• 08 Dec 2020
  • 20 min
  • 08 Dec 2020
  • 20 min

Dhineli Perera talks to medical epidemiologist and public health physician Andrew Grulich about the successful story of pre-exposure prophylaxis for HIV infection in Australia and what lies ahead. Read the full article in Australian Prescriber.


Welcome to the Australian Prescriber Podcast. Australian Prescriber, independent, peer-reviewed and free.

I'm Dhineli Perera your host for this episode. And it's a pleasure to be speaking to Professor Andrew Grulich. Andrew is the head of the HIV Epidemiology and Prevention Program at the Kirby Institute at the University of New South Wales. Andrew writes about the successful story of pre-exposure prophylaxis in Australia and the challenges that remain ahead. Andrew, welcome to the program.

Thank you Dhineli. Happy to be here.

Great. So Andrew, would you mind refreshing us all on what exactly pre-exposure prophylaxis is? So for the rest of you, that's also known as PrEP. How exactly does it work and how does it fit into the scheme of things?

Sure. So look, essentially PrEP has been quite a revolution in the way we prevent HIV around the world but most definitively in gay and bisexual men. It's essentially a reduced combination of antiretroviral drugs that are used to treat people with HIV. So it's co-formulated tenofovir and emtricitabine. People take one tablet once a day and having it in the bloodstream at the time of exposure prevents HIV infection.

Right. Okay. So it's using the same drugs that would use to treat HIV, but at a lower dose? Would that be right?

Not so much a lower dose, but a smaller number of drugs. So typically treatment of HIV will be based on at least three antiretroviral drugs. This is based on a combination of two antiretroviral drugs in a single tablet.

Right? Okay. So the introduction of PrEP in Australia has been quite a success story. From your article we've seen a really rapid decline in new HIV diagnoses which is an excellent outcome. Something in the order of 20% I believe. Can you tell us what the drivers and enablers were that helped with this?

Sure. Would be happy to. I'd first say that 20% is the overall reduction. It's more like a 30% reduction in gay and bisexual men and even larger reductions in some subgroups, particularly Australian-born gay and bisexual men. So these have been unprecedented drops and in parts of Australia, at least we're seeing levels of HIV notification that are lower than has been seen since the beginning of the epidemic. So what's enabled the introduction? I think it was very helpful that we introduced PrEP in a number of large-scale demonstration projects around Australia in almost every state and territory of Australia in fact, which enabled us to do it in a research setting.

The things that have enabled it are clearly our national health system. In many parts of the world that have introduced PrEP early, such as the US, have been really impeded by the fact that people at risk haven't been able to get it but our health system enables people to get it through the PBS now. In much of Australia, it's been facilitated by the existence of sexual health clinics, which specialise in this, but we're really at a stage in the rollout now that we want it to go way beyond sexual health clinics. Every GP in Australia should be able to prescribe PrEP for a person at risk.

Okay, excellent. So just out of interest, has that same success been seen or replicated anywhere else in the world?

There have been successes in parts of the US, but they tend to be small cities rather than large areas, certainly not nationwide. Australia has taken up PrEP probably more enthusiastically than almost anywhere in the world.

So given that this is something that we would like to see more in general practice, how do we define an at-risk individual? Is there certain criteria that needs to be met? And if listeners want to know more about this definition, where should they go?

Sure. So look, the main thing about risk and HIV in Australia is that HIV is mostly concentrated still in gay and bisexual men. So take-up thus far has been very predominantly in that population. In gay and bisexual men, essentially the definition of a person at risk is simply a person who may be exposed to HIV. And so in the setting of gay and bisexual men, that's a man having anal sexual intercourse who might not always be using condoms. They may come to a doctor saying that, or a doctor may need to elicit that information.

So we do need doctors who are comfortable talking to their clients about sex. And it's also worth saying that the news about PrEP is quite broadly disseminated amongst gay men, but not all gay men are on it yet. So it may also be the case that a person comes forward saying that they've managed condom use reasonably well thus far, but they want to be on PrEP because they hear it offers good protection, even if they're not currently having condomless sex. So this is such an effective intervention, really very close to 100% effective in people who take it one pill once a day. A person at risk who wants PrEP should not be denied PrEP.

Oh, okay. That's actually really worthwhile knowing then that an at-risk individual doesn't have to be someone that is not complying with condom usage. It just really has to be someone that fits into the population you've described and is willing to take it.

That's absolutely correct. And so if a doctor assesses that a person is at medium to high risk, then that person is eligible for PrEP. It's probably worth me saying that there would be some heterosexual people who would qualify for PrEP in Australia. If the doctor believes that they're in a higher risk setting. So for example, a woman who's having sex with a bisexual partner and doesn't know much about that partner because the prevalence of HIV’s so much higher in homosexual and bisexual men in Australia, that could be a condition where the doctor may feel PrEP is indicated.

