Prof. Jean-Michel Molina is a Head of Infectious Disease department at Saint-Louis Hospital in Paris. He is a Vice-Chair of European AIDS Society (EACS) guidelines panel on HIV treatment and a PI of pivotal trials: Ipergay and Prevenir. Thanks to these trials, in July 2019, WHO updated recommendations on oral pre-exposure prophylaxis as a part of HIV prevention.
In previous short videos Prof Molina introduced the basic facts about PrEP. In this conversation you will find more details about the importance of PrEP in controlling the HIV epidemic:
- Why do we need PrEP? Why aren't condoms enough to control the HIV epidemic? 00:08
- How do we know that the drop in diagnosed HIV cases in the Paris area is due to PrEP and not other factors? 02:04
- On-demand or daily: which PrEP regimen do users prefer and better adhere to? 03:28
- Is PrEP useful for the general population or should it only be targeted at the MSM population? 04:54
- How many people are using PrEP in France? 07:12
- Is the use of PrEP promoting a rise in other STIs? 08:08
- What are the side-effects of using PrEP? 11:23
- How are PrEP users monitored? By which healthcare professionals? 15:23
- How big is the issue of chemsex in France? 17:41
- What is the future of PrEP and PrEP delivery? Are there alternative and innovative options? Who will benefit most from these? 18:56
- What are the side effects of new PrEP delivery methods? 22:33
- What about the future of HIV treatment? Can we expect any new breakthroughs soon? 23:20
( Video transcript - scroll down to download )
UNIVADIS: Why do we need PrEP? Why aren't condoms enough to control the HIV epidemic?
PROF. JEAN-MICHEL MOLINA: We cannot control the epidemic just with condoms and the treatment of these people with HIV infection. And the reason for that is that a lot of people are transmitting infection at the early stages of HIV infection where the serological assay that we have are still negative. So that's what we call the window period. And during this period people may not know they are themselves infected, and that's why these people are transmitting HIV to their partners. And that's why we need to better protect the partners. So we know that to protect partners we have condoms, but that condoms are not always used for different reasons, because they are not convenient during sexual intercourse, because they can slip, they can break and people don't enjoy a sexual relationship with condoms for some of them. So we need additional tools. That's why we have pretty strong research on a vaccine, trying to find a vaccine for HIV, but so far the vaccine is not on the horizon today. And that's why we are fortunate to have another tool, which has shown to be very effective, which is PrEP. So now people to be protected have two options: to use PrEP or to use condoms. They can use both, obviously, but to be protected against HIV one or the other is good enough. And with this addition of PrEP we have shown in Australia, we have shown in the UK, and more recently in France, that you can have an impact on the epidemic for the first time.
UNIVADIS: How do we know that the drop in diagnosed HIV cases in the Paris area is due to PrEP and not other factors?
PROF. JEAN-MICHEL MOLINA: It's not PrEP alone. It's the combination of PrEP or it's the addition of PrEP in a setting where you already have a high use of condoms and you are already using treatment as prevention for people already infected, meaning that you treat very early people with HIV infection. So if you have a combination of these two, adding PrEP to that will have an impact. And the other explanation we can provide is that, for example, in France, or in Australia, the decline in new HIV diagnosis is only seen among those using PrEP, meaning MSM today, because PrEP is quite popular or being used among MSM, but not yet in other high risk groups. So in France, like in Australia, the decline in new HIV diagnosis is seen only among MSM at this point. The other proof of evidence is that we've used condoms and treatment as prevention for a couple of years already in the US, in France, in Australia and in Europe, and we have not seen an impact of the epidemic. And so in France it's in 2018, two years after PrEP approval, but we are starting to see a decline of new HIV diagnosis among MSM.
UNIVADIS: On-demand or daily: which PrEP regimen do users prefer and better adhere to?
PROF. JEAN-MICHEL MOLINA: We leave them the choice, and they find their own way. And actually, as I mentioned, it is not that different. And the WHO which recently endorsed also the on-demand PrEP for MSM, we want to make it simple for people. It's up to them. If they have sex with different partners every other day, they have to use daily, clearly. If it's one every week or once every two weeks, then maybe the on-demand regimen is more suitable for them, because they don't have to take a pill if they are not exposed to HIV. So it's really up to the people, and when we see them at every visit we discuss with them what's the best option for them. At the same time, they are also seeing and they have a discussion with a peer counselor on site, so they can discuss not with a physician but with one of their peers how to deal with these options of PrEP, condoms, what to do with the other sexually transmitted infections. So it's important that they not only see a doctor but they see also what we call peer counsellors on site to help them with adherence and to answer any questions they may have around the use of PrEP.
