three months, and this is exactly what I was talking about before at the start when I was talking about travellers. Travellers may not be eligible for PBS-funded PrEP because they do not have a recent HIV risk, but they can have a significant risk in the near future, so they may still need PrEP, so Steve may not be eligible for PBS-funded PrEP, but I would advise Steve that it would be a good idea to start PrEP, and he may want to self-import that, which means that he really needs to get organised because he needs to buy it online and wait for it to arrive in the mail. I have talked about this.

1:25:47

So, case study 3, unless you have any questions about case study 2.

Bobby: None, there was just someone saying that you got that wrong….. [Laughter]

Dr Vincent Cornellise: Thank you. I would like to be held accountable! Thanks a lot.

Bobby: [Laughter] _____ really. I think that you might be wrong.

Dr Vincent Cornellise: Thank you. I am very glad to see that you were all really paying very good attention. So, do we have time for case study 3.

Bobby: We have got four minutes or so. Probably not.

Dr Vincent Cornellise: Okay.

1:26:15

Bobby: Well, just a clarification question. What have you to find and where can you find out where are high-risk countries?

Dr Vincent Cornellise: That is a very good question. It is a difficult one to answer. Probably, your best source is the World Health Organisation, who reports on global HIV prevalence or the UN AIDS Organisation, sorry, a part of the United Nations. So, they have a website and they have annual reports, so you can find it there, but it is not easy to find.

Bobby: And that is really it. So, we have three minutes to go, I am not sure we will get through case study three. We could probably try if you want to.

Dr Vincent Cornellise: No worries, or unless anyone wants to flick a quick question now.

1:26:55

Bobby: Everyone will get access to all of the cases. So, there are four more cases, and I will put the slides out for everyone to access early next week. You will also get a recording of tonight’s webinar as well. There are some questions that will come up after the webinar tonight, just to answer your experience during the webinar, which we will feedback to ASHM as well.

Dr Vincent Cornellise: And before you finish up, can I just say that this Saturday is World AIDS Day, which I think it is great that the RACGP has put this on, you know, a couple of days before World AIDS Day, it is very poignant. World AIDS Day is a great opportunity for you to raise the prospect of HIV testing with your patients, so another lead-in, say hey, it is World Aids Day this week. When did you last have a HIV test?

Bobby: Yeah. A really good way to broach this conversation, which can be a prickly one to bring up in a consultation. So, thanks very much for coming in tonight, Vincent. It was really good. We are getting lots of great feedback through the questions here, which is great, so….

Dr Vincent Cornellise: Great.

Bobby: Everyone was really appreciative of your time and all of your information.

Dr Vincent Cornellise: Well, thanks, everyone for showing up tonight. I think it is, like I said I am very excited to see so many people interested in PrEP, and I would strongly encourage you to try and find your first patient that you are going to prescribe PrEP for. Make it you mission because once you have done it once, you will realise how super-easy it is, and then you will feel much more comfortable to keep doing it. So, thanks very much for your attention tonight.

Bobby: Thanks very much. Bye.