Sharon Hillier: [00:00:00] Well, it's really a great pleasure. I'm honored to be here. I'm not a basic scientist. I'm not a retrovirologist. I don't discover drugs. But what we have done is actually used small molecules, antiretrovirals, to actually prevent HIV. That's really going to be a quick summary of that field. Everyone has already told a little bit about themselves, and I'm no different. I was born in a [00:00:30] small dairy town like my good friend Paul [Volberding], but I was born in the same little town as Merle Sande (1939–2007). We oftentimes laughed with each other about how the two of us ever managed to get out of Mount Vernon in Washington and end up doing what we did.
I graduated in a very strange way with a degree in bacteriology and in public health. I suppose that very movement actually is what launched me on this path of both doing fundamental work [00:01:00] as well as with a very public health focus. I moved to Seattle after my doctorate in 1982 and began my career. I switched from my basic research, which was in the intermediary metabolism of Yersinia pestis bubonic plague to sexually transmitted infections, which are continuing to be the plague that we feel.
My children, I have two who are now 23 and 26, were endlessly and remain endlessly [00:01:30] embarrassed by what I do. My daughter Louise once explained to her fourth-grade teacher when they asked, "What is your mother doing?" I thought it was perfect. She said, “My mother works on the kinds of infections nobody wants to get and almost nobody wants to talk about." I think that pretty much summarizes my life. I think yesterday I was texting with her, she's off interviewing for postdocs, and I said, “Well, I'm here at Cold Spring Harbor listening to some really exciting fundamental [00:02:00] biology.” She said, “Don't worry Mom, you can still talk about vaginas tomorrow," so here I am.
Following my doctoral work, actually before I became involved in clinical trials, I began to do some early work in which women were susceptible and what made women more susceptible to HIV, with collaborators like King Holmes and Joan Kreiss and David Clemetson, and others. We found really early [00:02:30] that cervical ectopy changes HIV transmission in Kenyan couples, and that women with inflammation have a greater capacity to shed virus. (1, 2, 3) We found that, first in 1995, we reported, in Thai sex workers that women with abnormal vaginal microbiota or bacterial vaginosis were four times more likely to acquire HIV. (4) So that's something we did 20 years ago. We did some early work associating vaginal [00:03:00] douching in African women with HIV risk, and showed that women who had a non-lactobacillus dominant microbiota had an increased acquisition of HIV. (5) That was in collaboration with the Rakai [Project] folks. We also, really I think we were the first to describe lactobacilli that make or produce hydrogen peroxide decreased woman's risk of HIV twofold. (6, 7)
I think that [00:03:30] set a perfect stage for what I have been doing the past 20 years, which is working in HIV prevention trials. When you look at the past 10 years, it's a stunning array of successful and not so successful prevention trials. It's almost breathtaking how much work has come out. Following the three successful circumcision studies—circumcision, which has hardly been mentioned at this meeting, but which has been rolled out broadly now [00:04:00] in sub-Saharan Africa, and which we know, with a one-off procedure, can reduce HIV risk by 50%. We had a total of eight oral PrEP studies with wildly different results, three studies of tenofovir gel, the HPTN 052 study of treatment-as-prevention, which has been mentioned several times, and the two vaginal ring studies.
Where are we today with HIV prevention, biomedical prevention using small [00:04:30] molecules? Well, as I mentioned there have been eight oral tenofovir based studies, and six of those eight showed a reduction in HIV. Now there are many demonstration projects underway. It's being rolled out as part of the PrEP program. I know Bob Redfield will get to that a little bit later today. There were the three completed studies of tenofovir gel with one of three positive. Two completed studies of the dapivirine vaginal ring which were both reported at CROI this year. [00:05:00] We've seen our first studies of maraviroc alone, and in combination with tenofovir based regimens for PrEP by the HPTN 069 (2012–2016) team, and presented at CROI (Conference on Retroviruses and Opportunistic Infections) this year. (8) The first studies of tenofovir gel as a rectal microbicide this year. And we're beginning to see the first integrase inhibitors as injectables and as vaginal rings. Finally, we're seeing this idea which is an old one but a really good one of combining antiretroviral [00:05:30] drugs with hormonal contraceptives to make multi-purpose products that could meet multiple needs for women.
