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hey guys R derazi here and I wanted to share with you um a little bit about this meeting annual meeting that we’re having and what you’ll often find at conferences is what’s called a poster session and so this is an opportunity for researchers also known as investigators have an opportunity to share their work that they’ve been working on um via a poster as you can see and it’s like a summary of of everything that they’ve been doing often times there’s only a limited number of speakers that can speak at conference or a meeting like this one and share their their research so this gives an opportunity for um some of the other projects to also have some time to Showcase their work and what’s really cool is that often times like during this poster session the person who’s been working on it will be next to their poster available ready to explain everything that they’ve been doing if you have any questions you can kind of like have a conversation with them which is cool so you get that one-on-one time as opposed to just seeing someone like on a stage talking about their uh research okay so let’s go check it out I’m going to see if I can grab some people and like force them into um being on camera with me before we jump into the rest of the video I wanted to quickly let you know that I’ll be talking to six different people apologies for the relatively poor video quality I didn’t have my camera with me my DSLR I just had my iPhone so I was using that and the audio isn’t great either but that’s kind of virtue of the fact that we’re we were in a pretty like loud place if you watch the people that I’m interviewing you can see that they are actively translating the scientific language that they’re used to using into into more understandable language for someone like me and this is not an easy task I’m sure it’s very difficult to do on the spot for some of the investigators that I’m going to be talking to that happen to be part of the hope collaboratory we’re going to be talking about three distinct areas in the block lock stop model for reaching an HIV cure if you’re unfamiliar with what this is I posted a quick video explainer um of block lock stop which is the focus of the hope collaboratory and I’ll put a card up here so you can watch that too if you want a little backstory to what we’re talking about in this video it might help you understand things this is an opportunity to actually get to talk to someone who is working on I don’t know you call it an experiment what do you call this in general yeah it’s a a set of experiments I mean this is just a method that I’ve been working on um to look at a specific modification on DNA okay so I would call this like a methods poster a methods poster yeah this not a full like clinical gotcha okay and so I’m here with Alina today and she’s going to tell us a little bit about the poster that she brought here to the meeting so I’m alinaa and I’m a post in Dr do lab um and this is a method that I’ve been working on recently to look at a specific type of modification to DNA called DNA methyl one of the focuses of Hope is how epigenetics can put the virus into deep latency um there are two main modifications to DNA at the histone level and onto the DNA itself so would that be the the the lock part of the yes lock lock stop Yes okay so we find that in herbs um which is what doug FOC herbs and would you would you mind um explaining to them really quick what that is a lot of people have never heard of it there are endogenous retroviruses called herbs that are in our genome um there are modifications to the DNA that really silences them and represses them so that they’re not being expressed so they were once like active viruses were having an impact on you and me but then I mean in the past and then eventually just became inert basically in our in our genome and they’re there but they’re not really having an impact on us anymore yeah and so that’s one of the methods or the potential mechanisms that we’re looking at um potentially to silence HIV yeah this method is called targeted end and maatic methylation sequency for the provirus and so we wanted to capture the virus’s DNA methylation so methylation happens on these nucleotides called cytosines when they’re next to a Guan typically so we call those cpgs I I was going to ask if you could like simplify what methylation is or what basically your DNA is marked okay by these methylation marks okay and that will turn genes on or off okay yeah so it marks the DNA flipping it on or off exactly got it that’s great and so when methylation is there it shuts off oh great okay so um and so that’s part of making it endogenous yeah okay making it silence silence in the past a lot of the experiments that we’ve done to look at the role of DNA methylation for viral transcription has been done in cell lines or models um that we grow in the lab of of cd4t cells or sometimes monic cell lines um that have HIV integrated into un name mhm when you have an inflammatory response uh you can put in certain cyes on these cell lines and then HIV will reactivate and transp so we’ve been using this as a model for the reservoir latency can you speak to what cyto kindes are they’re like it basically causes an inflammatory response injury because I was going to say I heard of that during covid yeah they talked about cyto Kine storms yes yes yes okay so like information is good and bad right yeah so when it’s balanced when it’s balanced it’s it creates a response that will Target bacteria viruses yeah uh too much inflammation or for inflammation for too long is detrimental to your