he has been head of nihaid since 1984. which is quite an accomplishment. he has been a stalwart champion among vaccine research among many other responsibilities he has leading our nation's hiv research agenda. so, dr. fauci, thank you very much for coming here. we also have joining us mitchell warren who units. avac. used to be the aids vaccine advocacy coalition. we're now avav i'm on the board. we have a big conflict of interest. mitchell talks about the where the research is from a leading advocacy organization focused on hiv prevention. a margie mcglynn is here that runs the international aids vaccine initiative. iavi. runs one of the partnerships bringing together a multiple set of actors to accelerate the development of an hiv vaccine to

hear from here where iavi is and where her partners and prospective from leading pdp in this area. format we'll have 30 minutes for dr. fauci to give us sort after presentation, plenary talk and we'll move to mitchell warren of avac of eight other ten minutes of comments. margie mcglynn as well eight or ten minutes of comments. then we'll open up the pan fell for you to give questions and i will moderate that. a good chance for to you engage with them on discussions where we are with hiv vaccine research and where it is coming. so, dr. faw economy, over -- fauci, over to you, and thank you for coming. [applause] >> so i can advance my own slides? there you go. thank you very much, todd, a real pleasure to be with you here today. i'm going to talk a bit about the issue of the role of an hiv

vaccine. i want to start off by putting into perspective the concept why we really do need an hiv vaccine despite the spectacular successes and really historic successes we'll had over the last several years in arenas in both treatment and prevention. we'll look at the background and i will get into the nitty-gritty where we are with the vaccine. we're aware of the most recent numbers from u.n. aides that keep hiv aids historically among the short list, less than a handful of devastating pandemics that our civilization had to face with the stunning numbers showing now over 75 million total cases, 39 million deaths, 35 million people still living with hiv and as of the last count, 1 1/2 million deaths last year and 2.1 million new

infections. in the united states we're a developed nation. we have drugs, we have health care that is getting better i would say but it is still something that is really very difficult to accept that we have 1.1 million people living with hiv and importantly, about 16 to 18% of them don't know that they're infected. we have had over 600,000 deaths and the number that keeps bothering me for decades is that there are approximately 50,000 new infections every year for decades. that is the amount, the most unacceptable statistic, after all of our prevention modalities, and it's a great example of the disparity in our society because 12% of our society is african-american and 50% of the new infections are among african-americanss, mostly gay african-american men. again it's a disease of youth

but i don't want to get into that right now because i want to move on why do we say we're doing so well? it is really based on decades of extraordinary accomplishments in science. i could spend a half hour on each of these here but the ones that really come to mind are the extraordinary advances in treatment which started off, if you think of the history todd was mentioning that he was involved from the very beginning. i became involved in hiv a week 1/2 after the mmwr came out on june fifth and i've been doing it ever since. but it was a time we didn't know anything, not even what the virus was to now over the years developing treatments where we now have more than 30 fda-approved drugs which have completely transformed the lives of hiv-infected individuals where right now we can say without exaggeration a lost things in medicine when people talk about results exaggerate,

is that if you can put someone on anti-retro virals relatively early in the course of the infection, if they stay on the drug, a 25-year-old hiv-infected man or woman and you can look them in the eye as i do when i see them in my clinic three times a week, tell them if they say on the drug you can project they will live additional, 50, five, zero, years, which is really one of the extraordinary accomplishments in biomedical research and translation. now we have the implementation in middle, low income countries. you're familiar with the pepfar program, global fund, philanthropies, host countries to the point when i first went, not the first time, when i was sent to africa by president bush to try to scope out the pepfar program there were less than 50,000 people receiving therapy. right now we have 13 million people which leads to 7.6 million deaths that are averted globally since 1995.

you superimpose that upon prevention and we have a whole bunch of combination and prevending. -- prevention. some were easy before we knew about it was hiv, condom use, needle exchange, syringe exchange, behavior modification. now we have medical related interventions like sir couple sis shun, mother to child transmission, microbesides, and proif i have lax sis and very important treatment with prevention not only saves the life of the infected person but can prevent them in very high percentage, more than 95%, from transmitting that to another individual. that allow us to talk starting a couple years ago at international aids conference in washington d.c. and hillary clinton came to the nih a few months before and used for the first time a aids-free generation. we can talk about a world

without aids. when you say that given everything we have, one can ask yourself why do we actually really need a vaccine and i'm going to tell you why. so let's take a look at the current status. whether it is essential and what the pathway is. so the current status, the projection in the absence of an hiv vaccine, you can do mathematical models and i always worry about mathematical models. i'm in the middle of an ebola mathematical model that is not helping out very much but that's another story i'm sure steve will think of another session to discuss that. but the projection is that if you look now, we have about 35% decrease since 2005 in deaths. and then when you look at the new infections it is about 38% decrease since 2001. so the current projections is good and if you get to that

mathematical model it depend how much you implement what we already have. so, let's say we don't have a vaccine. we take all the things that put on the prevention slide and everything that i have told you about treatment, the red to blue to green, really means how you increase the implementation of these modalities. if you really put a full-court press on, if pepfar gets funded the way it should get funded, the global fund does what the global fund is supposed to do you could actually see that implementation. you can actually say is an hiv vaccine essential to end the hiv aids pandemic? i wrote an article about this in february of this year, of 2014 and i'm going to talk a little bit about some of the things that i mentioned in that "new england journal of medicine" article. the reason i believe it's necessary is that if you look at some of the challenges that we face about ending the hiv/aids pandemic in the absence of a

vaccine you have to look at the reality, that despite all of the great results there is a thing called care continuum. i don't want to spend time because i've spoken to similar audiences about. that we don't do very well, when you look at access into the system, retention in the system, and adherence to therapy. and you look as a country, we're doing really, really badly about the number of people who are hiv infected and percent of those who are in the health care system stay in a system get on therapy, stay on therapy and drop the viral load to the point they don't infect anybody else. we have a long way to go even though we're doing very well. then there is the social and cultural barriers. i again could spend a lot of time on that, but i won't. such as the lag in implementation of interventions. one example, circumcision. circumcision, now, if you look at the numbers, started off

about 55 to 60% effective and in long term follow-up is about 73% effective. i can not imagine if i had a vaccine that was 73% effective we would be celebrating it on the front page of "the new york times" and yet we don't implement it very well. there is also stigma. we all know about that. there is legal impediments. homosexuality being illegal in a large number of countries which is just mind-boggling when you think about that. so there is a lot of things that are impeding our ability to get to ending the hiv/aids. the other thing is one i think apparent to everybody and that is the whole idea of human nature and recidivism. i've shown this before but i will show it again because it's a great example. when you're interested in other infectious diseases that seem to kind of go away and then they don't go away. malaria is one of them.

this is example of the measurement of malaria parasite prevalence in sans sy bar from 191957 to 1983. there was a program where there was indoor individual spraying reduces parasite prevalence from 76% to less than 5%. so the officials involved in their great wisdom decided they were done with malaria in zanzibar. so they stopped. look what happened to the curve. it went right back. one of the things i'm concerned about is that mathematical model that we always talk about, i'm afraid even in the best of circumstances, if you just take that green line that goes down, and i say 2,000 question mark because i have no idea how long it will take to get there, i'm afraid, given human nature we may start to see that. when we start seeing that there is such a low level of infection and numbers look good, that

we're going to have pa rebound. so my conclusion then is that it really is essential too duringably control and end the duringably control to end the aids epidemic and the. if you really want to nail it, then i think you need to get a vaccine. so let's talk a little bit about the pathway to an effective vaccine. i break it up into three parts, the years of disappointments and unexpected success and the way forward. so the years of disappointment i can real to because cliff lane in my group actually did the first vaccine trial in 1987 with a gp-160 subunit candidate. it was the era of understandable naivete as i like to generously characterize ourselves then. thinking that when every other vaccine, if you vaccinate somebody with an envelope protein they will develop

neutralizing antibodies you will have protection. hiv was a little smarter than that and as it turned out we went years and years. the history of it is truly one of frustrations. first we started off with the b-cell approach. the natural take vaccinologists do. we were wrong because the wrong. body doesn't like to make neutralizing antibodies to hiv. less than 20ers or so make it and do it after one or to years of infection when it is too late. very unique microbe. very unique virus. no other virus act this is way, none, even the worse of the ones you think b ebola is easy. i'm telling you, it is a terrible disease and you make a good immune response. immune response clears the virus and you're good to go forever. would that were the case for hiv. we went through a whole bunch of

trials. we did empirical trials. we did trials with vectors, with proteins. 2003 we said let's just do a phase 3 trial. it failed, both of them. there was no protection. then the field got sort of a lapse in confidence and said we can't prevent infection. let's try to at least suppress viral replication. they switched to a t-cell vaccine which nobody imagines will prevent intech shun but might suppress viral load. that didn't work either. one of the studies showed it actually made individuals more susceptible to infection. once they were vaccinated. which i use as an example why we shouldn't be distributing ebola vaccine before we prove it actually works because we might wind up making people worse but then again that's another story. okay, so what was the unexpected

success? you got to get lucky sometime. so what we did was an i am peeric trial of a pox virus vector with an insert of a bunch of viral components followed by a protein boost. that is what we now refer to as a rv-144, or the now fame must thailand trial which showed a showed a 31% efficacy. that is not ready for prime time but it was a very important study. it was important because it at least proved the concept as marginal as it is, you can actually prevent infection with a vaccine. so it was an enormous prove of concept. so what are we going to do with that? it is very interesting. because for those not involved in following this. i don't expect anybody to follow it that closely but, it was an interesting, fundamental philosophy how you approach a vaccine.