Let's just talk very, very briefly about some of the oral PrEP studies because I think there are some lessons that we really need to remember. When the first studies were reported, The initial iPrEx (2007–2011) result was 44%, and everybody went "Hmm, that's not so good. Maybe it’s [00:06:00] good, but it could be much better." I think people didn't really get excited about oral PrEP until they saw, in the later studies the promise, the high levels of efficacy that were observed. In the IPERGAY study (2012–2015), what they saw were that in this study after we knew that PrEP could work that 414 men were we instructed to use the product oral Truvada (FTC+tenofovir) or placebo at the time of sex and another dose after. (9) What they found was that there was an 86% [00:06:30] reduction in HIV infection, which is pretty astonishing. The PROUD study (2012–2015) which was immediate versus deferred use of daily oral PrEP, they also saw an 86% reduction. (10) When those two studies were presented at CROI and published, I think what you saw was, suddenly, "Well PrEP can really work."
But why do we see these differences? There is very clear evidence that MSM using PrEP have a huge reduction in HIV [00:07:00] acquisition. But the highest level of reduction really has occurred in MSM who are in their middle to late 30s, who live in North America or Europe. That's not because Truvada doesn't work in African or South American people. (11) It has to do with adherence where we've seen problems or things like MSM who are young, less than 25 years of age. The studies that have been done to date, there have been [00:07:30] relatively few younger people, but in those studies, it was not significantly protective in young men. And it hasn't been protective in transgender women, again likely due to low adherence. We also see huge differences, I just mentioned, in region, with the PROUD and IPERGAY studies being done in Europe. The US studies showing good protection from oral PrEP, but showing much less protection of 40% efficacy in the iPrEx study in the Andean [00:08:00] region.
We see similar diversity in young women. Although oral-based tenofovir was very effective in serodiscordant couples, Connie Celum's beautiful partners-PrEP study, which was one of the two big studies that led to the licensure package for PrEP—we saw a 65% efficacy in the intent-to-treat analysis. (12) However, in the Fem-PrEP study (2009–2011) which was done in young women and average age [00:08:30] of 23, adherence to product was very low and it was stopped for futility. Absolutely, no efficacy. Similarly in the VOICE study (2009–2011), which was one that we were affiliated with, we also showed Truvada and tenofovir alone were not effective, because adherence to product was low. (13) Finally, with the tenofovir-based products that have been used in gel form, it's been a real mixed story. The first proof of concept that a topically applied product could be effective by [00:09:00] Salim Karim and his team in the CAPRISA 004 study (2007–2010) with a 39% efficacy with broad confidence intervals. (14) In the VOICE trial, we saw a 15% efficacy. Like in Salim's study, we saw about a 60% reduction in HIV in those who used it, but unfortunately a very small number who used it well. The FACTS study which was reported at CROI in 2015 and led by Glenda Gray among others showing low adherence in an [00:09:30] overall efficacy of zero.
What that teaches you is you can utilize small molecules for prevention of HIV, but it's much easier to actually do the studies than it is to actually get people to use the products. I'm going to use that as a way to think about where we go in the future because for people who can use oral PrEP, it's magnificently effective. It's a really [00:10:00] great strategy. Based on the strength of the FDA approval in 2012, the WHO guidelines this year actually recommend that PrEP be provided for anyone living in areas where the incidence is in excess of 3% per year. (15) That has led to a huge movement by Gilead, and I think they are to be recognized for the great work they've done in trying to get regulatory approval of Truvada for PrEP [00:10:30] more broadly. So we see it now in Europe, interestingly the UK has been quite slow to roll it out even though one of the great studies was done there. But we're seeing it now at prices in South Africa, for example, for a month of PrEP about $3.50 with real scale-up. That's terrific. For people who can use it, it has been an amazing thing.