body yeah so in case of Co you had these overwhelming Ms of cyto Kines in your body and yeah people would die from the C St okay so basically what we did was we created this method to look at DNA methylation first we started in cell lines and so basically the we created these molecular probes that pull out the HIV DNA from the celline DNA because HIV is so rare right in all of our cells we have to find a way to Target it and capture it um and then from there we converted it using of different enzymes um which is this is pretty complicated it’s fine I I need to explain the yeah yeah just the overview so HIV is not prevalent in all of our cells all in our body it’s in specific areas yeah so we created these probes that look for the actual sequence of the HIV virus and pull it out of the host all of your H DNA and then we looked at the cpg methylation across all of essentially the entire virus so before previous methods would very like were very damaging to the actual DNA itself so when we would try and sequence the virus you would get maybe like a little bit here little bit there and nothing else so it was really hard to captured all of it across entire body and to clarify you’re taking cells out and analyzing that DNA not while it’s in the body yeah so these so you’re not like damaging DNA in someone’s body and like going okay yeah so we took so this is in cell lines but then we took people’s blood cells and then we took the DNA out of those blood cells and we did the same yeah in other words it’s safe it’s safe for everyone it’s safe for you like same thing is just when in the doctor and your getting your blood dra exactly yeah cool this might be a little bit too in depth but so there’s like these cpg marks or methylation that like this is the viral sequence okay this is at the five Prime LTR so this is Upstream of the virus this is the uh virus when it’s resting when you activate it with inflammatory like a inflammatory signal this usually turns on uh HIV transcription yeah you see that these marks go away so this basically says that maybe there is an irregulary role for DNA marks in this region so these Mar markers kind of switch off they switch off okay and get oh yeah that’s what I was going to clarify DNA transcription is the process of making new RNA RNA that goes throughout the body finds another cell to inhabit and starts the process all over again so this this is specifically focused on the replication uh the transcription part yeah shutting off transcription turning off transcription okay so that the little Factory can can’t continue to create new RNA which is like I said the little soldiers that go out and infect other C that was great no yeah we have a great General overview of of what’s going on with some some details so I think that’s awesome thank you Elena appreciate it all right everyone so we are here at another poster this is Ruben’s tavora and um you work with the Valente lab Su Susanna Valente is one of the pis um and he’s going to explain his poster to us now hey guys how’s it going yeah yes I’m rubben really excited to give you a tour of my little uh poster um as you know uh hope is All About the Block lock and stop approach um and my poster really is about using two different drugs in combination in an attempt to hopefully one day reach the functional cure of HIV basically the the the the the main premise is that we want to actually use these drugs which are transcription Inhibitors right so they’re preventing the virus from ever being able to replicate itself uh and we want to use these drugs mainly in combination with art okay uh the beauty of these drugs though is that uh hopefully one day if you take them for long enough you might be able to stop taking the transcription hibitor as well as stop taking art and you would not have a return of viral expression so you basically be functional cured at that stage that’s undetectable essentially that’s exactly right so You’ stay undetect even without taking any medication we have some uh proof that that’s the that you can do that in in cell cultur so you can actually use cells and we can use these drugs and show that even after you you you you stop uh putting these drugs in the cells that the cells never go back to producing uh uh HIV uh uh proteins and and and genes right now uh the the the the two drugs that we have and the drugs I’ve been talking about one of them is spirolactone uh and the other one is DCA which you may be uh familiar with um so spring lactone uh is really exciting because it’s already an FDA approved drug so so people take it uh for heart disease uh and they take it for a wide range of conditions so we know it’s a very safe drug uh so it’s really easy for us to take that drug and actually try it in people because there’s already uh the safety and there’s already the all the different phases of approval have already gone through so very exciting and then these CA uh which is another transcription inhibitor has not undergone the FDA approval yet but we have some really uh uh important data in cells and also in a mouse and and in monkeys that show that DCA is also really really a powerful drug uh at stopping uh HIV from being able to to transcribe itself I’m not going to bore you with the with the background uh in terms of what these drugs have done but uh what I will say is that the main take-home message the the main point of my poster is that if you use DCA in combination with SP so two different D drugs that are both transcription Inhibitors but that do that in different ways okay so so SP is going to prevent uh the virus from start the transcription and then DCA is going to prevent