so, that is when i get to the last thing, the way forward. so think about what we're doing over the next several years as two major buckets. one is the rv-144 approach and the other one is what's called structure-based vaccine design or trying to develop a broadly neutralizing antibody because we found something very interesting with the rv-144. the rv-144 approach, this is a blowup, if you look at the bottom of the slide that is the viroon. that is the hiv envelope trimer. that is the key antigen that you want to use. we want to know if you want to get neutralizing antibodies you need to present the trimer so you can see it. we weren't that sophisticated years ago. we took a monimer.

trimmer means three components and you pull that out and we empirically injected it into people having no idea at all what the immune response would be again. let's see what happens. we injected it into people. that is blowing it up. we found out among those 31% who were infected, they had an immune response against a particular epitope was in the v-1, v-2 region of envelope. v-1, v-2, means it is one of the variable region on of the envelope. it changeses from strain to strain and mutation to mutation. we identified an antibody. we then, only by extrapolating backwards did we say that that's the site that you really want to make an antibody against. so we threw it in and said okay, that is the immune correlate. now what do you do?

you have something 31% effective. you say let's amplify it. you amplify it by increasing the strength of the response, namely how much antibody you make. you increase the breadth of the response, can it be broadly against multiple strains. and you increase the durability. does it last for a year or two or maybe three or four? the response in the rvis 44, kept on going down as you -- rv144, kept on going down as you went further with the vaccination. you do that by sticking with the product, doing multiple boost, modifying the vectors and adding a d.j. avents you're not changing any concept. you want to do better in the same concepts that you did before. in fact we're doing it in africa. is there anything different between the thys and africans.

thai. is. if the south african study if you vaccinate them with similar regimen, they make similar response as the thys thais do. we're planning a large study using same concept as rv144 in africa, that if it works in high-risk, head sexual population as oppose toed. population we had in thailand. note the title of the slide is alternative strategies and parallel tracks and that is structure-based vaccine design, namely trying to develop newt alizeing antibodies. let me repeat what i said before. first time we took an envelope. we had no idea the immune response we were looking for but we injected them. we found out what the immune response was and said, ah, let's amplify that immune response. when you look at structure-based

vaccine design it is exactly the opposite. and let me explain. so this is the trimer. so you go to a whole bunch of hi investment infected individuals and you are they making broadly neutralizing antibodies. if so, to what are they making it against as opposed to throwing it in and finding out. so if you take these individuals, these 20% of individuals who make broadly neutralizing antibodies and cloned their b cells and do a whole bunch of sophisticated immunology you can identify five parts of the trimer that are actually the targets of neutralizing antibody. so now we know what we want to induce. so you are taking that, you look where the antibodies bind. those are the antibodies, those little squiggly things and they have funny names and numbers we

immune noll gifts kind of like to confuse people with giving them strange things like pg9 and vrco1, things like that. now the antibodies recognize the epitopes. now the challenge is to take those epitopes on the trimer and present it to the body in a way that makes the antibodies we know are neutralizing. so it is going, in other words saying here is what i want to make a response to instead of take this and who knows what you will make a response to. that is called structure-based vaccine design, to get a neutralizing antibody. and when you do that you have to understand what's called b cell lineage. in other words, can you coax the b cells to do what it is you want them to do. so why am i even throwing that up before you? because in natural infection

that doesn't happy very readily. for some reason or other, the b sells don't like to make a broadly neutralizing antibody quickly and readily against hiv. how do we snow that? because 20% of the people do it and it takes them two years to do it. so we got to have, maybe fool the immune system. so how do you do that? well, there was a seminal study that was reported by a colleague, fellow named bart haines who actually many, many years ago was a fellow in my laboratory at the nih who is now at duke and he followed someone who was infected and they knew they were infected really early. so what he did is that he followed the evolution of the antibody mutation with the evolution of the virus mutation. if i had a pointer, i could go through that but i look at my,

talking with my hands italian background and i'll tell you. so what happens is that the virus comes in and the body makes an immune response. the virus mutates and the b cell mutates and makes the response. and it mao tights again until it goes and antibody keeps following that mutation to the point where it is such a great antibody that it is now broadly neutralizing. the only trouble it is it is too late for the patient because they already have so much virus and that neutralizing antibody will not do anything. what it told us, if you selectivelily present to the b cell a changing, evolving immunogen, you can actually coax it to make a broadly neutralizing antibody and that's exactly what the philosophy and the stratif i is right now. to mimic, this is natural infection and on the bottom to

get an immunogen and that is the timer that i'm showing. and vaccinate somebody over time, two on three boost, and to get the antibody. that is the two approaches. one capitalize on the rv144, was the revolt of pure impircism and develop a structure-based vaccine design. that is the opposite of imperism that is structure based and planned. that is where we need to go. i have to mention the t-cell vaccine approaches. we know t-cells are important suppressing virus after infection but again this is a little complicated slide but if you start off in the upper left, the cd4 provides to t-cell

because they need it. it makes cito kind and kill sells that have hi investment-infected t sells. we need it. sells responses in connected with the b cell responses. hiv incidents and deaths i can tell you will continue to decrease in the absence of a vaccine. achieving a timely and i want to underline, sustained end to the liv aids pandemic as i refer to the nail in the could have fin of the pandemic. i describe ad clear scientific path way towards an hiv vaccine and if we integrate non-vaccine with vaccine prevention modalities, then, and only then could do i think we can insure the end of the hiv/aids

pandemic. as i said, in the article that we published, the only guaranty of a sustained end and to get where we want to go so that we can then, with we put up the last slide, it would be a meaningful slide. namely that we will have a world without aids. thank you. [applause] >> i think if we give laser pointers on the end of your fingers we'll all be in great shape. mitchell warren runs avac. he plies brings in the community in the discussion. he has b cells, and t-cells and cyto kind so people like me understand. we asked mitchell to talk about how you generate the kind of advocacy to make sure that dr. fauci and his team have ad

adequate resources but not get people too far ahead. we had dr. fauci estimate vaccines in one year, former secretary of health and former president gave us 10 years. we keep running on. so one of the things mitchells that to do is get people just excited enough to keep the money flowing but not so excited they get ahead out of our actual progress. mitchell, tell us how you work that magic. [applause] >> we'll see if it is magic. the magic is being introduced by a board member. the harder part is following dr. fauci and i have to say one thing. at avac a lot of our work we talk about translation organization, translating very complex science to a range of audiences an translating very complex community issues back into the science and i have to say someone working in this field we often see people woman part mentallize. there are researchers and policy researchers and advocates. i'm advocate and trains late tore when i think dr. fauci is

an advocate and translator as much as i in of us. we often forget. that if which learn anything 30 plus years of epidemic when the constituencies come together that would be true for hiv and certainly true for ebola. i will spend a few minutes to try to provide an advocate perspective in all of that. i was thinking what possibly to say after dr. fauci would speak. i went back in time. avaca. done annual report on the field and seven years ago. three different songs. my favorite one i hope is the least likely to be the one that defines our search for a vaccine. that is we're on a road to know whereby the talking heads. i don't think we are. but in fact if you go back to 2007, and as fauci described there was a sense we were investing and working hard and not making progress. someone on a road to nowhere. as perhaps as we had more and more vaccine candidates out there it seemed sometimes if you

didn't know where you were going any road could take you there. there was a sense i think in the field of shooting a lot of different places but not quite clear where we would take it all. and as i reflected back in preparing for today, what i'm struck by is what a remarkably exciting time we're in right now. and, i don't want to sugarcoat it. i don't know when we'll have a vaccine. i could tell you now we'll have it in a decade. i guess it all depend when you start counting. i would urge you not to start counting too soon. i do think we're one of the most exciting moments scientifically and more broadly in terms of where we are with an aids vaccine and how we're going to get there. part of this last week, 1500 people gathered in cape town, south africa, first ever hiv research prevention conference. i will spend a few minutes why there was a excitement there. i was struck when i woke up monday morning or tuesday morning celebrating jona salk's

100th birthday. every day google does a different design. just reminded me then how important vaccines are. the power after vaccine and how normative that is. what would have been his 100th birthday is reminder of how powerful a vaccine and how no disease will be eliminated without one. 1500 or so people gathered in cape town. dr. fauci was unfortunately not there but he did a great present vision via video. i want to point out all presentations give you latest on aids vaccine and research and development as well as conversations about preexposure prophylaxis and they are cataloged into the website there. it was one of the most invigorating meetings this field had in quite some time. it was in a context that did want to frame a bit. as many of you may know over the last several months, we've been engaged globally in a conversation about the so-called