When we think about those first three studies of circumcision [00:11:00] and what that led to, and then the eight next studies of oral Truvada as PrEP, the lesson is it takes more than one study or two studies to actually tell the whole story. But now we are moving then to some of the newer products. I want to spend a few minutes on that, the vaginal rings, our sustained delivery products.
The idea of a vaginal ring was, essentially, it would be longer-lasting a sustained delivery method that's completely reversible, that [00:11:30] it would overcome any of the problems associated with daily adherence because the ring could just be placed into the vagina, left in place for a month at a time, that you wouldn't have a pill bottle to carry around so it would be incredibly discreet, and that it would have a magnificent safety profile because the amount of drug that comes out is quite low.
Janssen Pharmaceutical provided royalty-free license to the International Partnership for Microbicides which is a nonprofit group. [00:12:00] Essentially they developed this ring which slowly releases the ARV (antiretroviral) drug dapivirine as a non-nucleoside reverse transcriptase inhibitor (NNRTI). The entire dose over an entire month of use is 4mg, contrast that to 9gm of oral Truvada. It's actually a whisper of drug. In fact, many of us working in the field thought that so little drug, it's almost impossible to imagine it could actually work.
[00:12:30] 4,588 women were enrolled in four countries in two-phase three studies. They were called, not very innovatively, the Ring study and ASPIRE. You can see there how many clinical sites they were and where they were located in sub-Saharan Africa. The two studies were really designed to ask four questions. Can this ring containing such a minuscule amount of ARV prevent HIV [00:13:00] substantially? Is it safe? Is it acceptable to women and will they use it? Will it overcome some of the adherence problems?
It was found to be extraordinarily safe, absolutely no difference in the dapivirine and placebo groups and the numbers of adverse events. There just are absolutely no systemic events, no bone toxicity, no kidney toxicity. We didn't see any interactions between the NNRTI and contraceptives like levonorgestrel, we didn't see any [00:13:30] changes in the numbers of pregnancy. We saw no difference in the number of STIs. And importantly, we saw no significant HIV drug resistance although John Mellors' lab is still looking at some of the deep sequencing on all the seroconverters from the study.
What we saw overall was disappointing, at least to us, in that the overall efficacy in the initial intent to treat analysis was quite modest. It was about 30%. In the Ring study it was 31%, in the ASPIRE trial it was 27%. [00:14:00] Just doing a pre-specified, age-related efficacy look, what we found was that there was a 60% reduction in HIV among women greater than 25 years of age. In other words, some of the same kinds of challenges that we saw with oral PrEP were also a problem with the dapivirine ring.
So I'm going to talk about this a lot because trying to understand how well a product can work, I think [00:14:30]can help us understand whether or not it's worth trying to implement.
How do you figure out how well it worked? One of the problems we have with tenofovir gel was you really couldn't tell when women used it, or you could only tell in a very subjective way. But with the vaginal rings, what we got when women came back was they would bring the ring with them, hopefully still in the vagina. We would collect those rings, we send them to a laboratory [00:15:00] in South Africa called Parexel. They ground up the rings, they extracted the dapivirine, and they could tell how much had leached out. Lots of work was done to ensure that we knew that if the women soak the rings in tea or beer or whiskey or anything, that their drug didn't come out. It really is such a hydrophobic drug. You have to have it in the vaginal fluid for it to elute. Then what we did in this study is we collected [00:15:30] blood samples quarterly but we collected rings every month. Essentially then what we could do is go back and look at ring markers of adherence, that is to say how well women use the ring.
When we got all the rings back for the entire study. This is what the distribution looked like. What you can see is that initially, as I told you, the rings are loaded with about 25mg of drug and we expect about 4mg [00:16:00] to come out over a month of use. What you see here is that on average, we saw something like that 21mg, but there were a lot of women out here who essentially apparently didn't use the ring. So then what you can do is say, "Okay, if we see levels of, say, less than 22mg, that probably infers fairly reasonable adherence and people down here obviously had really terrific adherence, so sort of medium, [00:16:30] high adherence and non-adherence."
