Titre : 35 years of research on HIV: review and prospects
Intervenant : Jean-Michel MOLINA
AP-HP Groupe Hospitalier Saint Louis-Lariboisière, Paris
[Music] good morning or good afternoon everyone can you hear me hi uh thanks for joining online or uh here in the uh the amphitheater so it’s our pleasure for this fourth session of this uh infectious diseases seminar to welcome Jean Michelle Molina with whom we’ve had the privilege of interacting and collaborating with but we are not the only ones in in this room or in this Center Jean Michelle as you can see from his title slide has been around for a while doing HIV research too long maybe too long no no definitely not and has been very active I can tell you that in collaborations uh and so it’s our privilege to welcome him Jean Michelle mulina is a professor of infectious disease he’s a clinician and a researcher he’s the head of the uh infectious disease Department of St Louis and Hospital appp uh uh and and he’s well known in the field and as you see and this is why we invited him to he has a unique perspective on what has been happening in HIV research because he’s been around for 35 years uh and and changing a lot the Landscapes and he was also instrumental to a recent important change in in public health which was recommending prep uh which I think was a bold move from our minister of Health at the time and and so all of this uh we were very interested to have Jean Michelle’s uh um perspective on the spectrum of researches he has been con conducting uh so Jean Michelle thanks a lot for accepting our invitation and you have the floor uh for this presentation thanks thank you thank you very much Olivier it’s a pleasure to be here with you today and and it’s an an honor to address uh your your group your team and a number of people are know uh very well all the years and those online joining for today um you know it’s going to be a a special presentation today because I’m not going to talk about a specific topic and as you ask me Olivia to do I will try to um walk you through my career in term of U research in HIV and that’s why I entitled my talk 35 years of HIV research review and Prospect and I’ll spend a lot of time talking about review and maybe at the end uh and after my talk we could uh address the prospect so I’m a clinician I uh lead the department of infectious disease in Paris and I’m also linked to an inserm unit doing basic research in in virology so uh let’s go for about 40 minutes of presentation and then I be happy to have a discussion with you all uh so so when it started I uh thought I would uh show you this first publication in 1958 because that’s the year when I was born and uh it was interesting for me to see this publication from another Molina and you could see some resemblance because that’s my father actually uh who was a professor of neology in the University of J and he was uh you know uh in his career he has worked a lot on on TB and that’s interesting because as you will see I also do some research on TB uh and because the of the war my father then went to uh the University of claron feron and that’s where I did my medical studies at the University of claron feron uh was very happy here very nice University of Medicine um then I uh thought you know CL is a nice city but if you want to do research you better go to another place at least uh back in the uh 1970s and and then I uh decided to try to go to Paris for my residency and uh at the time I did my residency in Paris then I had a choice copero and Paris and then I decided Well let’s go to Paris um had great time initially and I did so my residency in Paris from 1981 to 1987 and at that time also I did some training at the pastor Institute on virology microbiology and epidemiology of infectious diseases and you have my first publication in English um uh during my last residency uh um stage in in in Paris uh on um crypto cocal infection in in a patient with AIDS how to make the diagnosis that was um in 1988 that my first uh publication in English then I went to uh to the US for my post doctoral Fellowship I started my PhD in Paris and then I completed the PHD in the pooc uh at uh the Deon Hospital linked to the Harvard Medical School for 2 and a half years and uh I met my mentor at that time uh was still active Professor Jerry grman and he’s an nematologist and he was one of the pioneer of HIV research in the US because initially a lot of hematologists actually were working on HIV and I learned about hematopoetic growth factors the interaction between HIV and the bone marrow how to look at the infection of proor cells also microfigures and the intera action between HIV and the cyto kindes and thanks to him you know I had my first paper in the New England Journal of Medicine in 1990 so more than 30 years ago on um the biology of U growth factors and we did a couple of publication uh during my time on looking at the interaction between HIV and the microf fases the cyto kindes and uh also looking at how to grow prot of cells from the bone marrow that’s a interesting assay to set up and then we looked at you know whether or not the bone marrow cells the prenal cells would be infected with HIV which is important when you think about cure strategy for HIV because if the prenal cells are infected that’s that’s an issue and we we couldn’t find any infection of these progenitor cells at that time then it was time to go back to Paris in the department of infectious disease at the St Louis hospital and my um Mentor here was Professor modai who has passed away unfortunately due to covid in his Department a couple of years ago and at that time during my um what’s called Clinica uh I was very busy with the clinical management of patients with AIDS and