the the the virus from being able to keep going okay uh so to reiterate transcription is the cell’s Machinery replicating itself so that it can go on and infect other cells right exactly so so basically the the analogy I like to give uh is that if you think of proteins being French toast or a food they really like uh then uh and you think about a recipe right so you you need a recipe to make whatever food you’re you’re you’re interested in right so if you have a a recipe which would be your DNA so so imagine your well grandmother’s home and she might make really great French toast so uh maybe she has her recipe book with everything that’s in there uh well in that case that’s kind of like your DNA right it’s got all the instructions to all the different recipes that you may ever want to know uh but you know if you’re interested in making that French toast yourself you’re not just going to take all of that uh you know of that book that your grandmother holds you’re going to make a copy of that of that particular page that you’re interested in and that’s what transcription is it’s basically making a copy of your DNA into uh a paper that you can take home and make the protein which in this case uh is RNA right so RNA is the copy that you’re taking so when we talk about transcription we’re just basically talking about uh the the the the the production of RNA from DNA that that’s that’s the I think the best way I can explain it so these drugs are effectively preventing the virus from doing that they’re preventing the virus from ever becoming a protein from ever becoming itself because you’re preventing the copy of the the the main cookbook from ever uh being able to be produced basically it’s like you have no pen okay so if you have no pen you have no pen so you’re not going to be able to to then make that copy uh to take home and then make the your French toast basically uh but again uh these drugs are doing that in two different ways which is why we think that if we use that in combination uh it’s going to be uh really great and we already know this right because when people take anti therapy you’re not just taking one drug right you’re actually taking three uh or more drugs which are they’re being used in uh in synchrony to to be be able to to to to reach undetectable levels of Aria are you using Spinone and SP and DCA yes and art all together or just the two so right now we’re we’re using them uh uh together without art okay but I I I the way I would Envision these drugs from being used in a clinic would be in combination with art uh I don’t think that either one of these drugs can be used without art at least initially okay so they they wouldn’t be Frontline therapy drugs they would be drugs that would be given in combination with art again with the caveat that if you let for instance no matter how long you take uh art if you ever stop taking it then the the virus rebounds right so uh but with these drugs we have the potential that after a while of taking them you might be able to stop taking them and then not have any viral reactivations that’s the difference between transcription Inhibitors and the art that’s currently available art that we currently take of course does not offer a functional cure unfortunately whereas these drugs uh have the potential of doing so okay so does art that falls under like the block you’re blocking the HIV replication and then the lock would be the spiral actone and the DCA coming in locking it in place yes yes well I think you can you can also look at uh SP and DCA as being both block and lock because they are doing a good job uh just like art uh of of preventing virus from being produced okay they’re just not as good as art uh uh by themselves at doing that so you kind of need art to to help them get the job of getting you down to un detectable levels um but but you absolutely right that the art and SP and DCA they’re both going to be working in in in and basically together in order to reach the the block and the lock of the virus but the the main part part is the blocking right that’s that’s what the SP andd say are really really important for which is preventing that virus from ever being able to to wake up effectively and I won’t ask you to to explain the details of of these charts but can you say um generally what your findings are in using spaone DCA why you’re hopeful about the potential yes absolutely so so the main finding that we have is when we take uh cells and these are cells that are infected with a uh with HIV um um that if you if you keep these cells in in cell culture meaning you keep them alive in a test Loop for very long and you you you keep them in the presence of both DCA and SP so both drugs we’ve been talking about um you actually reach undetectable levels of uh of a virus okay that that’s exciting so so here we’re not talking about R anymore we’re just talking about these two drugs being used in combination okay uh so that’s exciting that we we can reach on the table s uh but what’s even more important is that uh you can actually remove uh after 324 days so almost after a whole year of these cells being in the presence of the drugs you can actually remove these drugs from the cells so now the cells are just you know in theory the cells should rebound right like that’s that’s what you would expect you expect if a cells infected with HIV and you remove the treatment that the that that the viral levels will go back up but that’s not what happened okay so the the combination of SP and DCA have been able to maintain the virus at undetectable levels and not just that but this is the the real powerful thing that it’s