And so we did some time-varying analysis. I think these are actually quite important and they were reported by Elizabeth Brown from the Fred Hutchinson Cancer Research Center last summer. (16) Essentially what she did was use different models to actually look at how much drug was out of the rings we got from the women and looked at efficacy endpoints. To do this, she did risk reduction models using time-varying [00:17:00] Cox models with adherence based on residual drug level in the rings. Our outcome was the time to first detection of HIV. These were limited to the subset of women on whom we had rings and all the comparisons against the placebo arm. For example, when you're doing this study, it's complicated. Women don't always come back at 28 days. They might come in at 21 days or they might come in at 40 days. One of the things that we had to do [00:17:30] was take into account how long the ring had been in place. Then we had to go look at when seroconversion happened.
What we did was we looked at the rings that occurred in these two months before seroconversion. We know they were HIV negative here and then we looked at the rings that were there the three visits prior to seroconversion. What we found compared to controls was that in women who had no use [00:18:00] there was no reduction obviously but in the women who used it, the middle third or the top third—this is that level of 4mg coming out—you saw a 75% reduction. Obviously, this is a sub-analysis so it has broad confidence intervals. But across here what you see is the incidents decreasing from 5% to 2.7%, 1.6% to 1.2% compared to the 4.7% in that matched placebo group.
If we looked at the three months prior to seroconversion [00:18:30] we saw a very similar kind of trend with rapidly decreasing incidents and very similar kinds of incidents in the placebo and the non-use group. This is one of those sort of "doi" moments, ARVs work if you use them. But actually in a way it was quite earth shaking to us because what it means is that a whisper of ARV can work if you use it. [00:19:00]
And finally, did it work in young women if they used it? I think what we found is that the youngest women were the most likely to remove their rings, and the answer was yes, we saw very similar trends. Across multiple analysis, there's a statistically significant relationship between HIV use and protection. These results suggest that ring use is associated with at least a 50% reduction and maybe a 70% reduction when used consistently.
We also found [00:19:30] young women said it was empowering to use. My favorite quote is one I'll show here on the bottom. This is a young woman who was negotiating with her partner about using a condom. "No, I told him, "Take this ring as the condom." I said, "You do not want the condom. This is our condom. Just ignore it, it's inside my body and it's mine." We never had a problem about it and we never spoke about it again." In other words, this was a way that young women could actually use a product when they weren't able to negotiate [00:20:00] for condom use.
The ring is actually an open-label extension's now and when we think about the future or the near future if the ring is approved we're going to have essentially two options for prevention for women. The vaginal ring shown here in actual size against 30 days of a tenofovir-emtricitabine. What we think about is how might this work? How does it stack up? We're gonna require, of course, [00:20:30] HIV testing to ensure that people are not HIV infected for both oral PrEP or vaginal ring. As I mentioned the safety profile is fantastic for the vaginal ring because of the drug exposure is so long so it will not require creatinine testing. I think a downside for PrEP is that toxicity. For the vaginal ring it does not protect against anal sex, and I think that is a place for, if young women are having anal sex, and especially [00:21:00]sex workers who perform a lot of anal sex, I think the Dapivirine ring is not going to be for them. Finally, the fact that it can be inserted and left in place for a month does not require daily adherence and I think that is also a plus.
Just for the heck of it I went to the lab and actually weighed out nine grams of tenofovir. This is what it looks like just to help you visualize what a tiny speck of drug that really is. [00:21:30] When I think I think about that it's still amazing to me that that much apply topically can actually have such a substantial benefit.
People are really excited about PrEP by injection. I think you've heard a few times mentioned cabotegravir and rilpivirine which have completed phase II studies and we expect results very soon. People are really excited about the idea of using injectable integrase inhibitor like cabotegravir. [00:22:00] My understanding is that cabotegravir long-acting in MSM and PrEP study which is going to be conducted in 4,500 MSM and transgender women under the leadership of the HPTN is launching any day if it hasn't launched quite yet. There's also a companion study that will be done in women.