we had a lot of young people dying of AIDS at that time 1996 was before we had as you know um um very very active anti retral therapy available um many people had optimistic infection and we have very high morbidity and morality rates so at that time I was uh uh interested in looking at um opportunity infection in general and in particular on this one microsporidiosis which is a very broad broadly U very ous uh uh protool infection that usually gives you intestinal infection and diarrhea and I was really impressed by one of the patient I had at that time which who happened to be U former um the architect of the hital S Loui and these women actually was dying of intestinal microsporidiosis because of chronic diarrhea wasting weight loss Etc and I thought this was a very um at that time important infection to try to better understand and um you know we uh first published The U clinical features uh of this infection to try to understand what was the the problem and so uh with a group in uh opal Sal our colleague from the gastroenterology we uh identify the parasite uh for the first time and then try to define the clinical spectrum of the disease and then I set up with Professor Duran who also uh has passed away now um more than 10 years ago we set up a Research Unit within the university to uh address this topic of intestinal macros spuris because very few teams at that time were working on this infection and so we um improved the diagnosis of infection initially you had to perform judal biopsies and then we set up PCR assays to identify these um parasite uh looking at PCR first in D biopsy then in stool samples and we thought that this parasite was not um unique there was a many different subtypes of these parasite with different clinical spectrums and then we said well we have to uh I’m a clinician as you as you know and we were thinking about now we need to find a cure a treatment because there was no treatment for this parasite and we uh tested different drugs uh with different um uh clinical studies um with all the types of microsporidia we we could find very effective um response with um albendazol in randomized placeo control studies uh so that was one thing so with two different parasite we could um establish the effectiveness of albendazol but for the most uh frequent uh anoyone BN we couldn’t find any treatment so we had to try to uh test a number of different drugs and we did that in a phase two study where we tested you know 10 patients with one drug then you know if it didn’t work then we went to another drug until we could find an effective drug and the effective drug was fumagilin uh which is a a drug um that was found doing um uh literature review I did an extensive literature review to try to find drugs that could be appropriate to treat this disease and I went back to the 1960s where this drug uh was used for the treatment of anoyo or other type of microspores which were infected um uh a number of uh uh animals uh because it’s very common uh infection in animals and uh I can’t find the the word in English but this was a parasite which causes a lot of problems in agriculture and at that time they were using fumagilin to treat um these animals and it worked very well uh in human it has been also used for the treatment of intestinal amasis at that time before we had uh the drug we use today and I thought this is a drug that we might be interested to test in our patients and um I’m telling you the story because that’s interesting then I tried to see whether the drug was still being used for uh treatment in U Veterinary disease and in fact it was uh to treat honey bees because if honey bees are infected with microsporidia they do not produce hone anymore and that could be an issue and then I contacted the company sopi uh who was still making the drug to see whether we could make a partnership to try to see we whether we could have a drug that could be used for humans and you know when a drug is available and appropriate for animals for for bees it’s not exactly um immediate to use the same drug for for humans so we had to work with sopi and the French drug rry agency to make sure we had all the requirement uh to uh be able to test this drug in humans and when we did our um you know uh screening study screening trial this was the only drug which was magic because with all the other drugs you could to eradicate the um the parasite from from the stools and with that drug uh the first patient uh cleared the infection within two days and um you know he resumed um gain uh or he gain weight you know 10 kilos in about a month so that was kind of spectacular um I I forgot to mention that in the lab in vitro we replicate the the cycle of this parasite and we tested the drug in vitro as well and in vitro it worked very well that was that’s why we were encouraged to test it in humans then we we try a dose ranging study to to try to define the best dose to use and when the best dose was found then we uh they did the placebo control study that we published in the New England Journal in I think 2002 I think in this range um and the drug because the at that time because of the U availability of Highly active anti tral therapy um you know the we we had fewer patients with very Advanced imuno supression so we had fewer patients uh with HIV and so we included also all the imuno compromised patients in particular bone marrow transplant patients or patients with renal transplant in the study and the study was a Frank success you had 100% success in those receiving fumagilin and 0% success in those receiving place and when you switch the placebo to fuline then all clear the infection so there was a drug with 100% Effectiveness and the drug is still being used now in not anymore