Also in people going on holidays to settings where the prevalence of HIV is higher and where they believe they may be having sex on holidays, a short course of PrEP to cover the period while they're away may also be indicated. It's not just gay and bisexual men, but it is mostly targeted at that population.

Okay. And where did you say people need to go to get more information?

Yeah. I think the best place to go is the website of the Australasian Society for HIV Medicine or ASHM. A-S-H-M. If people google, ASHM PrEP, they will find not only extremely detailed guidelines, but some really useful, easy-to-follow single-page instructions for how to prescribe PrEP. And a key message is really that prescribing PrEP is really easy. It's not a difficult or complicated thing.

Okay. Well that leads me neatly into my next question in that your article describes it as a three-monthly testing and prescription cycle. Are there clear instructions perhaps available on the PBS website or anywhere else for GPs to use regarding this cycle? Like for example, what needs to be tested, what action needs to be taken based on these test results and algorithm perhaps?

Yes, absolutely. I think the most user-friendly ones that I find are on the ASHM, A-S-H-M website. When people just google ASHM PrEP, it's all laid out there. But essentially a person just needs to be tested at baseline for HIV, because clearly this cannot be given in HIV-positive people. Tested then quarterly for HIV and sexually transmitted infections. And every six months for kidney function. There is a rare kidney toxicity of this medication. It's usually mild and reversible, but it is contraindicated in people with severe renal impairment.

Okay. So that's not very involved tests then, it's just basically two main blood tests?

Not at all. And the only other important thing is amongst those STIs you test for at least at baseline should be hepatitis B. And the reason for that is that these drugs also have activity against hepatitis B. So if a person has chronic hepatitis B and goes on these drugs, they need to stay on these drugs because when they're stopped suddenly you can get a flare of hepatitis because you're withdrawing treatment. And that is a little complex and for that reason, we often recommend that a specialist be consulted if you're thinking about prescribing PrEP to a person with chronic hepatitis B infection.

Okay. So for those patients that do have it, did you say referral or to-

Yeah. Referral to either a sexual health physician because sexual health physicians prescribed PrEP a lot or to a liver specialist, but probably in this setting the sexual health position is going to be more familiar with it.

Okay, great. So I won't go into asking you how does it precipitate the flare because it actually sounds like it is more complicated.

Yeah, sure. It's essentially, it's just that these drugs treat hepatitis. And so if they're stopped, the hepatitis comes back and it can come back very quickly causing clinical hepatitis. Although in fact, the more experience globally we have with this is that a serious flare of hepatitis after stopping is actually pretty rare.

Excellent. So is there more than one option available, Andrew, for PrEP or is it just a one size fits all kind of situation?

When PrEP was first introduced in 2018, we said it was one option. That's one pill once a day. And I should say with this, that for gay men, it's actually quite forgiving in that regimen that even if a person missed a couple of tablets a week, they would still be well-protected provided they took it on the other days. That's for gay men. In women in fact, so for vaginal protection, really strict adherence daily is required.

Why is that the case?

Well, it's just got to do with the distribution of the drug around the body. It's just high levels of these drugs are found in rectal tissues, whereas much lower levels of the drugs get to the vagina. There will very soon be other alternatives for women, which is good news because strict daily adherence is not easy for anybody including injectable drugs. They're not available yet in Australia, but injectable cabotegravir has recently been shown to be quite effective in preventing HIV in both men and women. That's for the future however.

For the moment there is one other option. And because of the concentration of this drug, it is better in rectal than vaginal tissues, this is only an option for gay and bisexual men for protection against anal sex. And that is event-based dosing, sometimes called on-demand dosing, which is a three-day course of four pills. So a loading dose of two pills taken two to 24 hours before sexual intercourse and then one pill taken the next day. And then one the day after that. Sounds complicated, but actually people do get used to this regimen. If, for example, they're the sort of person who's only ever at risk every week or two weeks or month, they don't want to take a pill every day, in that on-demand regimen it means taking a lot less pills. As long as people take the pills properly it is virtually equally effective as taking daily PrEP.

So Andrew, I'm guessing that one frequently asked question you must get is, does PrEP result in lower use of condoms and therefore a higher transmission of other STIs?

So certainly in populations where PrEP has been taken up quickly, including in Australia, we do see a decline in regular condom use in the gay men who are taking PrEP. And this sort of phenomenon has been seen before. When the oral contraceptive pill was first introduced, women who had previously relied on condoms for pregnancy protection often started using condoms a lot less than they did previously so it's not unexpected. But the second part of your question about whether sexually transmitted infections go up is complex because testing for sexually transmitted infections is part of the package of PrEP. So people are tested every quarter for STIs in their throat with a throat swab and anal swab, which often can be done in many things is done by the participant as a self-collected swab, and a urine test for chlamydia and gonorrhoea and as well as blood for syphilis.

And those SDIs are often asymptomatic and don't present. But if we test for them quarterly, we pick them up quickly, treat them if they’re there and therefore decreasing the prevalence. So what we are seeing in most populations is that STI rates don't go up, they stay roughly constant. They certainly don't go away either, but there's no evidence at a population level that STI rates actually increase.