How long is all this going to take? Obviously, Truvada has been approved for treatment. Those studies started in 2011, [00:22:30] were completed in 2007. They completed in 2011 and FDA approval happened in 2012. That was a drug that was already approved for treatment. Dapivirine ring and cabotegravir are new chemical entities for the Ring and ASPIRE studies. We're guessing FDA, the dossier is going to be submitted in April next year. FDA approval or EMA could happen sometime in 2018. I think what we have to remember for some of the new chemical entities is probably in the 2023 to 2024 range before those products [00:23:00] will be available.
Forecasting ahead, when we look at where we are today and where we're going to be, possible ring licensure 2018-2019, we should see the results of the injectable cabotegravir studies and 2021 maybe licensure out there in 2024. You heard Daria Hazuda talk about some of the really exciting work being done with implantable ARVs, and I think, I hope those are out there on the horizon for us as well. [00:23:30]
But I think the HIV prevention field and the use of small molecules for prevention is a really exciting space right now. All the lessons that you've learned and a lot of drug development expertise is now really fitting all of these molecules into different formulations which could be used. I've just listed on this slide all the different drugs that are being put in these different formulations. It's a really exciting time. There have been great, [00:24:00] I really think breathtaking progress over the past decade with broad implementation of PrEP and the success of new sustained delivery and very safe formulation. There's a lot of enthusiasm for the next generation formulations of pre-exposure prophylaxis but I think clinical trials are going to be incredibly complicated because already we're seeing placebo-controlled trials are no longer possible. Thanks so much for the honor of being here today.
Harriet Robinson (Moderator): Questions? I have one over there.
Participant 1: Thank you, I mean, this is beautiful work. I just wanted to find out did you by any means try to find out whether there are any behavioral changes because of the confident that they have in the ring or the [00:25:00] tablets in terms of their sexual behavior?
Sharon: I'm not sure I quite understood your question. We have a whole team of behavioral scientists and they could talk to you for three weeks about all that behavior work that's been done both with oral PrEP and with the rings, but what we find is that people become when something goes from a placebo-controlled trial to an open-label format people, become much more confident in the product and that what they have many of the concerns or reasons they didn't use [00:25:30] products were because of the uncertainty of its efficacy because we tell them every month we're not sure if it works in a placebo-controlled trial and because of concerns about safety. Once you go to the open-label extension types of studies, then people have many fewer concerns. So, yes.
Jim Curran: Sharon, thanks for the terrific and very thorough and review of everything that's going on. I agree with you it's been remarkable progress. [00:26:00] For men who have sex with men and for women and men in some African countries and others, there's really nothing more important than HIV prevention. However, for many women in many parts of the world including the United States, concerns about STDs like chlamydia and gonorrhea, and concerns about unintended pregnancy, are arguably more important or equally important. Are there any combination [00:26:30] prevention trials going on? Because I get very concerned about ignoring gonorrhea and chlamydia in women in the US, for example.
Sharon: Well, you and I sing the same song about STIs. We sure are. Actually, when you talk to young women they say to us, "Why should I have three products, one for STIs, one for on my HIV, and something else for family planning? Why can't you?" This is what one of the young women told me a week and a half ago when I was there, "You scientists [00:27:00] need to go back to your books. You need to make these pills smaller and you need to find one product that can take care of all my problems because I'm worried about STIs and pregnancy too." I think we have to listen to that because they do worry.
Tenofovir in a ring form can reduce HSV at least by 50%. There is some work moving forward trying to develop multi-purpose technologies or actually utilizing prophylactic strategies [00:27:30] for STIs but I would say that's early on. But I agree with you where we need to be are products that can be used to actually provide much broader protection because the STIs are fueling the epidemic too.
Participant 2: I had the great privilege of working with Dr. Paul Janssen to actually help create dapivirine and rilpivirine and sadly he passed away in 2003, but this vaginal ring approach was one of the things [00:28:00]that he was most excited about. Given the incredibly minuscule delivery amount. I remember the original formulation was supposed to have 100 milligrams. What are the prospects for actually increasing the dose, because I'm sure that that has something to do with the efficacy aside from compliance issues?
Sharon: Right, there's a new next-gen ring, next-generation ring. It's a ring that's three months, has 200 milligrams, and will give [00:28:30] you higher levels. This was the first shot. I think it proves the concept and I think the next-gen ring would in fact have higher concentrations.