in patients with HIV because the the infection has disappeared today but is being used for uh the treatment of uh renal transplant recipients and so we did uh and even recently uh we we published in uh 3 years ago a review view of all the patients in France Reed the drug for treatment of intestinal microsporidiosis in in patients who have received uh a solid organ transplant and for this drug I had a patent and this patent U you know gave me some uh uh some Revenue which was uh interesting to uh to note uh because the the drug was very expensive uh but um so so uh but this is another story so we could discuss that later at the same time um I uh grew up in in the department and and became a professor of infectious disease and there was at about the same time that we had highly effective anti-al therapy available and then I started to be more interested in trying to improve what we had in terms of treatment for HIV infection so I became the head of the department in 2001 and I will and and that’s important I was really um involved in the network enrs the national AIDS research for um for uh AIDS and and heitis and I led within this agency the clinical trial group from uh 2005 20 2017 and it was very interesting to have um this interaction with other colleagues in other fields of medicine our colleagues from microbiology from pharmacology uh from social sciences from uh and also with the community of patients so a very uh useful and uh interaction and and then I became involved in clinical trials of anti- retrovirals and my first um uh trial was done actually with jenv Shen here whom you know very well and we started this collaboration with bordo so you can see that it’s a longl lasting collaboration we’ve won the trial that we started uh with jenv and her team with Valerie journo with whom we are working again 24 years later and we started the first trial the Albi trial just to mention that that was the first trial we we did at that time and and then we we tried another um combination and and I mention this combination because that was the first time we used um a combination of three drugs for the treatment of HIV infection in a single um in a single dose or in a single drug intake so once a day because at that time and we were I can’t find the yeah in the year 2000 um we we used a combination of three drugs with a huge number of pills two to three times even four times why not five times a day and at that time I had a collaboration with a A friend of mine who was working in the US in a in a small uh drug company called triangle which has been bought by the a bigger one Gilead today to test M triabin and M triabin is a drug um that we tested for the first time and because of this collaboration it was okay to uh test this drug in a French trial which we called Montana uh because it’s mono mono um combination once a day and at that time I had a lot of U discussion with u colleagues from uh the pharmacology uh field which were telling me well this is not going to work once a day is not going to work you need to give the drugs at least three times a day I say well let’s let’s try it because uh the there was no reason why uh it should be that way and I mentioned this study because that was again the first study done with a triple combination of anti-al therapy given once a day and this study was a very very uh good uh provided very nice results with a very high um rate of success and uh because of that there was a small uh pilot study uh because of that we um develop additional trials uh with a a much larger sample size uh still with a group of bordeau here called the aliz trial where we we did a non infity study and we uh looked at uh uh um many different um uh secondary end points which I’m not going to mention here today um another study I’d like to uh mention here is uh other trials are conducted with other colleagues from tulus uh on intermittent therapy because at that time we were thinking that maybe intermittent thy for HIV could be a solution to some of the Adverse Events of the drugs but we know that it’s not um useful at all and this was uh that study here I don’t know if you can see my arrow was a study we we did with my colleague EV Le on trying to uh to see whether we could U uh modulate the immune system by using interin in people with HIV trying to avoid the use or defer the use of of of drugs and we will come back to that at the end of my talk so many trials with with the NRS I mentioned those in in which I was involved in in particular the trio trial that was a a trial that I I designed uh but because I was the the head of the clinical trial group at NS I could not obviously lead all the trial uh but because of my relationship with the companies I told them this is a study a combination we should do in France um and and uh they agreed to work together uh with the NRS and to uh be able to to start this trial and I mentioned the the the role of the company of the industry because during that time I I’ve been uh interacting a lot with a number of drug companies which um provide me with nice collaboration and also a lot of knowledge because the the company is very rigorous when they do a trial they have to meet uh very clear guidelines to if they want to register their drugs and so there was a lot a great experience to work with companies and also with other colleagues other experts from different countries and you can see here that I’ve been um the principal investigators of a number of Trials uh looking at DDI or in particular at that time atav RAV which was one of the first Pi that was given once a day then real pivin which is a drug that is still being given today as you may know as a long acting drugs um also tenia alomide or uh trying to assess lower