it’s really exciting and it’s it’s really novel is that you can then take those cells uh that have been without any drug treatment for 90 days and you can give HIV candy to those cells okay so it’s basically a candy for the HIV and say go ahead HIV I want you to wake up right wake up uh and even though you give HIV candy which uh these are called the uh latency reversal agents you cannot wake up the the virus so the virus is effectively dormant uh and it’s so so much asleep that you cannot wake it up no matter how hard you try again these just only a cell culture but it is a very very important experiment to show that you can actually block cells into a deep latency with basically a deep sleep that you can’t wake them up from so I’m sure the folks at home are wondering when when can I get a hold of that like what what’s next as far as like clinical trials or where do you go from here yeah so I think the the the first step to to do this uh is to go into a mouse we know SP is safe but we want to make sure we go through the safety uh uh uh of using both of these draws in combination in an actual animal uh and then once we we make sure that this is working a mouse then you might go into a non-human primate so use a monkey and then after the monkey that’s when you would actually go into people that’s kind of like the pathway uh progression so we’re at it’s exciting we’re at the early stages of this uh but again hope has it’s a huge collaboratory you have a lot of of different Laboratories involved in this so we have Specialists and people that deal with miles we have Specialists and people that deal with these non-human primates so we have a whole team of scientists who can who are we’re going to be working really hard to bring this to the clinic as quickly as possible right and the the last common I’ll say about this is that uh the reason why these transcription Inhibitors are also really powerful uh with you know if that wasn’t cool enough uh is that people who are living with HIV uh who are taking art uh regularly they will have undetectable levels of virus that we know right and because they’re not detectable they can’t transmit it which is great the problem is that uh we’re now becoming more and more aware that even though uh they have undetectable levels of virus they still have chronic inflammation so you still have residual expression so you have a little bit of of of of V of antigens we call antigens of foreign proteins be made which causes this chronic inflammation chronic immune activation and I appreciate you bringing that up because that’s something that we’re starting to discuss in the channel and dive into yes so that’s on top of mind for a lot of people yes absolutely so we’re very aware of that uh we’re looking to ways of of approaching that and we think that transcription Inhibitors are a really big way in which you can prevent that immuno activation from happening right because if there’s no if there’s no Copy being made uh there’s not going to be any protein being made and the immuno immune activation is coming from the protein so if you stop the copy you’re never going to get that Activation so people going to be able to live longer and live healthier uh because you’re not going to have that the the immune activation that we currently do so even before potentially reaching the step for cure it could potentially be used just to stop chronic inflammation and all the comorbidities that go along with that absolutely absolutely so it’s uh we we’re a rush to get this to the clinic and to get into people because yes even without a functional cure this is already a a big deal in terms of help improving people’s quality of life okay thank you so much for that explanation aw I didn’t know half of that so that’s great awesome my pleasure and by the way guys if you enjoy Ruben’s talk um I’m considering and highly likely that I’ll bring him on in the future to kind of break down what HIV virus is the different parts and and just make it easy for you all to understand so that we can go beyond HIV 101 and kind of begin to learn together more and more about science and research awesome thank you appreciate you guys see you soon all right guys so now I’m here with Clinton to explain his poster I’ll let you kick it off okay so um oh and you’re with you’re with hope yes I’m with hope I’m with yeah okay great so in my lab we are trying to identify new proteins that are involved in the activation of transcription of HIV or in the latency uh state of HIV uh so to do that we use a technique called chapm basically uh we’re trying to identify all the proteins involved in the uh promoter of HIV so like the parts that start the the transcription of HIV okay the chap Ms is a process to find those proteins yes exactly so it’s a combination of of different technique chip chromatin imuno precipitation uh crisper cast 9 okay and mass spectrometry I’m sure people have heard of crisper crisper yeah yeah and the last one was mass spectrometry so Mass spectrometry Ms this is a analytical technique that will identify the protein uh based on the mass of the pro the protein and specifically here on the uh HIV promoter either on the active state of HIV or in the latent state of HIV we found proteins that we already know have been involved in these two states but also novel factors that we had no idea they were here uh one of them is fp3 fp3 is which one fp3 here fubp3 yeah okay so the file Upstream binding protein three um It’s A protein that is known to bind single stranded DNA to uh control gene expression so we were thinking maybe is also controlling gene expression of HIV um so we’re trying to