Participant 2: Thank you so much for that wonderful talk.
Emilio Emini: Sharon, I just want to put in a note of caution here because the challenges here are still substantial. I mean, the biggest challenge, of course, is adherence. Whether it'll be the ring, whether it'll be oral pill that would need to take particularly these populations of southern and eastern Africa of young women. I mean, [00:29:00] your data shows a very nicely on the ring. Even with that, adherence is a significant issue.
Also, I think we're going to have a regulatory issue that we need to be careful of here. That is that neither of those two studies, the Ring study nor the ASPIRE study, which were the phase III studies, met their pre-specified endpoints. From a regulatory perspective that is, by definition, an issue, and the analyses that you showed up, retrospective analyses so you have that issues associated with that one as well. Even though there's a lot of promise here [00:29:30] there's still a really, really long way to go. I think in the end, my favorite and I think a lot of people's favorite and your favorite as well you mentioned it would be the passively administered long-acting agents, if we ever get to the point of actually being able to do that.
With respect to Truvada and the ability to use Truvada, I'm funding right now a very large study in Kenya in populations that are particularly at high risk, to see will this is [00:30:00] in fact work. It's 25,000 people. Will they take it? Will they take it consistently? Can it be gotten out there? Will the cost effectiveness make sense for people who are paying for it and what have you? We will learn over the next three to four years, in a broader population, how well Truvada will work as pre-exposure prophylaxis. For the ring, I'm hoping for the best, but the regulatory pathway is going to be hard. We'll see where that winds up.
Sharon: Yes, we remind you that the iPrEx study also [00:30:30] failed to heed its pre-specified end points. Yes, I put a giant question mark there because we don't know. I very much appreciate your question. I think we don't know until we know. The bottom line is, I think, this we'll find out more if in fact people do take this up, and we'll be much more convinced if we see better efficacy with better uptake in some of the studies, just as we did with [00:31:00] iPrEx. After iPrEx, with IPERGAY and PROUD. I think that will make a huge difference.
Emilio: That's what really pushed the agency.
Sharon: That is what pushed the agency. Right.
Emilio: You need to have those follow-up studies. If that works for the ring, that's fine, but we have to wait and see how they turn out.
Sharon: Right, absolutely.
Emilio: It'll take a while.
Glenda Gray: Sharon, I wanted to ask you about the efficacy of the ring in young girls. The NEJM (New England Journal of Medicine) article where you shared the [unintelligible 00:31:21] the efficacy in the young girls—It showed actually a [00:31:30] reversal of the active arm versus the placebo in comparison to the older woman. You've attributed that to lack of adherence. Could it be anything else? If it was lack of adherence, wouldn't the slabs have been on top of each other? Do you think that there was a difference, and that you've seen anything that could be of concern in the younger woman?
Sharon: Yes. Thanks so much, Glenda. Yes, you're correct that in the intent-to-treat analysis I [00:32:00] went over very quickly. In young women who used it, the ring worked very well. Even in the initial intent-to-treat analysis, it worked great in 18-year-olds and not 19 and 20-year-olds. It's the vagaries of small numbers when you do sub-analyses. Not surprisingly, within NIH support, doing a lot of in-depth look at safety and looking at tight junctions, microbiota changes in the younger women to make sure that there wasn't something else there that we needed to pay attention to. [00:32:30]
Participant 3: Hi. Thanks for this talk. I was wondering if women's reported adherence matches the adherence data that you got from the rings? And if not, are there any other explanations for how pharmacokinetics work with absorption in different women's bodies that could account for these differences, or at least, for some of the differences? Have you actually looked at the gap between [00:33:00] reported adherence and measured adherence to see who it is who falls in that gap who's maybe not reporting what they did?