Great. So it's just sort of resulting in closer scrutiny I guess.

Yeah. It's a balance of some increase in risk because people aren't using condoms, but decreases in incidence of STI is related to treatment and therefore decreased onward transmission of existing STIs.

Excellent. So can you tell us a bit about the concept you've mentioned in your article called treatment as prevention?

Treatment as prevention is basically another absolutely critical pillar of HIV prevention at the population level. So it's become clear over the last five years or so that HIV-positive people receiving antiretroviral therapy who are on effective treatment and when I say effective, that means they've got undetectable HIV viral load, those people cannot transmit HIV. And so the effective treatment of HIV is a great way of preventing HIV onwards transmission, because the HIV is at so low levels in their body after after being treated that they can't pass it on. So it's another pillar of the way we prevent HIV in this day and age.

Condoms are the third pillar really because condoms are still a great way for individuals to protect themselves against HIV.

And I guess it is a newer sort of concept in this field, but is it one that there is more research being done on like using it as a preventative method?

Well, so the research about whether it works for an individual is very much in, in both heterosexuals and in gay men, and some of that data from gay men come from studies we've done here in Australia. It's very clear that once you've got undetectable viral load you don't transmit. Now how effective that is at a population level in preventing spread, depends on how high your testing rate is. Because many people who become HIV-infected don't know they are positive because they've had very mild symptoms and they don't get tested. So that person, until they get on treatment, will be quite highly infectious because they have higher viral load.

So a lot of our population-level prevention strategies are about ensuring anybody who might be HIV-infected gets a test for HIV. And if we've got GPs from around Australia who are still listening at this stage, if there's one really important thing for them to know is people should be tested for HIV with a very low threshold because once you diagnose a person it's great for their personal health to be on the treatment. So these days they'll have an almost normal life expectancy provided they're treated early and they'll also not be able to transmit onwards. So testing, testing, testing is so important.

Excellent. So Andrew, I was fascinated to read in your article that men who have sex with men who were born overseas now account for about 50% of new diagnoses. And the reasons for this are obviously multifactorial. In your opinion, what are the most important reasons and are there any plans in place to help address it?

So our approaches to preventing HIV are often very focused in the gay community in Australia. So educating gay and bisexual men that are at risk, how to get tested, how to get PrEP. All of those things are sort of, if you like, situated in the Australian culture. Now a lot of young overseas-born people, and a lot of these are recently arrived people, come from much more socially conservative backgrounds and the most common areas in which these overseas-born people with HIV are coming from are South-East and East Asian countries and also some South American countries. So typically these are cultures where they've had very little sex education and often quite stigmatised attitudes towards homosexuality.

So they arrive in Australia without the means if you like to access HIV prevention. They often arrive here without access to Medicare as well. So if they feel they can't get tested and get effective treatment, they'll often be inhibited from presenting. And it is important for doctors to know that if they are aware of any patients like that, who aren't eligible for Medicare, then in most states and territories, they can refer those patients to sexual health centres where health care is absolutely free. The person can receive free testing, free health care and free referrals to get PrEP, not on the PBS, but through personal importation.

Fantastic. I wasn't aware of that either. So that's really good to know and really important information to get out there I think.

Very important. It's not widely enough known and particularly, I think among young people who haven't been in Australia for very long, and we have of course enormous populations arriving in Australia, well we have until recently for, to be students, whether it's university or trade students, very large populations who we need to engage in sexual health education.

Yeah. Excellent. So Andrew finally, how likely do you think it is that we will see the elimination of HIV in our lifetime in Australia?

So you'd have to say that it is theoretically possible that we could eliminate HIV because PrEP is virtually 100% effective in people who take it. Condoms are virtually 100% protective in people who use them and treatment as prevention is virtually a hundred percent effective in people on long-term antiretroviral therapy. So with those tools, it is theoretically possible.

The challenge is to get high enough levels of uptake, and that's got to be about education of people at risk, but also the situation of some of these diseases now in populations who aren't as well engaged. And we've talked about the overseas-born, there's also emerging evidence which tends to show us that the reductions in HIV we are seeing are concentrated in the inner cities. And once you're out of the inner cities, possibly where there's less access to gay community, or there's more stigma associated with homosexuality, that we're not seeing those reductions. So I would say it is theoretically possible, but we've got some fairly major health disparities to address to get there.

Fascinating. Thank you so much, Andrew. That was really interesting. And for those of you that are interested in this particular interview or this podcast, there is further articles on HIV in the December issue of the Australian Prescriber. So definitely jump on once it's available and make sure that you have a read of both Andrew's editorial and the other article that has been published in the same edition. So thank you once again Andrew for joining us today.

Thanks Dhineli, I really enjoyed it.


The views of the hosts and guests on the podcast are their own and may not represent Australian Prescriber or NPS MedicineWise. I'm Dhineli Perera and thanks for joining us on the Australian Prescriber Podcast.