investigate exactly meaning maybe either activating it or inactivating it exactly and in this particular case in in the activation of HIV because it was find in the active state of HIV gotcha okay um so first of all we confirm that it was in indeed part of the activation of HIV we knock down so we remove of the cells and we see a decrease of the activation so we were pretty happy of that and then next step we reintroduced e the cells and we have the risk Q so we have an increase of HIV activation okay so so you saw a direct correlation correlation took it out or when you introduced it and that’s a protein it’s a protein yeah okay and also we found that it was required for infection because when we remove that protein uh before infecting cells uh we found that we have a depletion of HIV activation transcription and expression we have less uh uh RNA uh of HIV and we have less proteins uh um of HIV in the case p24 so that was quite interesting uh then now that we have confirmed kind of the role of fp3 there we wanted to investigate exactly how this work how3 somehow control this activation of hi of HIV so we uh we run an experiment called chip chromatin imuno precipitation and we found that a frry is interacting can you say the name of the experiment again chip chatin imuno precipitation okay and we found that fp3 was interacting specifically at two location of the HIV genome and that is a clear evidence of the genome is the DNA of the DNA of HIV HIV on the gene of HIV so that’s protein is interacting on two points on that DNA yes okay two close points two close points yes okay is that significant that they’re close yes it is significant uh because it’s on the HIV promoter so where the the the transcription start where the expression of H starts MH and and it is a clear confirmation of first the the screening that we have done where we have this enrichment specifically in this location and also we have this evidence of direct or indirect binding of the protein uh in that part of the HIV Gene so now we what we’re trying to to find is uh why F3 is there what is it doing does it help the the recruitment of all factors does it help the other proteins to to elongate the HIV transcription we don’t know yet that’s what we are trying to fun and that’s basically where we at well I have to say it’s fascinating um for people outside of science the things that you’re able to accomplish and figure out like these are things that are on microscopic level that we can’t see with our own eyes and somehow you’re able to to do all these things it’s uh it’s really incredible thank you and so that’s the next step do you have a a plan or yes we have a plan so we are trying so now we have like a local view of what’s Happening we’re trying to find uh on the genome wide view what fp3 is is interacting with uh so it does it interact with other genes does it interact with other proteins yeah to like find the the the final Story the final mechanism by which if activate once you understand how it works then you might be able to manipulate that exactly um we can somehow uh uh in in inhibit the proteins and uh uh uh inhibit the HIV transcription and activation or could you also use it to activate latent we can we could also do the res we could also do the contrary and uh uh yes that’s other that’s what other labs are trying to do to reactivate uh uh uh latency so that they can be able to kill the cells that have this uh HIV Gene Y and are you able to expl explain how you’re able to figure out how it’s interacting with other proteins oh uh yes so how we can do that is uh by uh coip so imuno precipitation we have fbp3 we try to pull down the protein and we try to find what is binding to in terms of other pro pro of other proteins and that we can is culture uh no so that’s you have the liet or okay that’s going to be that’s going to be yes too complicated but are you introducing um single proteins at a time to see if there’s an interaction uh no that’s going to be a mixture of the all the proteins that we can find in cells we we uh add fp3 we pull down and we try to find what other proteins have been pulled down at the same time oh okay that’s basically the interesting okay fascinating that’s great great job and I appreciate you taking the time to explain no problem did well thank you all all right folks now I’m here with Aiden to talk about her poster so I’ll let her take over okay um so primarily are you familiar with bastat no so it’s an hdac inhibitor that actually failed clinical trials because it wasn’t able to do enough in terms of HIV latency reversal um okay can you explain what an hdac inhibitor is okay so hdac Inhibitors um it’s the histone de atilas Inhibitors so they allow the chromatin to be within your DNA to be able to loosen um so that transcription factors are allowed to get in and transcribe DNA better okay um but yeah so it failed clinical trials because it wasn’t able to do enough in terms of HIV latency reversal so our I guess question was how can we what can we do to enhance this process so that it can go through clinical trials in terms of H treatment so okay let me get this clear the hdac inhibitor would actually encourage transcription yes it encourages the transcription so that we can we can awaken the cells um out of their dormant State and to remind folks uh who are watching HIV transcription is replication of the of the viral DNA so that it can spread do its spiral RNA to other cells and that’s how it infects and so the htac inhibitor they they actually want want it to start doing what the transcription yes because we can’t find or attack latent reservoirs while they’re they’re