doors of uh of R return of year uh and more recently you know I’m still uh interacting with industry to uh address the effectiveness of uh uh integr Inhibitors derine a drug that uh is a new insty and uh um and because of this relationship there was a an opportunity for us when we want to design trials with the NRS to have the the U uh the relationship within the industry to have drugs available and and also as I said knowledge and so the last U publication I I had was this uh uh publication in the New England Journal last year on a new drug capsid inhibitor L A Cav in a trial of multi-drug resistant HIV 1 infection and you know I was the senior author on this international study and this was because of the trust of the company in uh you know the the work we we’ve done over the years um I also worked with another Network which is an important Network and uh as you can see having multiple collaboration is really critical um again because that enrich you in terms of uh of knowledge and and possibility of of doing um you know research so I’ve been involved in this important study that was called the start trial uh which was conducted at the same time as the temprano study that you know very well here and um because I was involved in this trial uh the the start trial which was a large international study to look at the best time to start art in people who are asymptomatic with HIV infection I I discussed with the head of the NRS at that time and I said well you know we’ve got to do a similar study in in France as well and I push him to you know approve the tempano study to make sure that the tempano study would not be deferred too too much and so uh this was an important study to uh change the guidelines uh the start trial and then I could you know in this trial um uh publish the uh um paper in the lens set about you know uh what are the who are the people who might benefit the most for early initiation of anti- retral therapy and you know I I learned a lot working with this uh Network although we have conference call usually at 10 p.m. uh once a month so that’s not so easy but uh that’s important to keep this collaboration uh at the same time during these years at at enrs I started to set up a collaboration with Brazil the director of the NS at that time asked me whether whether or not I would be interested to set up a collaboration with Brazil I said yes I’m interested in fact my uh sister-in-law is Brazilian and I said well that’s a great opportunity my neighbors were Brazilian as well and so I said well let’s go there and we started a very nice collaboration uh now it was like more than 10 years ago with my colleague batri Greenstein in the fuel Cruise foundation in Rio so I had the opportunity to go there multiple times and it happens that one of my U closest colleague in my team Natalie dcastro you had this her picture here is also uh from um Portuguese U ancestors or uh and so she speaks fluently Portuguese and and English and so that was also interesting to have someone with me to uh to bring in this collaboration and then we uh address uh there was also with the the group of jeen um um the issue of treatment of HIV in people Co infected with TB uh first study and then uh more recently a second study this time with Olivier and his group The reflect TB true trial a much larger study uh to look at uh uh the use of rra for the treatment of this Co infection and during these clinical trial usually you use the the data or the biobank to address other topics like the PK of the drugs or in particular and then I said well um using anti-al drugs is nice but we have now very potent and very good uh combination we we may not need to do any more research here it’s not that interesting as it was in the past and uh I thought then the the use of these same drugs for prevention could be probably uh interesting because we don’t have a vaccine to prevent HIV acquisition and what could we do to um to prevent infection and so we thought well maybe drugs could be used uh we had the example of the prevention of transmission of from women to their babies and uh we discussed with my colleague Jean buer um um first submission to to TOS in 2008 and the reason why I became interested in this topic was because I was asked uh by U uh my colleagues in Thailand to give a talk uh it was Mark LMA who invited me over to to go to to Bangkok to give a talk on you know what’s what’s going to be the future of HIV research and I thought well looking at the literature at that time prevention with drugs would be the best way to go and because of the experience we accumulated in the use of anti virals for treatment we said we we are well positioned to test this drug for prevention but we are not the only one and um we uh tried to find the best time to start our trial and we started only the study in 2012 because of we wanted to wait for the results of the first trial um done by my C in the in the US so we um present the the result of this trial in March of two 2015 and very soon after that uh the authorities in France in Europe and wh approved prep for the treatment for the prevention of HIV infection in the first study was done with by my colleague Bob Grant uh published in 2010 and we were waiting for the results of the study before we started our trial to make sure that our trial could be done uh in that study they uh use a daily um prep with one pel of tdf FC or a placebo in MSM at high risk of H HIV infection and what they found is after uh one year followup there was a 44% reduction of HIV incidents that was interesting but maybe not high enough that was actually below their expectation and they found out that the reason why maybe was not so good was because only 50% of the people had enough of