UNIVADIS: Is PrEP useful for the general population or should it only be targeted at the MSM population?
PROF. JEAN-MICHEL MOLINA: Because we have these good results among MSM, we need also to provide PrEP in other high-risk groups in France, like in the UK, like everywhere in Europe. It has taken a long time to make PrEP like a standard practice or a standard prevention method among MSM. And not all MSM still know about PrEP. So especially young MSM or those born abroad and coming to France for studies, to visit, we need to make everyone in the gay community aware of PrEP, because it's a community where we have a high rate of transmission of HIV. That's the same amount migrants from sub-Saharan Africa living in France. There is also a high rate of transmission in France. So we need to make them aware that we have a new tool to prevent HIV that is very effective, and we can now use the example of the gay community, that's very important. But now we need to work with communities, it's key to work with communities to explain what is PrEP, how to use it, and again, PrEP could not be used alone. PrEP is linked to testing for HIV, so we have to explain that HIV is still there in Europe, in the world. We are not done with the epidemic of HIV. People are still dying of AIDS today in our clinic. People are still getting AIDS. The rate of new HIV infection in France, we see every year 6,000 new HIV infections in France, for a country of 60 million people. So it's a lot of new infections. So we really need to do better. We don't have a vaccine, but we have PrEP today. So that's already very good. And so we should use it more largely, more widely, and we should work with the community to explain what is PrEP, and for that we need to rely on, involve the community, involve the people, so that they know about PrEP. So we need to increase the awareness of PrEP. We need the support of the government for that, but also we need the work of the community that's key.
UNIVADIS: How many people are using PrEP in France?
PROF. JEAN-MICHEL MOLINA: In France it's difficult to know how many people exactly are using PrEP, because we don't have a cohort in France because it's approved. And so therefore it's difficult to know how many people really are using PrEP. I think it's the same order of magnitude as in the UK potentially. We think in France potentially we have 20,000 people using PrEP. It's probably in the same range in the UK. Maybe a little bit higher. We don't have also exact numbers in the UK. But clearly in Europe, it's in France and in the UK where we have the highest number of people using PrEP, and we are hoping that in the future it's going to increase again, and that we will see a parallel decline in new diagnosis.
UNIVADIS: Is the use of PrEP promoting a rise in other STIs?
PROF. JEAN-MICHEL MOLINA: STIs, except HIV, I think have been increasing for the last ten years everywhere in the world. So far there was not a big issue, nobody was paying too much attention. Now, thanks to the progress in HIV and PrEP, STIs have become a priority in terms of research, in terms of monitoring. And again, thanks to PrEP we are monitoring and testing people for STIs much better than before. And we actually found that more than two-thirds of the STIs that we detect by frequent testing are asymptomatic STIs. So we can treat them earlier than before and prevent transmission to their partners. So we need to do much better on STIs. But for the last 50 years, there was almost no research in STIs. So now we have good tools for diagnosis, we need better options for prevention, so we need to promote research on vaccines for syphilis, gonorrhea, chlamydia. We have very good vaccines for hepatitis A and B, we need to use them. When we did the IPERGAY study we realized that 50% of these individuals had no protection against hepatitis A, which can be transmitted also during sexual intercourse, and there was a recent outbreak of hepatitis A among the gay community in Europe. So those in PrEP programs were vaccinated and were protected. So again, being involved in PrEP and being monitored on PrEP allows you to have access to other prevention treatment. For hepatitis B, that's the same thing. Hepatitis B can be transmitted sexually and only two-thirds of the population that we had in our PrEP program was protected.
So we need to increase the level of vaccines for protection, and again, we need to do more research on STI. Right now we are with ANRS developing in the Prevenir study, a large PrEP cohort of 3,000 people, three different programs on STIs. We have a program for hepatitis C eradication, because we see a lot of hepatitis C being transmitted. So we have a strategy of test and treat for hepatitis C in the cohort. And we have two other research programs on prevention of syphilis and chlamydia, and prevention of gonorrhea. We are trying to use cross protection from the meningococcal B vaccine to see whether we can use immune protection from the vaccine to gonorrhea. So there are some evidence that you might potentially have cross protection. So again, thanks to PrEP and thanks to this program with the support of the French agency for AIDs research, we have other research ongoing for STIs – which can benefit not only people at risk for HIV, but also all the other young individuals who are affected by STIs.
UNIVADIS: What are the side-effects of using PrEP?