silent yes they’re hiding in your body so by using the H Inhibitors it wakes up those so that we can find them and then get rid of them very good okay okay so it failed clinical trials initially it failed clinical trials it wasn’t able to do enough for lat and rival it didn’t make it through clinical trials gotcha um so we’re trying to figure out what we can add to it just to clarify clinical trials means working with humans at that point yes clinicals are working with humans gotcha okay um so that’s so that’s kind of like late stage to go to get to the point where you’re actually working with humans as opposed to mice or non-human primates that’s kind of a big deal we know it’s it’s safe yeah and a lot of work went into getting it there and then to fail clinical trials is so and so and and that’s a really good point because there are as you can see you’re just seeing a small portion of of the researchers that are working on all this stuff and they all have their own experiments to have their own clinical trials and it’s it’s I’m sure it’s like really uh disappointing when things don’t count out the way that you hope unfortunately 99% of research is failure but it’s learning from those failures that’s the most important part of trying to move forward and how do you do you do you get trained at all on how to build that resiliency in yourself like professionally to like be able to withstand the constant failure failure failure and know that that’s just part of the process honestly since I I am so new to the research world I just finished my my bachelor’s degree in May and so I congratulations I’ve been thrown into it and it’s definitely I feel like it’s going to be tough at first getting used to the amount of failure that is going to be experienced get emotionally involved yes I mean it’s your work that’s your baby that you’ve spent so much months and so much work preparing for and then but it’s part of the process and you know just being able to you know if something fails it’s what’s the next step how can we work past it what can we do to get it to move forward exactly Etc Great okay so we use we tried to repurpose a treatment that actually was FDA approved for ovarian tumors um and they for treating ovarian tumors they used hdac Inhibitors in combination with parp Inhibitors um which are the poly ADP ribos polymerase okay super family of enzymes and that was able to successfully treat ovarian tumor so we wanted to be able to repurpose that and try to put that into increasing our um efficacy for does that also work with the transcription it also encourages that in yes um the specific enzyme there’s 14 enzymes within the par family and we focused on tank eras um for our project and we hypothesized that it was these two different Pathways that would be able to work for our kick and kill method that we are trying to utilize are you familiar with kick and kill method is that um is that similar to shock and kill yes it’s it’s basically the renamed version of shock and kill it is okay same thing but K kill sounds better cuz we talked about shock and kill in my weekly H News videos so some of you who will follow my content will be familiar with shock and kill do you want me to say shock and kill instead would that be easier kick and kill it’s the new it’s the new term kick and kill 2.0 yeah um so the combination of the H Inhibitors and the parp Inhibitors worked on treating ovarian tumors we wanted to see if we could utilize both of those to treat HIV tumors or HIV cells as well and we did this why we tested three different kinds of cell lines cell lines aren’t human primary cells um which is kind of our next step is to try to recreate all this research in human primary cells but we use jot cell lines um and we treated them with the HD Inhibitors as well as the par Inhibitors and then measured them with a flow cytometer to see if they had flues so our jot cells when they are latent um don’t express any of the green fosin proteins it’s less than 1% um that they do Express and so after treated with our HD Inhibitors and our carp Inhibitors if successful they would have reactivated and would fluores so when you look under a microscope you actually see fluorescent light close cytometer oh okay gotta so we use the flow cytometer to measure the fluoresence gotcha and this the fluoresence means that it’s activated yes it means that we’ve successfully activated those latent cells by the we measur that by the expression yes that’s a good thing in this case um and so we actually found the par Inhibitors alone weren’t able to do anything in terms of latency reversal but in combination with our HD Inhibitors we saw three to fourfold increase in latency reversal efficacy um which is very successful so yeah I mean that’s that’s basically uh to create this into human primary cells since we just used the cell lines right um it’s you know it’s good to get a basic sense of working with cell lines but it’s the important part is to be able to recreate that in human primary cells and then you kind of take the next steps you can do mice you can do non-human primates Etc um progression to human clinical trials so this is just this is the base of all of those steps of research yes and also we mainly focused on the latency reverse aspect of the kick and kill method and so our next steps would also include focusing more on the kill method and how can we get those immune cells stimulated more to be able to you know kill those cells that we’ve now you know brought out of their Laing form excellent amazing thank you so much this is the new face of Futures HIV science I hope we’ll get there someday maybe awesome