90, 90, 90 targets. they're really important because they aren't just one target. multiple tar embedded here. every aids conference and report has a new theme and new slogan. this one is 90, 90, 90 the idea is importantly, 90% of the all people infected should be diagnosed as aspirational target. 90% of them should be on treatment and 90% of those on treatment should be virally suppressed. as we know, if people are virally suppressed they not only live long lives but don't transmit the virus. is a bold aspirational target for 2020 or for whenever we get there. as you saw just before me, there is a huge challenge getting that many people tested that many people treated and that many people virally suppressed but target is no list important. global community whether u.s.

epidemic or globally we should be striving towards that. i want to highlight i don't think it is enough. as we talk about global end of epidemic, whatever timeline, we put to it. 90, 90, 90. idea of suppression is fundamental but only end the epidemic when we complete the entire cycle. . . basically what you see our a range of different approaches which were described already. the reason i put this up and the

reason i do challenge you to come to terms with it is as advocates, as policymakers, anyone working in the epidemic, to know the issues that are part in terms of what is happening in the field, what results are being generated and what we need to do with those results are important. i want to highlight, back to five years ago, science is an integrated process as a windows and we had this tantalizing result five years ago. advocates who just don't want an aids vaccine, there one question is what happened? five years ago, where is it? it is a huge challenge to do all that needs to be done to boost that well beyond 31%. what this tries to do is let out a different series of pathways, a range of other vaccine candidates. the bottom line is we don't know which of these are going to work. we hope some of them work and probably some in combination with the challenge is how we articulate that and how do we invest in it? if there were a single wrote for

come a single path, a single trial, a definitive act and we could invest in and get to the result and move on that would be able to be easy question but it's not that at all. i want to spend a few minutes talk that money. at the end of the day as exciting as this science is it takes money. this is work we've done for the last decade in partnership with u.n. aids to track investments not only an aids vaccines but across all of biomedical prevention. you'd have to read all the numbers there to know that something doesn't look quite right in 2013. we saw tremendous increase over the late 1990s and early 2000s and then it began to plateau and decline. it won't surprise you to know the orange bar is used for to government assistance. primarily to nih but also with the military hiv research program, and with the u.s. agency for international development that are a major investor.

you can see the u.s. government is a major investor in this endeavor. last year about $829 invested. that's a number that is a fascinating test to people. id these presentations and there are people who say, we invest $821 we don't have a vaccine that? other people say that's all we are investing? that all depends on what else you do in this world. i want to provide one historical analogy. back to the polio experience. you may remember, or may read about the days of fdr and his attorney collecting times in the march of dimes for polio. we take great pleasure in knowing there to polio vaccines, invested in by the march of dimes. but at its height at all of that money was collected, and most about 10% of it was invest in polio vaccine r&d. the other 90% was invest in public education and in care and

support. i would argue as you think but $820 million, is it too much or not enough to put into context of the global aids response but as we spend $17 billion, money that needs to be spent and, in fact, increased to meet the ambitious target for treatment and prevention and delivery. we cannot not invest in aids vaccine. the 820 million would go back up in the 900 range. it would be invested well and wisely. because it really is a long-term investment to come ashore earlier, to finally sustain the end of the epidemic. just to show you the nih at the top, not surprising the bill and linda -- bill and melinda gates hiand all the investment is important that you can see as european funding declined last several years it made little difference in the over all. it's went nih and gates and others, when the big numbers stay big and stay significant in

their investment do have a robust pipeline of ideas and activities that get funded. what do we do now? we heard from the lead scientist in policymaker perspective, i would simply tackle it, that we duty to invest in what is called the p5 strategy, the partnership to build on that high vaccine result in both south and southern africa and thailand. we have to chase that. but we do better than 31%? we don't know but you can't not explore the. we have to look at a range of the other ideas that are on that slide previously a begin highlight there are other ideas. while they were? we don't know. that's why we do the clinical trial. clinical research needs significant investment. all of the work around that structure, around all these exciting neutralizing antibodies that have their clever codenames for what they are, each of those needs to be pursued and the need to be pursued in quite a different way than we worked before. how do you translate that novel

idea into a vaccine candidate, into a clinical trial? when you walk the halls today in cape town last week or any other vaccine meeting you go to, the scientists are beyond excited but how do you capture that into communities with the trials are still in number of years off? we need to invest in all of those. delivering what we have today, while we continue to develop the tools we need for tomorrow. i think that' is a fairly consit theme from what you're before me and after me. but i want to highlight one other piece of information, i think from keeping hope alive so to speak in aids vaccines is so very important. we have to be honest and convey both the credible scientific promise that we have, better promise, that excitement than we've had in decades but we have to honest about the timeline. they will take long and there is no benefit in falsely promising that a vaccine will be licensed anytime soon. we don't actually know.

i always been a believer in under promising and over delivering. i think that's important as we think about these timelines. we have to prepare policymakers, funders for the local. we need to prepare them for both the incredibly challenging trials to come but also to be sure they are there to invest in the fruits of that research when we get it and that we can act on positive results as we're doing. i do want to say as we do all of this work to deliver what we have today and think about the trials for tomorrow, one of the peace i think is so very important is that the clinical trials of tomorrow will undoubtedly be more challenging than they were in the past. as hard as the science has been and it's right getting some of the results have been, the future trials will be undoubtedly more complex because we will be running the next wave of trials in south africa where we're seeking up, providing hopefully oral preexposure

prophylactics, where we will hope we provided micro pigs second two different candidates will have results next in south africa. if they are positive, women will need access. when we are ready to embark on the next large efficacy trial in late 2016 from early 2017, i hope it is at a time when it but this is going down. that means to try will be larger, it may take longer, it may cost a little more money but it is absolutely essential that we do the right thing in designing the house, providing peopleverything we know they can use but still recognizing that the contribution and a vaccine trial is to get as what is clearly the ultimate revenge an option. that is an aids vaccine. thanks very much. [applause] >> the thanks, mitchell. we are not going to hear from margie mcglynn. she spent 26 years i believe at merck.

whenever jobs was to lead their efforts on the step drop, and other vaccine product that mark hazlett. is also rich in and getting merck to reduce its prices for delivering its anti-retroviral component into the developing world, better than the previous one of suing nelson mandela. so it's a really great opportunity to from someone who's been involved in industry and now has taken a moment of her life to help us on an aids vaccine by leading. margie, thank you very much for coming. >> thank you, todd. and to mitchell's point, it's very difficult to forestall such an esteemed scientific leader was also an advocate, and an esteemed advocate who also knows a lot about the science. there are terrific colleagues who work with in this field, and to think the task at hand calls for the best of all disciplines to step forward. and so the organization that i lead, let's see -- i don't have the right slide of your. every go.

your position i lead is called the international aids vaccine initiative and many of you are from a with the product develop a partnership. we are anywhere between our team-15, depending on how you define the term of these types of organizations that were started primarily between the mid '90s through the early 2000 they were started because of market failures, that there were some diseases, especially affecting the poorest countries of the world where there were not enough incentives for commercial organizations to step forward and develop a vaccine or to develop a treatment or a diagnostic test. hiv isn't necessarily a market failure. i believe there will be a commercial market for an hiv vaccine although the road has been difficult and different companies have invested at different times along the road. i can tell you when you get burned by significant investment, and certainly mark was with the step trial, it

really causes companies to stake we take a step back and i want to wait until there's proof of content to think that's good we think about the role of an organization like iavi, how can we help to facilitate the transfer of the science take it as proof of concept? i'll come back and talk will be more about that in a moment to but let me first add more commentary on some of the modeling work, and becaus it gim a little bit bolder than dr. fauci. i put yours down on my craft but a model is only as good as the assumptions that go into it. so there's only one thing we can all say for certain about this model, and that it's wrong, but it's demonstrative. there's a few things i like to point out about this model. this model begins with, let's look at the purple line, that's the unaids enhanced investment framework. some of you may remember in 2011 a publication where unaids put forward a modeling project that

answered the question, if we fully invest in the tools that are available today and we get 100% rollout of these programs everywhere there needed and we get pretty aggressive enrollment, adherents, targets achieved, what can we achieve? unaids will admit this was aspiration. it's the best we could do with what we have been. you will see the model, then it went to 2050 but it's been updated to go out to 2070. we make it down to half a million new infections a year and has extremely optimistic for many of the reasons that dr. fauci went through but that's the best we can do without a vaccine. then you at a vaccine, and again assumptions, i assumed a launch date of 2027 because i always answer the question when will we have a vaccine, i was a i can get pretty good sense ones with proof of concept we should have won on the market continued. so proof of concept means you have a candidate that action has shown the ability to prevent

infection or sing of the control viral load. i don't believe we are there yet. yes, we have a hint of that at the rv-144 travel once we get that i think all of the industry metrics would tell you we can get there in about 18 year period. but since we don't know if we'll ever achieve those optimistic assumptions, we worked with unaids and other partners, funded by usaid, and will look at alternative scenarios. what if the green line happened, that we stayed at the current trend, funded as we are now about 19 billion a year, continue to have problems with acceptance of these programs. if that were to happen, the green dashed line shows should have an even more significant impact of the vaccine. chances are we will be somewhere in between because we can do better than we're doing today, and there's for strong funding support, very strong moral