PROF. JEAN-MICHEL MOLINA: You know, we are fortunate with PrEP because we are using two drugs, tenofovir disoproxil fumarate and emtricitabine, which are being still used for the treatment of HIV infection, and which have been used for the last 15 years. So we know these drugs very well, and the reason why these drugs are the cornerstone of antiretroviral therapy today for people with HIV infection is because they are very potent and very safe. And at the same time, that explains why also these drugs are available as generic today, because we have a long experience with them and they are off patent, at least in Europe, and very soon in the US as well. So only in the US they are still using the branded Truvada. The rest of the world is generic TDF FTC. And so we know that the safety, especially in young individuals is very good, very high. In our study, a minority, less than 0.5% of people had to discontinue PrEP because of adverse events. The most frequent adverse events are gastrointestinal adverse events, a little bit of diarrhea, nausea sometimes. So we tell people to take the drug with food to reduce the rate of adverse events, and usually with time it goes away. So I would say it's like any drug, you can have some GI disturbance. There are two other side effects that you need to monitor, but they are very rare. It's the renal safety of the drug. So you might get, in some people we have other comorbidities if you have diabetes, hypertension, if you take nephrotoxic drugs. You may increase the risk of renal toxicity. And so at some point you need to monitor creatinine level to measure your renal function. But we've done a number of studies with that and the renal safety is very, very good. So PrEP alone cannot injure your kidneys, it's if you have other comorbidities, other toxic drugs. So it's like the reason why you need to be monitored by a doctor. And it's also the benefit again to be in a PrEP program, you benefit from medical supervision. And a lot of people that we're seeing in the clinic today for PrEP, these people never saw a doctor before. So we can diagnose hypertension, we can diagnose other diseases, at the same time STI, we mentioned STIs, and that's the same thing for the use of drugs, of chemsex for example, and try to help people with that if they are using a lot of drugs. If I want to discuss the other safety issue is bone because these drugs on the long term can decrease a little bit what we call bone mineral density. But for men it's not really an issue because you don't get osteoporosis. The decline in bone mineral density is 1%. So it doesn't increase all the time, it's stabilized all the time. So it's really I think not an issue and that's nothing you need to monitor. So people don't have to be concerned about their bones when they are taking PrEP. And that's also the benefit of taking the drug on-demand, because on-demand you are less exposed to a daily pill, and so with fewer drug exposure the safety is better.
So in summary: the safety is not an issue, and people shouldn't be concerned about safety with PrEP. The safety is very, very high. I would say much higher than the pill for birth control, for example, because we have again a long, long experience with these two drugs for the treatment of HIV infection. And so the safety is very good.
UNIVADIS: How are PrEP users monitored? By which healthcare professionals?
PROF. JEAN-MICHEL MOLINA: You have to realize that PrEP is really a recent treatment strategy for prevention, and so not everyone is familiar with that. We need to teach PrEP in universities for young students. And we need to do a lot of teaching and make GPs and other healthcare professionals aware of PrEP. We have recent data from France showing that for the first time in Paris we have a decline in new HIV diagnosis. I hope will help people to feel comfortable with PrEP and providing and prescribing PrEP. So we need to make people more comfortable. It should be like the pill for birth control. In the 1970s there was a lot of skepticism, discussions about the pill for birth control. Now nobody is arguing that this is a method that this very effective and that women could use or not use. There are other potential tools to prevent pregnancies, but that's an option. PrEP, that's the same. People should be encouraged to still use condoms, but if they're not willing to use condoms, they can be protected against HIV, the reason why you need to be monitored by a doctor, but more and more in many countries nurses can do that as well and we have filed an application in France to allow nurses also to deliver PrEP. So that your people don't have to see a doctor every time, and the monitoring is very simple. You don't have to do that every three months, you could do that according to your baseline creatinine every six months, every year, just to make sure that everything is okay. And it's also the benefit, again, to be in a PrEP program, you benefit from medical supervision. And a lot of people that we're seeing in the clinic today for PrEP, these people never saw a doctor before. And so we can diagnose hypertension, we can diagnose other diseases, at the same time STI, we mentioned STIs, and that's the same thing for the use of drugs, of chemsex, for example, and try to help people with that if they are using a lot of drugs.
UNIVADIS: How big is the issue of chemsex in France?
PROF. JEAN-MICHEL MOLINA: Well, I think everywhere today people are using drugs more and more, unfortunately. So that's a big issue in the US, in Europe as well. So we know that it's not only people at risk of HIV, it's all young individuals going during the weekends to parties, discotheques etcetera. There are a lot of drugs on the market right now and people don't even know what kind of drugs they're using. So when they are seen during their PrEP visit we can open the discussion if they want to discuss that. If they are, you know, uncontrollable with drugs, like they are using too much drugs, we can ask them whether or not they want to see a specialist with drug addiction. So we have a nurse specialized to start the discussion and we are working with clinic, and so that's an emerging issue also. Because here we have a real safety issue with chemsex, or what we call chemsex, the use of drugs around sexual intercourse.