well you did a great job thank Youk you all right everyone so now I’m with Andrew to talk about his poster away so hey everyone so my poster uh mainly focuses on the use of spironolactone uh and its effect that it can have in a non-human primate model um with it or with HIV infection as well so originally we decided to look at spironolactone because um it was found that it specifically degrades xpb which is a subunit of a complex that’s very important for initiation of HIV transcription okay so so SPV can you um break that down what SPV what’s SPV so so it’s SP is short for spon Al lactone but then you said something else SPV is a something xpb xpb okay what’s xpb so xpb it’s a subunit of a complex that’s important for initiation so it’s like uh think of it like a bunch of proteins that work together okay so and then basically their job is to start transcribing DNA so it can yeah basically so complexes are are groupings of proteins yes and they serve different functions within a cell yes and this particular complex xpb initiates HIV or yeah HIV transcription yes which is like we’ve been repeating multiple times is uh how HIV replicates itself it’s like the Machinery yes that’s great great um and we’ve heard about spiral actone with uh Rubin as well so that’s great we’re starting to hear the same uh terms more than once um okay I’ll let you take it away all right great so yeah that’s kind of the background of what SP is and so basically originally we were using it in a cell model to look at how it can affect HIV transcription and we saw that when SP was used in combination with antiretrovial therapy we could drop HIV almost below the limit of detection compared to Art alone so and this was very promising for us and then then going off of that we also looked a little bit deeper and saw that spirolactone specifically affects uh viral transcripts so HIV transcripts uh in compared to Cellular transcripts which basically means that the drug is specific for targeting HIV transcription gotcha okay following along great so then so that was the cell line model so then we decided to move this was all working with non-human primates so this side was cell line so this was this okay so this is separated okay this is all cell line in a culture yeah in a culture got it so then um basically we went from that and then it turned over into what I did for this project which was going into the non-human primate model and basically this we set up a schedule where we wanted to test whether or not spirolactone could have the same effect in the non-human primate model as it did in the cell culture model great so we set up a model where every two weeks uh the monkeys would have an escalating dose of P mhm uh up to 48 milligram per kilogram which is a very high dose so we were expecting that at that high dose we would see um degradation of xpb almost to zero so that was the goal for this was to see how far we could degrade xpb and the more you degrade xpb the less HIV replication is happening or transcription yeah and that’s that’s what we’re hoping to see that’s the goal okay great so if you look here so in the results we see that by the 24 milligram per kilogram uh dose the levels of xpb were reduced by greater than 50% so you can see comparing the black to the red okay so which is very promising that’s what we wanted to see oh I see so that’s what we’re looking at yeah inial and then with and then that SP and then we did that for four animals so yep and then if you want to look at it in the graph form so this is all different concentrations all the way to 48 milligram per kilogram and you can see at the 48 milligram per kilogram time point it was Bally completely gone okay so you’re really seeing the progression as more SP is introduced the xpb expression is that what’s or no the protein level yeah protein level is so it’ll be decreasing dramatically okay yeah and that’s basically what we wanted to see uh this initial non-human primate model was used as kind of a pilot study to make sure that the spir spironolactone did have this effects in the non-human primates and so now the next step would be to use this in an infection model so we can it’s an infection model so basically an infection model is we take the same model that we did with the non-human primate models and it just also happens to be infected with either SIV or shv so semi immuno deficiency virus or Simeon human imuno deficency virus wait what’s the wait because I’ve heard both of those terms so what’s the difference between SIV and HIV so SIV is a specific virus to non-human prates so HIV is a hybrid hybridized virus so it actually is that done in the lab or is that naturally occurring not naturally occurring so yeah it’s a labade virus and it actually um it gives a better idea of how the interaction between say like SP for example would occur in a human Okay so maybe if you’re still worrying worrying about safety then that’s an opportunity where you can you made you’ve made this hybrid so you can potentially see in a non-human Prime how it might affect yeah a human in a human without actually putting it in a human right away yes okay yeah so it gives us a better gen Le so yeah so that’s the status of the work that I’ve done so far um it was also important to note that um we wanted to see to make sure the monkeys could tolerate the drug well yeah and so they how did that turn they did they they were all very happy no negative side effects and the all the blood biochemistry that we did so you know standard you know potassium sodium cbcs all that type of stuff all fell within reference ranges so they were very happy so and so you