Sharon: Sure. Non-adherence or self-reported adherence correlates extraordinarily poorly to oral PrEP adherence for sure. We saw much better concordance, and actually young women reported to us they were taking the ring out much more often. They took it out for a lot of reasons. [00:33:30] Actually, once you did the analysis in the younger women and accounted for the women saying they took it out, actually the age effects went away. All I'm trying to say is there's a very different relationship of women with this product as compared to oral products, that I think, it's not that they were entirely truthful, but we didn't see the broad scale misreporting as much as we did with oral PrEP.
Harriet: I think it's time for us to [00:34:00] move on.
Sharon: Thank you.
Harriet: It's a very interesting talk. Thank you for coming to Cold Spring Harbor.
[00:34:09] [END OF AUDIO]
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- 2.1 Paul Volberding — The First Patients
- 2.2 James Curran — Deciphering the Epidemiology of AIDS
- 3.5 Daria Hazuda: Discovery and Development of Integrase Inhibitors
- 6.5 Emilio Emini — Issues in HIV Vaccine Development: Will the Future be any Easier than the Past?
- 6.6 Robert Redfield — The PEPFAR Program to Treat HIV in Africa
- 6.7 Salim Abdool-Karim — Stopping the Spread of HIV in Developing Countries
- 8.1 John Mellors — MACS and Beyond: Epidemiology, Viremia and Pathogenesis
- adherence, patient compliance
- Africa, sub-Saharan Africa
- Black Death, bubonic plague, Yersinia pestis
- blood — banks, donors, plasma, screening, transfusions, clotting factors (factor VIII), PBMCs
- CAPRISA 004 study (2007–2010)
- Celum, Connie L.
- Clemetson, David B. A.
- clinical trials (phases of clinical research)
- Cold Spring Harbor Laboratory (CSHL)
- Conference on Retroviruses and Opportunistic Infections (CROI)
- control — experimental control, control group, blinded experiment
- dapivirine (DPV)
- drug safety
- education and early career
- Europe, European Union
- European Medicines Agency (EMA)
- FDA (US Food and Drug Administration)
- Fem-PrEP study (2009–2011)
- Fred Hutchinson Cancer Research Center
- FTC (emtricitabine, Emtriva, Coviracil)
- HIV Prevention Trials Network (HPTN)
- Holmes, King K.
- HPTN Study 052 (2005–2015)
- implants, drug delivery implants, implantable antiretroviral therapy
- integrase inhibitors
- International Partnership for Microbicides
- IPERGAY Trial (2012–2015)
- iPrEx (Iniciativa Profilaxis Pre-Exposición) study, 2007–2011
- Janssen Pharmaceuticals
- Kreiss, Joan K.
- maraviroc (Selzentry, Celsentri)
- microbiota, microbiome
- Mount Vernon, Washington
- National Institutes of Health (NIH)
- New England Journal of Medicine (NEJM)
- non-nucleoside reverse-transcriptase inhibitors (NNRTIs)
- North America
- pre-exposure prophylaxis (PrEP)
- PROUD study (2012–2015)
- public health
- Rakai Health Sciences Program (RHSP)
- rilpivirine (Edurant)
- Sande, Merle (1939–2007)
- Session 6: Immunology and Prevention
- Session 7: Prospects for an HIV Vaccine
- sex workers
- sex, sexually transmitted infection (STI)
- South Africa
- South America
- tenofovir (TDF, Viread)
- toxoplasmosis, toxoplasma gonii
- treatment-as-prevention (TasP)
- vaginal ring
Found 3 search result(s) for Hillier.
... Dan Barouch (BIDMC/Ragon Institute of MGH, MIT and Harvard) 6.1 Sharon Hillier — Development and Application of Preexposure Prophylaxis (PrEP) https://libwiki.cshl.edu/confluence/pages/viewpage.action?pageId=12943553&src=contextnavpagetreemode 6.2 Dennis Burton — How ...
Mar 18, 2021
... have time for one more question. One short question in the back. Sharon Hillier: This one is short. I'm Sharon Hillier from the University of Pittsburgh, I work in HIV prevention and thank you so ...
Mar 06, 2021
... study (2007–2010), and there were many others working exactly in this area. Sharon Hillier, 00:20:30 there were people working in the field in FHI (Family Health ...
Mar 06, 2021
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