it detected in the plasma and so we said maybe if we use um another design not giving uh prep every day but only at the time of sexual exposure we could have a better adherance and therefore a better Effectiveness so uh but we couldn’t do that until we knew that the results from the uh us trial were okay but not perfect and that there was room for improvement and so we did also a randomized bber control study in the same population of high-risk MSM in France and Canada to uh see whether tdf FC given before and after sex versus placebo would prevent HIV acquisition so that was the uh the scheme of how to use it with a loading dose of two pills not to mention that my colleague from the PK uh the PK expert not I’m not talking about the French PK expert but the US PK experts that told me this is not going to work no way that prep giv uh just uh uh before and after sex would prevent HIV acquisition well but in fact there was an adventure I would say this this trial I had to work with the community a lot so I had the experience working with the community for treatment and this time that was with the community for prevention because for prevention people don’t come to the hospital so you have to find them in night clubs as you can see I’m in the back trying to explain in gay clubs why are we were were willing to do a trial for prevention and why they should be enrolled in a placebo control study that was not granted and these are the the participants you see the picture in the middle at the end of the study we uh celebrate with the participant the the result of the trial which was made possible also by the involvement of the community leaders you have actor par and and A’s here and indeed the results were quite striking when you look at the incident in red in the placebo arm is was as high as um nearly 7% per year 9% in Paris and when you look at the blue line with tdf FC you can see Zero infection during the first 16 months so almost 100% Effectiveness and only two individual at the end um became infected because they stopped prep so the effectiveness was not anymore 44% it was 100% if you look at people taking the drugs and 86% in the intention to treat analysis so the results were were published in New England uh at the for the world day in uh in December of 2015 a few months after the um the public the presentation of the results at Croy and we also published a couple of months later the follow-up results because in u the follow-up study all participants could have access to uh to prep which was not available at that time in France and uh the effectiveness that’s why I mentioned this paper because we had an Effectiveness in a clinical trial of 9 7% of um you know reducing the incidence of HIV so that was very high um we had an editorial by um Anthony fouchi at that time in the New England saying that we have the tools to end the HIV epidemic we have to follow the results from the science we are very happy about that unfortunately at the same time uh it was in November of 2015 in Paris we had a terrorist attack in Paris very close to our our hospital it was just uh the restaurants where people used to go uh for dinner to have a break so actually the the the the people wondered and I had a couple of my colleagues from my team in the bars where the terrorist attack occurred and they had to use their Bell to make uh uh to try to save the lives of these people at that time and because of that I mentioned that because uh well we could not celebrate as we wanted the result of the study because of these attack and at that time the editor of the New England Journal of Medicine called me because we were in the time of you know publishing our results and he said well I know what’s going on in Paris is there a way you could help me to uh do a paper on how you are handling the tourist attack in the hospitals in Paris and that’s why we had this paper also from my colleagues in the Intensive Care Unit at in at the emergency room about that well anyway uh the the results were published in uh the wh 2015 guidelines the Ministry of Health approved prep as early as January of 2016 and then we um because of the large number of data we could publish the number of uh seary papers on the cost of these prophylaxis the issue of drug resistance the issue of toxicity um and we um made sure that uh as compared to to the daily use of prep the effectiveness of fundament was as good uh and we recently um conducted a large uh cord study uh in the Paris region trying to see whether when you implement prep you could have an impact on the new um infection at the population level so we did this large trial which showed that whether you use daily prep or on demand prep you have the same Effectiveness uh in terms of uh HIV incidents and um we within this trial looked also at a um rectile tissue biopsies as a mean to try to predict the effectiveness of prep regimen which is a difficult assay to set up and for that assay we collaborated with our colleague at the microbicide treatment Network in the U in the US to help us to set up the assay in in in Paris so this regimen of the called 211 ornament prep has been endorsed also by by wh and by other guidelines and today as you may know uh the the last report from uh apar showed that in November of 2023 more than 95,000 people have started prep in France and what’s nice is that uh from the most recent data from Sant puic France you could see that in red among men who have sex with men those who are using prep because 97% of people using prep in France today are men who have sex with men you can see a very nice decline of new infections new diagnoses I have to say 32% whereas in the other groups you see almost no change so we have the evidence that not only this