said the next step is to use shiv yeah either shiv or Si yeah decision that we’re making so and then we can see if okay so these non-human primates didn’t have either otherwise healthy not infected that’s correct okay gotcha yep very cool thank you for explaining that you made it seem so easy even though I’m sure this is way more complicated then it sounds yeah no problem thank you for that I appreciate it yeah of course I’m with Bill right now and he’s going to explain one of these post to us today hi good afternoon um our poster is about a series of partner protections that together community members along with principal investigators and clinicians have put together to ensure the safe and successful um duration of a of a of a clinical study that involves an ATI or analytical treatment Interruption which means that people who are HIV posit have to stop taking their meds or their their life-saving HIV medication in order to have the to figure out if the actual um experimental drug is going to be successful and giving up um taking your sorry to interrupt you but for those of you who want more information on ati’s clinical studies um I actually did an interview with Tom Villa recently it’s it’s live on my YouTube I’ll put a card up here so you can watch that if you want a little background little refresher on what Bill’s going to cover okay okay go ahead okay so um I was just going to say that you know um for me I’ve been positive for over 30 years and I kind of grew up in the a you know when it became you equals you and we no longer had it disclosed you weren’t um worried because you know I was I was on my meds I was undectable I couldn’t transmit on these studies you’re going off your meds and you are able to potentially transmit and that’s a huge thing for your sexual partners and I think that you know we’re already asking a lot of people to go on a study it’s very time consuming um it affects you it affects your life Partners it affects your family um especially for those of us in a Sero polarized relationship where one person is negative and one person is living with HIV yeah yeah my husband is is is not positive okay and he was actually um very concerned with me going on the study um I thought it was important because I’m only here as a result of the people who did the crixivan studies back in in the early 90s it you know I went from act to crix ofan and that was a huge thing so yeah um we think that it’s a you know we have set up some some basic partner protections that we would like to see as part of all clinical studies that that involve an ATI and you know it involves things like the proper site selection you know a robust Community relationship you know the ability to make referrals I mean you know it’s one thing to say get on on prep or have your sex partners get on prep it’s another thing to be able to say here’s how you get on prep here’s where you go so I think that that um that’s kind of what we’re trying to do we’re putting together a toolkit that would be available to people um to the you know part like part of the informed consent that you actually work through and and there’s checklists I mean people don’t know how to disclose anymore you’ve got to disclose not only you’ve got to disclose that you’re HIV positive you’ve got to disclose that you’re now potentially viic you’ve got to disclose that you’re on a study some people don’t understand you have to explain all of those things so that’s why we have put this together I think it’s very important you know we’ve got to you know it will ensure the scientific and social value of an ATI you know it reduces the likelihood of unintended transmission and should there be transmission ensure impr prompt management of any acquired HIV uh infection and so you brought this here specifically so that the science Community can see this yes as well as Community man community members but it’s also you know we have been trying to reach out to the scientific Community because it’s got to be adopted by everyone the community wants this we talk about it at a community level how important that this is we have got to get the investigators you know it’s got to be built into the design of studies that that um you’re again I I can’t get over how much we’re asking people to to to to give up and to um to risk by going on these studies we’ve got to make it really easy and beneficial and I think having having partner protections as a part of the the the entire package would be very helpful excellent thank you so much for the explainer a huge thank you to these wonderfully generous and patient investigators and Community Advocate Elina Pang Ruben tavora Quentin jaabo Aiden mcra Andrew mccauly and Bill freshwater thank you all so much for allowing me to command Deere your poster session without any warning um if you did not understand everything that was discussed by our investigators I hope you learned something and are starting to pick up on maybe a word here or a word there that you didn’t know before like maybe HIV transcription maybe now you know HIV transcription is or if you’ve never heard of spirolactone and the way that it’s used in HIV care research now maybe you know things like that um the goal is definitely not that you walk away from this understanding everything that’s going on but that you just start to like challenge yourself a little bit and be able to engage more with the science in HIV research if you’d like to see more poster session videos like this one hopefully next time with better video and audio let me know in the comments below until next time cheers here it goes here it goes oh here it goes oh here it goes …