support throughout the world. so we showed a 50% scale up scenario just to shape what that looks like. on the far right you can see the cumulative number of new inspections that will be averted over this time period for those different scenarios. so whether it's 16 million or 42 million, that's a lot of lives being saved, and a huge burden of illness, huge burden of cost being avoided. clearly all of us should maintain the commitment that we have, the excitement we have what a world without aids could look like. is dr. fauci said, a vaccine making that happen quicker, but there importantly sustainably. one of the modeling slide i'd like to show you looks at other new prevention technologies, and again the purple line shows that enhanced investment framework. we then show the next line down which i think is read. if you were to add on

preexposure prophylactics, and that is you take an uninfected individual who has a relationship with an infected person, and you prophylaxis them with antiretrovirals. you can prevent a significant percentage of infection by doing that. there's been problems with uptake of the reasons that i won't go into today but if you're able to overcome some of the objectives, chechens to a dog can do. i think a of the media last week we are a lot of enthusiasm for approaches able to do that. you could see that additional declined to give you independently took the investment framework and add-on treatment as prevention, and that is treating ra to significantly decrease the likelihood that person to infect a partner come you didn't go down to the green line all of it under 400,000 new infections a year. if you independently took that, enhanced investment framework and add on a vaccine, i showed you that the that's the purple

line. but if you do all of those in combination with the approaches that were available when didn't investment framework was developed and 2011 you can get down to under 50,000 new infections a year and i think you can safely say we will bring about the end of aids and will have an aids-free generation. what does it take to do that? it takes the resolve you've heard so much already. it takes to sustain funding, and just a comment on funding but as i was looking at the chart that mitchell showed i was thinking back to my days at merck. once you start to move through a development cycle from what you start to get some real promising results with you think is where we are right now sorely with broadly neutlizing antibodies, sorting with the rv-144 result, you're spending usually escalates dramatically. it may go up to, threefold. the fact we are down 10, 15% is worsened by the fact that we

really should be increasing exponentially. and so we all have to work hard to make sure that that story is or. women we're ready to move forward with large-scale trials and manufacturing costs that the fun is there to support that. so the organization that i laid as i said was developed because global experts came together and said we really need an organization that is solely dedicated to the development of an aids vaccine that can help work with all the different parties out there and ensure that that happens. we are a not-for-profit organization monday through government, especially the u.s. government and particularly usaid but also in a.i.d., some european governments and the gates foundation is our largest foundation donor and we have other smaller foundation donors as well. so the role that we try to play in what i would call that transitional space. we do not have the research

expertise that you would see in the public sector such as in aid or in academia. but when those discoveries are there, what we have in house are some laboratory capabilities as well as a lot of external partners including biotech companies, contract manufacturers people also a lo of product development expertise. we've conducted over 20 phase one trials partner in africa. one in india of over 12 vaccine candidates. so we have in house individuals, primarily from industry who have joined us better able to advance candidates coming from other researchers, helping to turn those promising discoveries into actual vaccine candidates. we have a clinical trials network liberia in africa, also all of it in india but primary funding for that is usaid will also find similar product developer work as well.

and so through that network we've been able to make a lot of contributions first in the epidemiology of hiv, also is dr. fauci talked about the broadly neutralizing antibodies. we utilize those centers to help us to gather samples of the hiv-positive patients to contribute to the design of the ultimate vaccine products. we have an expansion program of our activities. we are not adding more sites. we have nine clinical trial centers and five have been countries by an expansion program to help build 20 for 23d greater extent the scientific leadership coming from africa to help build that infrastructure that will help for the next major global health threat that emerges, and certainly has a lot of ancillary benefits within africa. so i'll real goal is to get to that red star, to get with the concept. we are not equipped to bring a vaccine to market to some of us are individual but as an organization we are not equipped to do that. we are going to need a major

pharma, make a vexing company and/or emerging-market manufacturer that were taught but delivering the vexing to the developing world, and there are other examples where that has been done without a major company involved. i do believe that pharma companies will be there. some of them are remaking investment in early stages of research. at this point primarily santa fee, j. and j. and a little bit glaxo. i believe that as we get to that proof of concept that we will have motivated partners who will help us with the massive building of manufacturing capacity that will be needed and the massive undertaking of launching a vexing like this. end of 100 countries of the world that will need it. so i'm very optimistic about where we are the yes, it's been a long winding road but there are other vaccines that are taken longer. in fact, i have a chart i often

show that there are several factions that took 40, 50, 60 years to get to market. i'd like to point to the number for polio and that was 40, 50 years perhaps and ask the question, what if we've given up on it polio vaccine? imagine what the world would be like today. and so let's all move together with the resolve that we're not going to give up on an hiv vaccine. we are absolutely committed it's going to happen. it's going to happen within our lifetime but it's going to happen while tony faucher still the director of niaid and then he's not going to retire until he does it. fortune is in great health and distill out jogging every day. but really any support any of you can provide to make sure that that resolve continues will be for a good cause that we can all want to be proud of leaving a generation down the road free of the aids virus. thank you. [applause]

>> and thanks to our donors as well. can't forget that. >> so hopefully the microphones are on. this is a chance for you to of questions and answers with the pandas but i'm just going to kick off with one and then we will open a. we have microphones around the room. take those questions. i would ask when you ask a question if you could give osha and an editor with an organization, tell us which organization before you ask the question. one of the things that came out of the discussion around polio is the stick-to-itness. so certainly it took some ticket the vexing but now we are seeing some dilution of commitments to seeing through the final eradication of polio virus. and over the years you seen spurts, if you will, of energy.

congressman porter and senator barbara is another, a doubling of the nih budget and it's almost as if you pay for the later by seeing the flat-lining of the nhp budget coments were that result in the flat-lining of the hiv budget along with the nih overall budget. so what do we do to sort of keep the energy going and get the escalation back that we need to see and financing terms of political energy? mitchell, why did you start, and dr. fauci, you sort is spent a lot of time with congress. maybe you can help us what the trigger is that we haven't told yet. >> i'm actually more desperate had answered my letter i think part of it is counting -- capping some successes. we do have this challenge when we have the success in 2009 to an enormous amount of work has happened since then. it's hard to describe. it's not easy to breed

policymakers on the core list of risk and why that matters for a vaccine. i think we need to do better at articulating some of those promising things that have been happening at her ticket what we need to do next. the polio side, as hard as the science is i don't think we should ever assume that the delivery part is easy. i would argue as hard as the science is, delivered will be even harder. we need to be prepared for that, for an aids vaccine. at the science brings us excitement and the delivery brings us more challenges. on a vaccine site we are articulating where we are and what are the specific things we should be excepting in the foreseeable future. >> and dr. fauci. >> when you talk about budgets this is a very unusual time. there is no new money for anything. you can make -- i was a get out there and make and you can make all the arguments you want. there's no new money for anything, literally. so the budget has been flat.

it likely under these circumstances will stay flat. that doesn't mean you shouldn't continue to try to advocate for important things. vaccine, hiv come important. you could argue that money in the far and global fund in some respects, i was a more important but as important -- 4. we have a scientific challenge with a vaccine that is still in the discovery phase as opposed to the implantation phase. so what i would say rather, not to avoid your question to is that we always can use more money. i'm always arguing for more money. i get in trouble sometimes but i'm always arguing for more money. it will increase the pace of where we're going, but it's no guarantee. so right now we still a scientific challenges so we really need to do the best that we can with the scientific challenge. and then when we get to the

implantation been effectively put the full-court press on, on the implementation. the difference with polio is that polio vaccine is a really easy vaccine -- i'm sorry. they were good friends of mine by this is easy. you just needed to do it. why is easy? because 90% plus of people get infected with polio do fine. a very small percent, everyone recovers makes an immune response that is protected at all you got to do is induce it. then the obligation as you mentioned is the problem. why have a we eradicated polio after all these years? if very much an implementation issue but we do with hiv as a scientific problem, not an implementation problem. it isn't direct -- we're putting a lot of money in the edges of

people to want to put so much, or how can haven't put enough? i think we need to continue to push hard to make vaccine a very high priority. >> i hear you saying that it is much of science as -- >> it really is. >> the other challenge, all the of the prevention motel with doctor is the after human part of it which is getting people to use them and keep using them. so margie, you have to convince donors to continue to promote iavi. jeff sluman of the table. how do you make this case in the ever-changing world of washington, d.c.? >> absolutely, and you need data. first of all you need to show modeling slides like what we showed here today. especially when a lot of laypeople think that we actually have an hiv vaccine. preexposure prophylaxis and treatment is prevention put it was interesting how it all had to go back and re-educate our

audience. this is what a vaccine is and this is what we've do differently. you need to talk about what will the impact be, how will it affect funding. i didn't have time today to go into that but we are starting the model that if we look at total treatment cost of a for hiv come estimated about $19 billion globally. as you start to see obligations of the vaccine, how does that come down? we showed all a bit of that data in cape town last week. the lines start to cross a little after 2050. so does better contribute hundreds of millions, talk about national governments are contributing hundreds of millions to organizations act the global fund which is great to help treat hiv, well, they have to have a long-term view and realize if they also can invest in millions of dollars, that's we are asking for here, it's like if we had one 20th of what they're giving to the