prep regimen works at the individual level but it also works at a population level when you implement and you target the right people so we are trying now to improve this regimen and we’re working with jofra one of my young uh assistant who is now doing a pooc in in Chicago working on implementation science and we have this trial that we will start very soon we hope uh in collaboration with Thailand because we have kept the links with with Thailand which I mentioned earlier in my talk uh trying to assess a simpler regimen for Onan prep just one pel before and after and again with tftc t FC is not approved in France and again it is because the collaboration we have with Gilead that were able to get from Gilead the drugs to do the trial within the the prevenir trial which I mentioned we are also going to start a study using Cabra a long acting uh drug for prep which is U not available yet in France but the drug has been approved by the FDA in the US but in France not yet because probably of cost issues and we want to uh know whether in an open LEL study uh this drug really provides benefit to the patients and whether it could improve adherence to prep because we know it’s a critical uh issue for Effectiveness and finally we will start also in France and the UK and probably in August a study with another uh drug for prep L given only once every six months so with two injection per year you may prevent HIV acquisition so it’s almost like a vaccine and probably better than a vaccine to prevent HIV acquisition just a a word about covid because during the covid epidemic you know all these studies were ongoing uh and I was very busy as the head of the Department of infectious disease at s to take care of the patients and at the same time I was also the head became the head of the lar bazia hospital so I had two uh clinics to take care of so very busy to uh take care of the patients a lot of death again uh so I was not involved in a research Network on emergent in ious diseases or covid-19 because I was seen as probably only an HIV expert and not an expert in covid I think nobody was an expert but I was not therefore involved in in the network but we did our own research and uh just to mention that you know uh in March of 2020 we published um uh a small study we did in our unit to say that hydroxy chlorine didn’t work and the C well you know mentioned that because you only heard at that time what diu and his group were was were doing in marsill and you know these journalist said well there there are results from the team at the opal s Louis where they think hydr chlorin doesn’t work so um that was the the study we we so I contacted the lset the lanet said well we’re not interested because in the in in the L set we we usually don’t publish the letters um uh like that okay uh so we went to the medine Malad infix which is the French Journal of infectious disease and uh you know no evidence of the activity of hydroxy chlorine and I mentioned the reason why it didn’t work um and you know it was uh online march 2020 uh it was the most cited um publication and the most uh downloaded publication uh the the this review ever had and my colleague in the US which were writing the guidelines in the US for covid-19 told me well your your your data were important because uh these makers realize that hydrocyclin may not work but still a lot of people continue to use that drug although I didn’t want to be involved in any study uh with hydroxy chlorine well we also published another study about another drug REM desier I can spend a lot of time talking about that because at that time also France was the only country where remir was supposed to be not working and it was almost very difficult to use it despite the randomized crial trial done by the inside team which I mentioned earlier I knew the team I knew their work and they said no this they said well this drug provided benefit but in France people were reluctant about these drugs I don’t understand really why there was many studies done by the umrs at that time with mixed results but then we again looked at what we’ve done in our unit and we compared what we done in in our unit to what was done in other units where they didn’t use REM des and we found a very significant reduction of mortality so um well I’m going to uh skip that I’m going to finish now I know I’m late sorry for that uh to explain why I’m now uh doing research on uh sexually transmitted infections it was because during these studies in prep uh we had a lot of people uh with a high number of sexually transmitted infection and we said well uh we have to do something about that uh and because these people um like were quite captive because you see them every 3 months when they’re are on prep to detect HIV and STI and and people of the time were not anymore any longer concerned about HIV because they knew the prep was working very well they were concerned about the other STI and so well uh in the wake of the end of the eate trial we said the participants were so happy about the results they were ready to do anything that I would ask them to do and so I I told them would you agree to be enrolled now in another study uh to uh test an intervention to prevent STI and again looking at the literature on on STI because not to mention that I didn’t know anything about STI before I said well we there is a drug that seems appropriate to um uh to prevent STI it is doxy cycan and um I selected doxy cycling because of its activity against syphilis and camedia and also because it has been used for the preven of other infection like Lyme disease or lepos sporis and I thought well at least we know something about how to use it for prophylaxes uh these are a number of studies we’ve done uh during