Editor’s Note:
With continuous progress in HIV treatment, the mortality rate has significantly decreased, and new infections have stabilized. However, there is still a gap from the 2020 targets set by the United Nations Programme on HIV/AIDS. To control new HIV infections, a comprehensive use of behavioral and biomedical methods, including antiviral drugs for pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), is crucial. This strategy aims to reduce HIV transmission and control new infections. The 19th European AIDS Conference (EACS 2023) was held in Warsaw, Poland, from October 18 to 20, 2023. At the conference, Professor Jean-Michel Molina from the University of Paris City, Saint Louis and Lariboisière Hospital, shared insights on the application and challenges of HIV PrEP and PEP.
Q1: Can you explain how antiretroviral drugs are used in both pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) for HIV prevention?
Prof. Molina: Right. So this is an important question because over the last couple of years, we’ve seen huge progress in terms of prevention of HIV infection. And we’ve learned that the drugs we use for the treatment of people with HIV infection can also be used for people who are not infected, but at risk for HIV acquisition. And that these drugs use either as PrEP, that means before exposure, or as PEP, that means after exposure, can actually prevent HIV acquisition with a very high effectiveness. It’s almost 100% effective when it’s taken as recommended. So it’s really a revolution in terms of HIV prevention to be able to use these drugs for people who are uninfected with HIV when they are not using condoms. It’s a very efficient way to stay uninfected.
Q2: What are some of the recent advances in PrEP and PEP therapy for HIV prevention, and how have they impacted treatment recommendations?
Prof. Molina: Right. So the initial PrEP regimen were based on oral PrEP, a combination of two drugs, ten of which are the same as the other drugs. and M -Pri Cetabine, FTC. Then we have increased the options for PrEP. The first option was to use PrEP on demand, so not as a daily regimen, but as a regimen to be taken before and after sex. And I know that in China, it’s also well used, as recommended by WHO for MSN. Then we have had other combination of drugs with TAF, FTC, drugs which is similar to TENOF -AVIA, but is called TENOF -AVIA alfino -mide. And more recently, we have long -acting drugs, injectable drugs, long -acting injectable antiretrovirals. The same we use again for treatment, capotegravir, which can be used for prevention. But for prevention, we use monotherapy with capotegravir, and it has been shown to be very effective also to prevent HIV acquisition in both men and women. So PREP is actually a way to use drugs for uninfected men or women at risk of HIV infection to prevent HIV acquisition.
Q3: What are the challenges and opportunities in managing substance use disorder in people with HIV, particularly in the context of PrEP and PEP?
Prof. Molina: So again, these drugs have been tested also to prevent HIV acquisition in IV drug users, but we have limited data. We have only a single trial, so we need additional information. That’s why according to the guidelines, they are restricted to the prevention of sexual transmission of HIV, sometimes not for IV drug transmission. And for IVD use, we know that there are a number of programs that are very useful and very efficient also to prevent HIV acquisitions like drug substitution therapy or programs we free and stir out syringes and needles, which are really important to enforce as well. So prevention is not about one tool, one magic billet. You have to combine the different tools we have, harm reduction strategies with IV drug users plus PREP. And for sexual transmission, you have the condoms plus PREP as well. And so what’s important is that people can use either one or both, but what we’re trying to achieve is that no one is using none of them.
Q4: Given the global surge in monkeypox virus infections, can you discuss the implications of this for individuals on PrEP and PEP?
Prof. Molina: Right. What’s good about PREP is that we actually were able to bring the clinic. People usually would not attend clinical visits or would not see a doctor. have, you know, capture, I would say, the high risk individual, high risk for HIV, for STIs, including Mpox. And so when the Mpox outbreak started in France, for example, it was easy to reach out to these people, which we knew were followed every three months for PrEP monitoring and to provide vaccine as early as possible. And so these people were well protected because, again, they are in a way taking care of themselves by using PrEP, you know, testing for STI, tasting for HIV.
Q5: In your experience, what strategies have been most effective in improving access to and adherence with PrEP and PEP among high-risk populations?
Prof. Molina: Well, here we need, you know, all the stakeholders to work together, especially to bring the community into the discussion. and the people themselves. So that’s key to make sure that everyone is on the same page and we can address and discuss the difficult questions.
Q6: So what is the outlook for DoxinPAP as a new tool for STI prevention? Can you explain a little bit its core mechanisms?
Prof. Molina: Right. Well, as you know for HIV, we’ve done a lot of studies, a lot of progress in HIV. Treatment and prevention. We’ve not done so well for STI treatment and prevention in the last 40 years. And so because, I would say, thanks to PrEP, we are now more aware of the issue of STIs. Not only in PrEP users, but in the general population. But PrEP users, because they are followed every three months for PrEP, they are a very good population to study STIs.
And that’s what happened with DoxinPAP. Because we’ve seen such a high rate of STIs in people on PrEP, we said we should do something about that. And since we don’t have vaccines yet available for bacterial STIs, we said why don’t we use STI post -exposure prophylaxis with Doxycycline? Because DoxinPAP has been used before in other diseases like Lyme disease, for example, as a post -exposure prophylaxis.
And so we started a study in 2015 and published the first results in 2018, showing a very strong reduction in STI incidence, in particular with Pramedia encephalus in MSM on PrEP using DoxyPAP. There was a limited impact on gonorrhea because gonorrhea is already resistant to tricycline in most countries.
So this was the first evidence and recently we have now confirmation by our colleagues in the US that the same Doxin regimen works very well. We’ve done similar studies again in France, a second study confirming all the symptoms of the disease. also this finding that this is a strategy that is very effective to reduce bacterial STI incidents in people at high risk.
So these are the short -term results. We have to be cautious in implementation because we don’t know the long -term consequences of using antibiotics. We know with antibiotics you are concerned about the increase in antibiotic resistance, of course. So we need to do more studies to understand the long -term issues that this strategy could have. And that’s why, again, this needs discussion with different stakeholders, with the community, who should be eligible for this strategy. It is very well -terrorated.
It’s a cheap strategy and people like it very much because with that they have much fewer STIs. But we, again, need to do more research to understand the long -term consequences of this strategy. So it’s a new strategy recently recommended by the US CDC. Also the EACS in Europe has issued new guidelines which are cautious about STI doxypep. So it’s moving ahead but you know it’s a relatively new strategy so we have to be still a bit cautious.
Q7: Thank you and about the CDC’s guideline would you like to make some comments on that?
Prof. Molina: Well, I think that the CDC guidelines are based on the study we conducted in France and the study conducted in the US as well. So it’s based on strong evidence of good effectiveness and good safety. What we still don’t know again are the long -term consequences of the strategy on the microbiome, on the STIs which may become more resistant to doxycycline. But what we know already is that syphilis and chlamydia are not able to become resistance to doxycycline as far as we know today. So indeed we need to monitor that and the interest of these new strategies is to foster research in STIs as well and to foster information about what’s the epidemiology of these STIs, their rate, the rate of drug resistance. So there are a lot of unknowns and with these new strategies maybe we are pushed to doing more studies looking at STIs in general.