global front, you can see that total treatment line come down over time. so it's all about data and it's all about telling the story in its own but getting them to realize what the implications would be if we are successful. >> i'm smiling because today is election day, right? you had to work about shareholders that a focus on quarterly profits. that timeline of attention in this is probably shorter than a quarter. the fact is that this is an argument keep making over and over and over and over again. so retention of message is probably a challenge. why don't we open it up for questions. i have lots them ahead by want to get into. why don't we go right to the back of the room. >> thank you. i'm doctor barb morrow -- dr. bob amaro. as i was tested by the introduction of a new kind of vaccine dr. fauci, by your

presentation of the iterative approach. i was wondering what does it look like for the individual that's challenging enough to have a three, four, those is to deliver? do you envision a vaccine where there will be multiple boosts? and how do we prepare to approach that social challenge of behavior change? because people are still rather poorly trained to take the vexing. >> that's a very good question, and i hope it isn't multiple, multiple. so if you look, really at the signs of a you would want to trigger a detail that is one that recognizes and epitope that is out to going to get to the fancy net maturation you want without having to mutate multiple times. i'll try to explain it simply for non-immunologist. the higher the affinity or the

more power the antibody has to bind onto the hiv, the more you evolve and mutate the genes of the cell mutate and mutate and mutate, until they build up a really tight affinity. so we know that the really good antibodies are highly mutational. the reason they are is that hiv, when you get infected, just keeps replicating and bombarding your immune system. at for you, but it ultimately leads to this antibody that's a really good one. now, how do you do that with a vaccine? that's the challenge. you have to be able to give it a form that it doesn't take as you are suggesting seven boosts to get there. because if it does it may be scientifically interesting but it's a nonstarter when it comes to a vaccine. so you try to fashion it in a way that you need maybe one or

two to get there. you've got to capture the cells that only requires a couple of iterations. i would say to would be good. three maybe, but when you get to six and seven, i think it's not practical. so you're right on target with your question. >> we have seen with other vaccines with require re- dosing, penetration rate certainly affects the overall effectiveness. any of the responses? questions. here in the middle. why don't we do a couple? we will do a couple in a row and they can and should. >> doctor ted the daily with johns hopkins. a couple for mitchell warren and margaret as well. dr. fauci pointed out he mapped the scientific method i want to maybe build on that, the analogy to call them and ask about the legal pathway, a policy pathway for curing that.

the issue i have goes back to jonas salk's quote about he would sooner patent his son. incubus on the difficulty we have in the late 90s with intellectual property seems fitting to the doha round and living to -- even though we're in a doha world with hepatitis c can we're seeing significant barriers to access to new drug acting at the prospect am wondering about the terms of these predevelopment partnerships that you talk about. the conditions and terms of those so that we can ensure the price of the vexing such that update actually isn't limited we do in fact realize the promise inherent to these vaccines. >> yes. i'll start on that since it's a very critical issue for us. we consider, funded by governments, platypus, et cetera, and we also consider our mission to ensure that a vaccine is developed for those who need it the most. what you ask is really central

to the work we need to do. we do have intellectual property on any discoveries that we are involved in and but also to get involved in licensing technolo technology. but it's with a clear access provision and we have margin right different able to bring the vexing to the world's poorest countries at affordable prices. we have marched in provisions that we could, in fact, take that license back, find the developing world manufacturer. it's also quite possible that a vaccine make it through the pipeline that has come out of the work of there is researchers involved that has not been licensed by major pharma companies, and especially true if it doesn't necessarily have developed world potential. at merck that was our expectation with the step program because it did not prevent infection to get stimulated immune response to control infection.

so the approach we were taking was how do we find a manufacturing partner that could build a map of capacity that is needed and likely find a partner in the south in a country like india that has the largest vaccine manufactured in the world, and can do it at a much lower cost. we've had discussions with some of the manufacturers in india, and we have the ip for that candidate, then we would love to partner with them, and to all the third support organizations that exist, anxious awaiting an effective hiv vaccine that that they can include in the program to bring to the world's poorest countries spent the resources tracking did i showed you what i described $829 invested annually, you would've missing something. or you are missing something on the site in the industries department through a finance perspective is limited.

about 30 million is from the private sector companies are not actively engaged in the process. the follow-up to the time to we talked about is based, a prime boost, major vexing company to boost being studied coming from other large pharma companies. they are investing time and resources and opportunity and some money by the lion's share of investment coming from the gates foundation to win the vexing we hope shows efficacy, the question will not only be -- very much for the funds, public sector and philanthropic who have both been put this is a public good. it's not the son and to the point of the original polio vaccine but certainly we would expect given alliance shares of this product develop cost is being borne by public sector that there should be an equitable and very fair price for it.

>> and we get into license agreements we make sure that is part of the license agreement. >> cut at another point about some of the recent successes? they have been able to bring out some of the newer vaccines including rotavirus vaccine and the hpv vaccine. at prices under $5 per dose for an hpv vaccine, and under $3 per dose for a rotavirus vaccine. so some of the additional modeling work which would be happy to share off-line and be putting it on our website as soon as we finalize the slide open more. but we look at the cost per regiment in that range and including implementation cost about $30 per regiment. i'm no modeling expert, ever look at whether that we hit the bars that policymakers would consider cost effective, very

cost effective in low and middle income countries. if we are able to hit that bar, we do hit a very cost effective regiment and those are the cost that we then model. we need the right licensing agreement, if there is a for-profit company who gets involved, but like the strategy that i put in place at merck and so my colleagues and of the vexing countries put in place, we had tiered pricing to at merck is in no profit pricing strategy and about is sitting under $5 for hpv vaccine was because of that. other countries don't use that terminology but the lowest price for most income countries, pretty close, just cover your manufacturing costs i believe. if there is an arrangement or licensing deal with the manufacturer you would expect it would be stating that tiered pricing. in order for them to take on the program to bring an end to the world's poorest countries it has to hit that bar. i know seth berkley who was the

founder of iavi negotiates very hard to get those prices down as low as possible. >> thank you very much. market mccluskey from usaid. to first -- to quick question. used in the mr. of interest in seeing africa lead the way in the future hiv technology dignity to share your vision a little bit about how iavi has and will engage africa in that endeavor. but first i wanted, dr. fauci, could you mention have these antibodies can probably neutralize at the possible use and the potential expense having to do with acid antibody transfer? >> passive antibody transfer is being done right now as a proof of concept to determine what the level and with the breath of what you would need when you induce it. we know in animal models if you

passively transfer antibodies you can not only treat but you can prevent infections. spin can you explain -- >> that means take antibodies, cloned them and they go bunch of them, and you infuse them into someone, either to prevent them from getting infected or if they are infected to treat. it isn't a particularly good approach to treatment because we have one pill of three drugs i can do a much better than any antibody can do it. but it's been considered in clinical trials now for prevention, mainly that if you can get long acting antibodies and give it intramuscular once every three or four months you could have a pretty good protection. but the studies that are ongoing right are trying to determine what level of antibody do need to actually have protection? because then you can gauge what you need to induce with your vaccine breadth, depth and durability. >> is there any discussion about a level of antibody that would

prevent infection? i was reading through the lines of some of your slides and i didn't see much representing and controlling infection. >> no, no. as far as antibody goes, the goal is to prevent, not to control. t cells control. antibodies prevent. >> we have been involved in africa for 11, 12 years now and we've seen tremendous growth and intellectual capacity of contributing to the science, and we're really trying to build upon that momentum that's been established. and our principal investigators at each of the sides were involved in anti-very well educated, very well-trained professionals. they don't want simply to be a receptacle to vaccine coming out of the u.s. or europe and they will test it in their population

but they have a lot of insights, a lot of capabilities that they can contribute towards identifying what are the essential components of the vaccine. some of this work have been done at a smaller scale before. some of the epidemiology work, some of the marketing the course of an acute infection can identify what are the in and components that yield a better response and how does that vary depending upon the quake of the virus that they're exposed to. we have a program going on right now which is consultation with many of these investigators in africa and other partners that we have around the world where we are looking to build further on that, looking to plce even more studies in these sites to increase the learning, as well as to increase the training. not by building a new training program. we've trained a lot on good clinical practices, good laboratory practices, hundreds of employees throughout africa at our sites as well as other

sites have been trained, and mitchell's organization has been called, good for to sport practices in clinical trials. but looking to take up for the, can we help with some of the program to education. we're not going to set up a program. that's not our expertise but some of universities who have, how can we do that so that we can further evolve the scientific career of this talent and keep them there importantly within africa. the last entry i will mention is also for these investigators to be able to submit proposals that they will be a scientific review board that will pick the most compelling proposal. they have great ideas and additional scientific experiments that should be done that they can do within their centers. and so that program is being launched this year as well. >> dr. fauci, you've worked a lot to develop partnerships with institutions that are in africa and asia trying to build some skill sets. involved in some of his work. what are you doing to try to

build the engagement of some the researchers from the south are going to be critically impacted by the development of vexing? >> as part of our funding strategy, we always added degree of building a sustainable infrastructure. we start a trial or expand our clinical trial networks to south african or to uganda, to southeast asia. we always do it with the intent that when we leave there'll be able to do it themselves. so it is a parachute science. we go in and what. but we been doing that for some years right now but, in fact, we have our clinical trials network both vaccine, prevention, aye besides and others that is totally international now in southeast asia, in southern africa, in south america and the caribbean. at the end of the cape town