the uh prep studies to address the issue of of STI not only um bacterial STI but also viral STI um HPV hhv8 or um and others but I’m going to skip that uh and then we uh we did a trial with post exposure prophylaxis with doxy cycling to prevent STI in thegate trial which was published in um in 2018 a year after we got the results because we were concerned about how people would use these results so the trial was a simple design uh doxy cycling given after sexual intercourse uh because people were already using prep before so that was maybe too much or no p and what we found I’m going to was a reduction of the incidence of STI in blue with pep but what was striking was the effectiveness on camedia with a reduction of nearly 70% and 80% with syphilis no Effectiveness on on uh on gorea probably because of the high rate of gorea resistance which we know was already there so to confirm these results we uh presented this year at a larger study uh looking at doxycycline first and also the 4 C manb vaccine because we knew the effectiveness on gona was not good enough so we wanted to know whether a vaccine for menal disease which is very similar to gona could cross protect for gona and so the results very quickly uh doxic cycling we confirm the effectiveness on camedia and syphilis because we combine the end point here and you could see more than 80% reduction of clamidia and syphilis when people use doxycycline post exposure so after sexual intercour when they didn’t use a condom uh when you look separately at the two similar Effectiveness clamidia or syphilis gorea there was a small decline in incidents but not great 30% but still but unfortunately looking at the vaccine despite retrospective studies showing that the vaccine could provide a 30% reduction in um incidence of gorea in a randomized prospective study there was uh no effect that we could detect uh on the primary end point and on the other secondary end points so now we are trying to understand what was going on and we are working with immunologists to try to assess immune responses and to see whether we can identify a subgroup of people who have a immune response to the vaccine which may uh give protection for um goria and to do that uh what’s interesting is I’m going to work with the uh the person in Italy who actually invented the the beero vaccine and the group at GSK the GSK company is very interested about the the results and they have all the assays set up in their lab to to look at you know very um precise Immunology end point so we are setting up a collaboration with them to to look at that so in conclusion and sorry for being a bit long but uh I would say for the future perspective that are the advice I I could give you it’s very important to maintain uh large collaboration International collaboration are very uh key also working with networks is is critical network with within NS we have lucky enough in France to have agencies funding research on infectious disease and also working with the industry because you learn a lot working with the industry and you can have access early on to drugs that can be very useful when we did our study with prep with ten ftcs because all the work I’ve done before with Gilead that agreed to give me the drug for prep because at that time Gilead didn’t care at all about using their drugs for prep they wanted to use their drug for treatment it’s only because of the results of the studies that eventually now they are very interested to develop drugs for prep but initially they didn’t care about it we had a fight actually with them about the patent for using TD fftc for prep I can talk to you about that later if you want um so we are continuing research um on opportunistic infection on TB and TB with the the help of Olivier and his network uh trying to assess and reduce the mortality of TB menitis in many countries in in Brazil and um and and Africa we are starting uh again with Olivier a large multinational multicountry trial uh looking at derine versus um do R uh to treat initial infection with HIV I mentioned the study we are doing on prep with longing agents and also trying to do implementation research that is that’s really important now to to make this drug available to those who need it with STI uh I work with GSK now in a new vaccine for gonore infection which seems very promising so let’s wait for the result this trial has fully enrolled now we are you know very uh eager to see the results and I and I think the next really Frontier in HIV research is the remission The Cure of HIV and now uh back again to my former colleague Eve leevy and rodolph who is here trying to see whether we can you know design uh a study to uh to try to induce HIV remission so let’s hope this is going to work uh develop new partnership is clearly very important I mentioned the new partnership we’re going to develop with GSK now on better understanding the immune response to the vaccine and I think what’s great also is is to have in your group Young new and and Brant investigators who can help you to to do all this work because all this work is not my work is the work with a large number of people uh I’m lucky enough to have a large group also in my department and uh I mention not only nurses but also not only doctors but also nurses um research assistant so uh the work that I presented here to you today is not my own work it’s the work of a very large team and thank you for my for your attention and I close here with the different partners we had over the years and um The Gates Foundation for example um agreed to fund for the first time a study in Europe uh on prep that that was also the reason why we were able to conduct the study so thanks very much for uh your [Applause] [Music] attention