UNIVADIS: What is the future of PrEP and PrEP delivery? Are there alternative and innovative options? Who will benefit most from these?
PROF. JEAN-MICHEL MOLINA: Because we have now the evidence that giving these drugs used for the treatment of HIV infection for people at risk and to prevent HIV acquisition works very well, all the companies have developed research in PrEP to try to assess the efficacy of other drugs or other modes of delivery. So a number of other drugs are being tested right now to provide alternatives to tenofovir and emtricitabine, and the company who makes these drugs, Gilead, now has actually recently completed a study to show that another pro drug of tenofovir, tenofovir alafenamide, was as good as tenofovir in combination with FTC for PrEP in MSM.
And the safety of this drug might be a little bit higher in terms of renal toxicity. So in people who have renal impairment, for example, that's a very good option. The problem is that for Europe it's not generic yet because it's a new drug so the cost is higher. But for people who have renal failure, for example, and renal insufficiency and who want to use PrEP, they can use this option now. But I think more promising is the use of long-acting PrEP. Because one of the issues with PrEP that we are starting to see is that after some time people may be less adherent and less protected, therefore. So a number of companies are working on long-acting agents that you could inject, intramuscularly, for example, every three months. And so people can be protected for three months. Or what I think even more interesting is the use of implants, subcutaneous implants. The same implants that the companies have developed for contraception again. So the company, Merck, actually, who made these implants for contraception, is working on using the same implant to deliver drugs for prevention for PrEP. And they have shown recently at the Mexico conference last July that the drug they want to use in their implant for PrEP may be able to deliver drugs at a high enough level for almost a year. So then you may have an implant that could contain antiretrovirals, and these antiretrovirals can be even combined with a contraceptive. So for women, that would be great, for men as well, to have an implant to deliver PrEP, so you could have an implant for a year. There are also other options for women in Africa now, it's to use a ring, a vaginal ring that women put in their vagina for a month and which is able to deliver PrEP for a month, drugs, and so protect these women. The level of protection is lower than with oral pills because you don't have a distribution of the drug in every compartment because it has not reached the blood in high enough concentration, so it's a local protection. So protection is about 50%, but 50% is much better than zero percent. So again, this protection can be rolled out potentially in Africa as well.
UNIVADIS: What are the side effects of new PrEP delivery methods?
PROF. JEAN-MICHEL MOLINA: Well, some women complain of vaginal ulcers that might be related to the use of the rings, but overall the safety seems to be very good. So I think it's like contraception, very similar. You need to have multiple options for men and women. So you could have rings, pills, injectable agents, implants, and so then people can choose which one they want to use. And at some point they want to use pills and then switch to implants and then stop because they are no longer at risk. PrEP is not a strategy that you need to use for a lifetime. It's like the contraceptive pill: it's for a period of time when you are exposed either to pregnancy, and here to HIV.
UNIVADIS: What about the future of HIV treatment? Can we expect any new breakthroughs soon?
PROF. JEAN-MICHEL MOLINA: For treatment we have very potent drugs today. So on the horizon is rather again using long-acting injectable implants to avoid the use of pill every day. So there are strategies to use pills every week, maybe every month, injections every two months, that's coming very soon and people are very happy about that because when you have an injection every two months you forget about HIV and you don't feel like you are infected any more. So that's great for people. And implants as well. So the same kind of drugs, long-acting agents, can be used for treatment. But it's easier for PrEP right now, but it's coming for treatment, and the goal or the grail is to find a cure for HIV, and there are a lot of studies ongoing to find a cure to try to eradicate HIV from people already infected and so that they don't need to take drugs anymore.
Well, the side effects right now for people on treatment are very limited. Most people don't have any side effects. Most of them. So I think the breakthrough was really PrEP recently, and now we have to wait for – I think long-acting agents are going to be interesting for people, it's not a breakthrough as PrEP was because it's a real change in prevention. A breakthrough would be a vaccine, evidence for a vaccine efficacy, because we still need a vaccine. And a breakthrough would be – the next breakthrough we're waiting for a vaccine and a cure, that's what we need for HIV. To put it to an end we need a cure and a vaccine in addition. What we have today is pretty good, we can probably contain the epidemic, reduce the epidemic, that's already very nice and very important to do that, but in order to get rid of HIV, we need a cure and we need a vaccine.
Disclosures / Honoraria: MSD, Gilead, ViiV, Teva