meeting where they were five days of very intense scientific presentations, so instead of instead it was over 30% of the presenters were from africa. something everything that tony talked about, we are doing at iavi, all of that has contributed to building the expertise spent major, you've worked a lot through avac. supportive of and also holding to account the research that's going on. how is that going? >> it's going well. it's hard. this is hard stuff. running clinical trials it's not easy and it's not for the faint of heart whether you are an investor or supporting research. one of those exciting parts took place in south africa the first time ever of this combined meeting, and that was done quite strategically because the prevention research world outside of the u.s., the infrastructure and the leadership coming from south africa is unparalleled. that has shown through quite a

lot the the community is deeply engaged. that is a surprising given when you look back at the history of epidemic through the action campaigns with extensive from an axis perspective but we're beginning to see in a partnership the same advocacy support. what's interesting is are the ones an aids vaccine. that's the easy part. the challenge is how do we ensure there's a responsiveness in what's happening scientifically on the ground? people not only want an aids vaccine and dana the research is happening but they are saying what about improvement in trials in south africa were? where is the access to prep? really is a question of how do you really inspire and develop the trust in the research enterprise writ large, not just your vaccine or microbicides but how do you build a relationship so that unity both supports science but has expectation, reasonable expectation of what science should be able to

deliver. >> a question over here. >> this kind of touches on what you were saying, mitchell. what you think will be the threshold for accuracy for a vaccine, are we going to be looking at the syllable or looking at a 50% efficacious vaccine that combined with prep or male circumcision gets us to the 100%? how do you communicate that effectively within a committee that years vaccine and thinks it's the one of% effective silver bullet? >> before you enter that i will ask you also, i think somebody gets in fact is about combination prevention. as you do clinical research we have all these other interventions which either individually or together start to result in a pretty high level of preventive benefits, how do you find a 50 or 60% effective vaccine? does it get hidden behind these other interventions? i would love to see them search

for silver bullet arm magic bullet stop the if we are searching for silver bullet we should pack up and go for something else. that's a realistic attitude. i don't -- we do know from the time truck, 31% efficacy, the regulars in thailand with a celtic boys were clear that that wasn't good enough. the number often bandied about is 50% but every agency would make a decision based on risk and benefit. we use that someone as the lowest level. i think this is your combination plays out in two ways. i was saying the clinical cows will be complicated, we hope they are complex by the fact is that the background and prevention would reduce the level of incidents of new infections. a vaccine would have to work harder but it wouldn't have to work, it doesn't have to be perfect because the number of infections to prevent is lower. the other interesting thing, the presentation and kept down, a

novel chomping in combination we talk about a vaccine which two different injections but i try was present from a couple of monkeys and the always fascinating. we are not here to prevent an infection in monkeys. we are here to stop an infection in humans. but in the small monkey trial a combination of a microbicide with a vaccine in the monkeys were shown to be much more effective than a little but it doesn't tell us, we've assumed just as a combination of treatment being the most effective treatment, combination prevention is what we will work towards the weather that is licensed by a combination or the introduction of a 50% effective vaccine when the rest of the prevention package has risen. we do not have to be perfect to be good enough. i think that's the take-home from my perspective. >> so 31 is not good enough but we will never get 95.

it will be somewhere between the two. i agree with mitchell that i will take 50. i really would like to see 60. i don't think there's going to be any trouble improving a vaccine is that percent because even though we know we have combination prevention, the issue of human nature and lack of adherence to that. so you have to pick out a highly at risk population. you have the ethical obligation to offer them things like prep, and like microbicides, et cetera, et cetera. but at the end of the human nature is going to win over and there's going to be people who will get infected, and hopefully you'll get enough people in the study of you can show that a vaccine works. >> i will be a little controversial coming from a background of introducing other vaccines and looking at the barriers to vaccine adoptions. so introduced hpv vaccine, had

100% efficacy, the four strains of included but the most commonly, most common strains out there, and i was able within the united states, and insured population, private insurance or covered 18 another by the vaccine for insurance program, to only get uptake of the three dose regimen in less than 40% of teenage girls. a lot of barriers we all know about anti-vaccine groups, it's more of an issue in developed countries but i think we will see it in some of the developing countries as well. i think we need to strive for 65%, 70%. i would hate to go to market with a vaccine that was 50% effective the i think you of all sorts of various put up, not the least of which is cost effectiveness. we ran senators on that when it talked about hitting that cost effective barrier or target that you need to reach. e. field or the efficacy and anything below 60%, he have lost

cost-effectiveness. your policymakers and your payers, there might be exceptions, such a high risk population that when you just immunize that population, maybe 50% is good enough, and combined with other approaches. but i think to get global uptake of a vaccine, widespread acceptance of a vaccine, we have to push the envelope. maybe we come out with something that isn't more 50-50% -- 50-60%. >> let me tell you a population that if i had 50% taxing i would vaccinate them all in a microsecond. if you go to the district in south africa and look at pregnant women between the ages of 23-25, they have a 44% prevalence of hiv infection. so i will take that 50% taxing and i will give it so fast your

eyes will turn. >> i will agree with you on that. >> heidi, he ha have been to tht region in south africa. we were there together. so one of the questions that will come out of this is, who pays for all this? the global fund went for replenishment not too long ago and got 12 billion, or less than 12 billion figure was trying to get 15. pepfar has not seen -- if you start accreting these different things on how do we do that? or do we have to do, focus on least in the interim while we're waiting for the money to go back up? these hotspot areas. it would try to find these can population with intervention may be makes more sense and credited everywhere at the same time? >> see, i disagree. i think if we get a vaccine, and i agree with margie that 50% is good for that region that 50% is not good or vaccinating everybody who hasn't a they might be infected.

cost-effectiveness is not good enough. if we get a vaccine that lets is 60% effective, i don't think we will have a problem in getting that paid for, to be quite honest with you. because the cost-effectiveness of preventing an infection versus lifelong antiretroviral therapy issued. i think you'll get world bank, gates foundation, u.s. government, you know, you get a lot of groups that will take that. a lot of things keeping up at night. that doesn't. that's not one of them. >> we use this turn combination prevention and it's a lovely term. they often get mangled. it's not throwing the kitchen sink at everyone all the time to i think we were looking at, your point, a lot of talk about hotspot until we epidemic is and i think we're getting hopefully much smart as a committee to get rid we need to be with which intervention at which time in which placed the they will be

different but i think we need to be clear about that because we are going to see plot lines and that is the new normal. let's hope it doesn't go down from there. weekly have to be more efficient whether it's the r&d expenditure or in the delivered expenditure, pepfar, global fund. even in the coming years how do we take the tools we have and ensure the reaching right people and the right time and place for not throwing things scattershot. >> hi. this may be a sneak preview for next talk, dr. fauci, but how does the reemergence of ebola and its attendant hysteria in this country, some i characterize it, how does that compare with the early hiv scare in haiti, in san francisco and central africa when there wasn't even a name for it?

part two is how will ebola, how you be competing with ebola on funding? you talk about your flat-lining funding levels. and three, either because of skill in the field for public awareness campaigns for both conditions of? >> so i will take the first one. did you go back to the very early '80s, you are having the evolution of what turned out to be an incredibly historic epidemic, pandemic. and relatively few people paid attention to it. and now you have two americans who have been infected with ebola, both of them directly and overtly and in a self-sacrificing way cared for and ebola patient. those are the only two people who have gotten infected in the united states.

and we have this overwhelming attention and fear to it. so it would have been nice, retrospectively, if back in the 1980s when i was saying, hey, we have a real problem here, you probably have more infections and you can possibly imagine, that we would've had as much concerned back in the 1980s for hiv as we are having for ebola right now applause but. >> -- [applause]

yesterday 5700 people were infeh

aids. one day, okay? compare that to what's going on right now with ebola and the amount of attenáion and concern that there is. i'm not downplaying or denigrating at all the concern you have about a very serious disease. t when you think about the magnitude and how the public gets immune to that, you know, every single day 4100 people die of aids, every single day. and you get kind of numb to that. and it's not the thing that's a getting people excited. so you try to when you want to really put attention on things that really need more attention, you could say, you know, folks, take a look at this. we have this ongoing problem. take a look at malaria, tuberculosis. so i use the attention that we're getting with ebola, people say, you know, we'rq getting all this attention. how about the same sort of sustained attention for other great killers? >> there was another part to the

question which was sort of the ability to sort of do publrc information campaigns, the economies of scale we're actually to maybe at least in terms of basic capacity building, safe practices in hospitals. is there something we're doing that's trying to leverage information around ebola to help with hiv risk? really is a different animal? >> it's a different ball game. >> geographically to remember where ebola is and hiv is and the three countries affected by ebola are not major indem cantic hiv communities -- endemic hiv communities. i was struck by the nigerian response and at least as it's describedñr building on platfor, both the pepfar engagements in nigeria allowed to get them very quickly to get on top of the epidemic or what could have been an epidemr(y obviously, an ebola epidemic in

nigeria would have made things far, far more dramatic in terms of numbers. and it tells me that health systems matter. again, we know that. but functioning health systems work. and irz proudly from omaha, nebraska, prouder now over the last couple of months to watch the clinic in omaha. health systems matter, and we've underinvested there, and it's going to make a big difference when we have any intervention, having a health system that can deliver is critical. think the leveraging for me don't say we're not going to invest in pepfar because we have an ebola outbreak. we should be doubling down because it's, in my mind, the best investment in the history of global public health, in fact. so i think we need to be seeing it in that regard. >> great. paul? >> mitchell, you gave voice to defense against ebola in nigeria

where it could have been incredibly explosive is largely donor-funded, pepfar-funded labs and things like this. hear informally from then, we administration, oh, well, you @% know, we're not sure -- we're going to have to put money into ebola this coming year and so, you know, stop pestering us about pepfar. actually, the vice president said that in, you know, in response to a question and answer period in boston which was ther unfortunate. so members of co'gress are talking a whole lot right now about an emergency supplemental which we haven't seen for global public health for years and years and years, but the department of defense has freed up $1 billion to go and do important work. this is the lord's work. it's good that dod is constructing clinics and so forth. but there's not exactly a shortage of funding at the moment. nonetheless, members of congres% are talking about doing

emergency supplementals so they can put their stamp on it. it's the psalm members of congress that -- the same members of congress that wq)e all doing a year-long grind for $300 million for pepfar after $6 million in cuts -- 600 million in cuts. that's not really a question. [laughter] thereráhp lot of momentum around health systems and ebola and viruses, and that's important, but we need to capture -- thanks for what you were saying, that's all on that grindstone. >> yeah. i think we're really hoping that margie's right and we get an hiv vaccine while you're still in office. as confident as you are, certainly, it's easy to start trading one thing off for another. and what i hear you saying is that we need to add on top of "ppá we're already doing the cost of potentially getting an hiv vaccine out, and that is going to mean more in terms of financing. that case has to be made.

to do this session which is to help people like heidi who have to go back to the hr&l and explain these things, understand that, v it will offer great opportunity, in fact, we're going to have to invest to achieve those savings. and that's a hard argument to make in this city particularly when it comes to aid. final questions, and we'll close out for the day. great. so i want to thank our panelists for coming here. dr. fauci, thankáh#or leading off the series, thrilled to have you here, as always. thanks for your work on this. get back to the other virus. [laughter] mitchell, thank you very much for coming and sharing the views of civil society. margie, thank you for coming on behalf of aiabai. we are looking for feedback at csis on future events like this, so if you have ideas particularly around this technology thing, we're happy to

hear them. carl, we're looking for e-mails from you. thank you for coming, have a good afternoon and don't forget to vote. [applause] [inaudible conversations] >> well, the obama administration today opened up access for consumers to view and price out health insurance plans on the healthcare.gov web site. although the open enrollment period to purchase plans doesn't begin until this saturday. coming up in just an hour, health and human services secretary sylvia burwell will talk about her department's efforts in insuring the readiness of the web site. see her remarks at one p.m. eastern on our companion network, c-span. and president obama arriving weeklong trip to the asia-pacific region. the president starting his trip in china for an economic cooperation forum today, announced that two countries have agreed to expand áheir visa

program beyond the current one-year term. on wednesday the president will meet with chinese president xi jinping, thursday and friday in myanmar for more economic meetings, also holding separate meetings with the burmese president and opposition leader. he'll then head to australia this weekend for the g20 summit where he's expected to conclude his trip with p major policy address. yahoo! back here in washington -- back here in washington, the house and senate will return. the house is back on wednesday for debate on ten bills including updating the presidential records act. the house republican conference has scheduled leadership elections for thursday, and democrats are reportedly set to hold theirs on november 18th. the senate returns l wednesday with votes on judicial nominations, a child care development block grant program. both parties will hold leadership elections on thursday. you can see the house on c-span, the senate right here on "p> tonight on "the

communicators," christopher yoo, professor at the university of pennsylvania law school and director of its center for technology, innovation and competition. >> people who oppose prioritization should take a look at the r'ternet header, the ipv foreheader. that is the magic that makes the internet work. there's something called the type of service flag. that's different service classes really for high bandwidth services, low latency services, different forms of prioritization. that was designed for the internet from the beginning. people say, oh, that's just an old artifact. they not only kept that field, they actually included another field called label field to do another form of prioritization quality service. õáz if you look at the engineering design to suggest that this was never intended, prioritization was never intended to be allowed, i think a little engineering knowledge goes a lont way. it's a design feature of the network from the beginning, and

if you talk to the way people are actually using the network, they're using it today to deliver, for example, voice services. we've all called on skype and been fruáu)ated. the true, completely ip-based voice service to your phone is called voiceover lte. all uses prioritization. the only way to make the call quality work and a lot of video and other things work the same way. >> tonight an eight eastern on "the communicators" on c-span2. >> well, the chief of naval operations discussed the future of maritime strategy including the ongoing rebalance to the asia-pacific region. admiral jonathan greenert spoke at a' event hosted by the brookings institution here in washington. this is about an hour. >> good morning, everyone. welcome to brookings. i'm mike o'hanlon with the defense center here, the suspect on 21st century intelligence, and we're honored to have

admiral jonathan greenert, the navy's top leader, and he will be speaking this morning for a few minutes about trends in the navy and strategic thinking, all of what he's up to around the world including, of course, the rebalance to the asia-pacific and other topics of interest. after that we'll hp+e a bit of a conversation up here before going to you. i just wanted to say a couple of words of appreciation and biography about admiral greenert. he's a native of pennsylvania, i believe a quarterback country as we say, so maybe we should get you into the mix on saving the redskins as well as all the other things you're doing aroun" the world. a 1975 graduate of annapolis, a submariner by profession, has commanded attack submarines as well as ballistic missile submarines, was commander of the u.s. seventh fleet among various other jobs, was a major part of the planning and the so-called nh shop of the navy as well as prior to his current position as the chief of naval operations. he's been in that position now about three years which makes

him part of a remarkable class of joint chiefs who came into office in that year. admiral greenert is joined by general odierno and general dempsey, among others, as now three-year veterans of the joint chiefs. and so r would like to begin the speculation or at least the (ur-ájttáj that i hope he may be considered for yet another four-star job when general dempsey steps down next year, but i don't need to do the admiral a disservice by interjecting that too much into the conversation. i would just say in the three years he's been at the helm of the navy, he has been associated with a number of major initipáives including, of course, the so-called rebalance to the asia-pacific and much of the thinking around air-sea battle, a topic i'm sure will come u( today. without further ado, please join me in welcoming admiral greenert to brookings. >> thanks, mike.% thank you very much. [applause] thank you. you're very kind.

in fact, i was in pennsylvania yesterday. we were talking about -- i visited a high school and it was called moon township, and it's enormous. big school, had the intermediate school there, and we were talking to the high school students about pretty much what we're going to talk about today. and their interest and their in-depth knowledge of world affairs totally stunned me. i was taken back by it. i figured they'd want to talk about local stuff or this or that or why the navy and all this business. boom, they were way out there, and they said how do we get information beyond just the headlines? we would like to understand our world today. we talked a little bit about, of course, our world today is not going to be their world as we've seen that remarkable evolution, and they have a partner online that we were vtcing with in taiwan, a partner high school. so we got worldwide very quickly. we had a q&a session, and they were remarkably involved. so it is an amazing world as we get out there, how connected we

are. i'd like to talk briefly about our maritime strategy and why we are redoing that. the asia-pacific rebalance, as michael said, how we're moving on in that and our relations with, in this case, the chinese navy. it's kind of an update on thr'gs. we've had the international sea power symposium now about six weeks ago, and we are continuing the evolution as directed by the president and in accordance with our rebalance to the asia-pacific. but our maritime strategy, i hope and expect that by the end of this calendar year we'll be publishing this. we have a relatively new congressman about the of the coast guard -- commandant of the coast guard, and i need to give them time to digest what we have put together and make sure that we're in sync because this is a sea services document; navy, marine corps and coast guard. the cáujjt reasons for the revision -- and it pretty much is a revision -- is that, obviously, the security and fiscal changes since 2007, they've been extraordinary.

the indian ocean ty asia region, the changes, the anti-access air denial and the need for access, energy, the challenge for energy and the need for energy, anti-terrorism, maritime disputes, all of these have dramatically evolved since 2007. we have a new strategy since then, the defense strategic guidance 2012, a qdr and homeland security where the coast guard resides has had a homeland security review. so all of these really compel us and dictate a change to our strategy. our principles will be the same, the value of presence to be where it matters, when it matters as a sea service. the three of us and how we fit into that. and the value of maritime networks as the leverage and the strength that you get out of maritime networks will come out in that. we'll address the sea services functions of deterrence, power projection, sea control,

maritime security and the importance of access. but, you know, if you could put up one of the graphic hq)e, the slide, if you wonder the evolving world -- compare this to 2010, and i ask -- 2007, and i ask you, there's only a few photos up here. you hey, i remember the same identification in 2007. it's different. we had a surge going on in iraq, and the evolving war-fighting challenges since then in cyber, electronic warfare, electronic attack, the electromagnetic spectrum, if you will, weapons of mass destruction and, of course, in the case of syria, chemical weapons that have evolved since then in counterterrorism. so our objective is by the end of the year we'll complete and "p$ave this thing published. a little bit on the asia-pacific rebalance. some folks say, well, is that thing really going to happen?

are you still going to do that? i say, yes. despite current events, the long-range interests of your navy and really of your security posture, the department of defense, is in the asia-pacific. to review, over 50% of the world's shipping tonnage pass through the straits of malacca, sun da and lumbar. that's just down there in the end nice area in southeast asia. and half of the liquid natural gas moves through the south china sea. five of the top fifteen trading partners are in the region, asia-pacific. five of our seven security treaties are in the region. "páy and also to refresh, we hae been engaged over 70 years in the asia-pacific region and with presence, with significant presence in that area. we will continue with this rebalance. and that rebalance means, to refresh, forçó us properly postured forward forces.

and we are on track with destroyers to japan, forward @&% deployed naval force, littoral combat ships to singapore, new attacks -- excuse me, a submarine to guam, the trion the which is our maritime surveillance to deploy that out of guam and okinawa, our p8a, our maritime patrol aircraft. we are now in our third deployment out there. that will contr'ue to evolve. most of you saw yesterday the landing on the nimitz of the #35c, the joint strike fighter. so as that is bringing that in, evolves, we will also forward deploy that first to the asia-pacific. it's advanced capabilities in the pacific area of responsibility is our benchmark and retains that. but it's also understanding -- and that means, you can call it intellq(uup& capacity, you can call it increased engagement with allies, partners and potential partners such as china

and india. the rebalance is not single not just about china, but it is china's, certainly, one part of it and a very important part of it. china and our country are the world's largest economies, and we are, frankly, intertwined. you know that. number two trading partner, the number three export market and our number one um port source. -- import source is china. the mutual prosperity of both of us is in our collective best interests. our presidents met about 18 months ago and recognized and told us we've got to get the relationship right. and we are continuing on that track. in the navy it was about finding out and working out what are the differences and how do we increase cooperation. we acknowledge the i growing influence -- the growing influence and size of the chinese navy, but we agree and we consist that we have a consistent applicatron of the international laws and norms,

that we acá responsibly both locally and globally. of you are familiar with and our rules of behavior working group which has been in progress meeting periodically, about monthly now. these are folks made up of our defense and the ministry of defense in china and, of course, our naval officers and their naval officers working on rules of behavior in a wo)king group. and to contribute to the international order and security. in other words, to be a leader. and we talked about that. "we," would be the admiral in (rr'a, myself here in newport about six weeks ago with his party and my group, and we talked about it with the heads of navy. how do we continue the useful dialogue that we need to make sure we have a governance on the high seas? so both our presidents directe" the strength for military ties and to build the understanding. and as president obama said, we should institutionalize and regularize our discussions that take place.

the navies are well suited to the task. we are f)equently encountering each other in an international domain, the high seas. we encounter each other routinely out there in the global commons. and in a vast arqpwe are often called together to cooperate on areas of shared challenges; humanitarian assistance, disaster relief, typhoons, tsunamis, volcanos, that ring of counterpiracy, you're familiar with that, and not long ago we met to search for that missing malaysian aircraft. so a little update on our relationship, how are things coming together? well, we're working from the top down, that's myself and the chinese admiral, but p&so from the bottom up as we've encouraged and set up our folks to get together at kind of mid-grade officer level and senior officer.

met u)u$ admiral wu five times in the last year, and we're working on counterpart visits here in 2015. we will put our input into -- i will provide my input to the folks down in policy in the office of the secretary of defense, and i'll talk about a little bit more on the junior interactions here in just a minute. the fact is with this rising navy in china, we have, in my view, opportunity. the c$allenge is to get rid of needless, unfounded, unprofessional cases in this interaction that we are ultimately, inevitably going to have at sea. i'm talking about unsafe operations. you're familiar with many of recently in our sensitive reconnaissance operation intercepts. we've had nothing recent, no unsafe or untoward incidents since august when we hp" this last sro intercept that we viewed as unsafe, and we dehalved and talked about that. admiral wu and i talked about

this at length a'd where we might go ahead when we met six weeks ago in newport. there's a concern that when we go to sea, as we meet at sea, that we have deliberate governance with proper protocols and really decrease the potential for miscalculation. history is full of cases of miscalculation causing nations to put, putting them in a situation that they don't want to be in and leaving them no recourse. we need the clear standards of behavior to make sure we have consistent, professional operations in international waters and in international air space. and, again, this was embraced by all thq heads of navy and the international sea power symposium not long ago. we started down this road in, i think, a pretty robust manner back in april of this year at the western pacific naval symposium when we got together voluntarily, 22 navies, embraced professio'al behavior and clear

communications. we exercise it at rimpac where we had 25 navies there, 42 ships, and we worked on that at rimpac. a lot of different nations, a lot of different navies. but this will be a long, deliberate process nqq"ing constant attention. we're bringing new officers in all the time. in some cases for some navies, it's very different to have an engagement, to be open and to be conversing out there at sea. in the july counterpart visit that i had where i went to china at the invitation of admiral wu, i visited what's called the state oceanic administration. i would call that sort of analogous to our d. of homeland security -- our de(artment of homeland security. that's where their coast guard, if you will, is located. and we talked about introducing the option or the protocol to the coast guard. and it was absorbed, it was taken in as something t$at was viable. our coast guard is very

ãinterested in it, we're making that connection now to continue to expand. in newport we discussed expansion across the globe with all of the nations, and it was pretty much embraced by all of the coast guards and navies around the world as something that has value, maybe not in its current precise format, but the concept of a code, a known protocol at sea was embraced globally. the conversation doesn't stop. we need the sustained dialogue, and we had our sea power symposium, as i mentioned over and over again, here six weeks ago. these symposia will continue. we have the next larger one in singapore next may, and we'll continue the discussion on both cyber at sea and the impact there and, of course, how do we continue to expand and go beyond that. bilaterally, admiral wu and i agreed to continue on. we kind of synchronized on where we are in the six initiatives that we started, actually,

almost 15 months ago, whenever he was here in the united states. and they are to continue fleqás training in and the promotion of quis between the two of us. we both agree it's a good initiative, to increase port visits and outbring next -- again, to my boss -- next year's proposals later this month for next year. i'll bring those proposals repo)t visits. we agreed to establish regular service chief communications and the means to do that. we agreed to increase our academic exchanges both at our naval war college and naval academies, and those are in process. admiral wu brought respective commanding officers up to newport where they talked to our teachers, admiral wu attended and synchronized that, and is we did that. they're coming over here to the united states. we're working through the visas and bringing that up where some of his pcos will come over and continue that exchange.

we agreed to put together a working group for human resources as he is moving to build his navy of the future, and we're building our navy of the future to go over those challenges. and then lastly, to work on preapproved exercises. my pacific fleet commander is working with his requisite counterpart to find out how do we put modules together so that when we meet at sea and we have that opportunity whether we're doing counterpiracy operations down in the south china sea, working in the east china sea, how can we do exercises, simple exercises that have -- thaá we can get preapproved? so it's about building "p(jjt)qq'ce and understanding throughout the ranks, to continue on that road. so let me close now and then we'll get into your questions and answers and, michael, we'll have a conversation. we're committed to the security of the asia-pacific. the alliances are strong, and we will honor our treaties. the engagement is increasing both bilaterally andñi multilaterally, and it's really

part of that rebalance. but relationships that i spoke to both with the people's republic of china, their navy, and india which is becoming an increasing opportunity will not be at the expense of our allies. it's not zero sum. international norms and standards will benefit the region, and we need to continue on that way ahead. so thanks a lot, and i look forward to your questions. [applause] >> thank you, admiral, for those great remarks and for what you're doing operationally and planning the future navy and in working with allies and with the chinese. i wanted to begin with the chinese navy and ask you to give us a little bit of your assessment, an update as to their quality. i remember admiral willard when he was running pacific command a few years ago made the statement, very pithy statement, that everything we thought áhe chinese might do they're actually doing even faster and better than we once thought. and, of course, the flipside of

everything you discussed in terms of trying to build engagement is our concern about their rise and their potential capability. how do you assess thqr) overall capacity and quality at this juncture? >> well, i put it into two categories maybe. one, the three-dimensional, the construction, the technology and all that. i think admiral willard has it about right. i don't know that they're continuing that speed that he mentioned before. i would call it apace with what "p"evelopment, architecture, if you will, naval architecture and the building they're in. i would say that what we find in rimpac, they've operated among or in among themselves but not internationally. so i think they have a pretty good learning curve to take on. we saw it in rimpac. they started out sort of rudimentary q,ercises, had some problems maybe here and there. not unexpected for somebody entering into a multilateral engagement. but they ramped up reasonably well.

so they have, we have it's kind of like almost an olympic "pq,ercises we have. how do we do in the gun shoot, how do we do in this and that? some say, well, they were average to high average. well, okay, i don't know what judges decided that. i would say they're coming along well, especially their interest in humanitarian assistance disaster relief. and that's oar do and to take on -- and to take on the responsible role that a growing navy would take on. >> are you overly concerned about the pace at which they're getting better? the last thing you said seems fairly apple pie if they're helping with humanitarian operations and so forth. i know our navies have sometimes come into close proximity, there have been some dangerous @&c% encounters. they're not entirely comfortable with our presence in the western (acific. there's a lot of thinking they want to push us back. i guess a twofold question, are you particularly worried about that and, secondly, do we need