Clinical Education Initiative Support@ceitraining.org PRE-EXPOSURE PROPHYLAXIS Speaker: Antonia Urbina, MD 9/6/2017
Pre-Exposure Prophylaxis [video transcript] 1 00:00:07,480 --> 00:00:09,139 I mean we're like really scaling up PrEP down here at Mt. Sinai across all of our sites. So it's definitely an important intervention. 00:00:18 So I'm going to speak on that. 00:00:22 So these are my disclosures. 00:00:26 And these are the objectives so I am going to weave in the New York state and CDC guidelines for PrEP, describe candidacy selection of candidates for PrEP, and the management of the patients on PrEP. 00:00:40 So this was a very interesting site. So this is from the CDC the national HIV surveillance system data. And it looked at trends in HIV infection among men who have sex with men from 2008 to 2014. So the good news is that we've seen a slight decrease in new HIV diagnoses among men who have sex with men from the years 2008 to 2014. However we've seen significant increases in Hispanic Latinos with new infections in seven states and in African-American men in eight states and in those between the ages of 13 and 24 and 25 to 34 in 16 to 18 states. We've seen significant decreases However in whites in 14 states and in older MSM and 23 and seven states, respectively. So really trends at the national level obscure these important kind of my group geographic variations in HIV incidence. But I just wanted to circle in New York so New York's doing great in terms of really significant decreases in all MSM in black and white. So you'll see that green means decrease in incidence but where we're seeing increases in all MSM is in the south. Right. Look Alabama, Arkansas, Arizona is in the southwest but Louisiana, South Carolina, and Texas. So again, these are the regional variances in HIV incidence. But again, overall the trend is down however increases in Hispanic Black and those younger aged MSM. 00:02:33 All right. So the opposites attract study looked at HIV transmission in MSM serodiscordant or magnetic couples, one's positive the other negatives, in Australia, Thailand and Brazil. So this was 591 couple years of follow up in about 360 couples. Over 80 percent were on antiretrovirals. About 80 percent had an undetectable viral load. Close to 60 percent reported anal sex with outside partners. And there was about a 12 percent incidents of our actual prevalence of STI's. And what they found is with all these couple years of follow-up, and over 7000 acts of condom less anal sex, that there was no linked transmissions. So zero. And if you basically look at any so for any inserted condom less receptive. And then they also interesting look at dividing up viral loads those that were rarer than 200 even less than 1
200 and no linked transmission in this MSM cohort so this kind of supports the view that a person who has consistently undetectable HIV RNA levels, and is adherent to their medications has really a really negligible chance of transmitting to their sexual partner. So this adds to the increasing data showing that undetectable really does equal un-infectious 00:04:06 OK. So they also presented more data on the PROUD study. This is a long term follow up of PrEP use in a real world setting. So this study was actually first presented at Kroy last year, it's a multi-center study in the UK, 13 sexual health clinics and it was basically an open label study looking at HIV negative men who have sex with men who engage in condomless, anal intercourse they could have a history of hepatitis B. Co-infection and what they did in this study is that they had they had a first phase and in it phase. Is that my echo? [Rob Walsh] Someone needs to mute their line. Ok thanks. 00:04:58 [Dr. Urbina] Yeah. So this study to the quarter of patients so randomize them to either immediately start on on Truvada or to defer for 12 months. And the DSMB monitoring board basically had to interrupt the study because the immediate arm showed an 86 percent reduction in HIV acquisition. So now what they did is that those in that deferred arm were then allowed to start on Truvada because it showed efficacy and now at the resent IAS conference they show their data for this extension arm. 00:05:35 So what they found, and look at the deferred phase, there were four HIV infections in those that got Truvada immediately versus 21 in the deferred. So in this post-deferred where everybody got Truvada, you'll see that it was five and one new infection. So again really supporting that even three years after initiation. Just two years after initiation that PrEP was still efficacious. Now what we see here is that the rates of STI's in this extension phase remained high. So 30 percent rates of rectal gonorrhea about 30 percent rates of rectal chlamydia. We do see that the rates of syphilis did tick up in the extension phase. So we saw a sustained reduction in HIV with PrEP. And we saw high rates of STI which really reflects the ongoing risk and need for patients on PrEP 00:06:38 OK. And then they also provided an update for the IPERGAY substudy. And this is on demand PrEP amongst high risk MSM and they really wanted to look at infrequent sexual intercourse amongst their cohorts to see if this On-Demand PrEP was still efficacious. So just to review, this was a double blind open label study both in France and Canada. Participants had to be HIV negative with their test at least within one month. High risk MSM, and they define it as having at least two partners within six months. Also condom-less sex, normal kidney function, normal liver function. No coexisting HPV or HCV. So basically the strategy for this one was that patients either receive active drug or placebo and it's two tablets of Truvada two to 24 hours before sexual exposure than one tablet 24 hours after. And then one 48 hour hours after so four around the time of the exposure. But what happened is that the majority of these participants had so much exposure that they were averaging about four tablets week which is kind 2
of the dosing that you need to to obtain protective levels. So what they did is that they look at a set cohort of these patients who took less than 15 tablets per month so have less frequent exposures and they wanted to provide outcomes of that. 00:08:17 And what they show here. So there was approximately 269 participants that reported less than 15 PrEP pills per month. Their medium number of pills per month were 9.5 medium number of sexual intercourse per month was five. And what they found is no new HIV infections amongst the PrEP arm that had fewer than 15 pills on PrEP and there were six new infections in the placebo arm. So that's an efficacy of 100 percent in patients that adhere to this On-Demand PrEP with less frequent encounters. So you know it really supports a little bit more of this view that this On-Demand PrEP may be effective in MSM with less frequent sexual encounters. However, both the CDC and the New York state still do not recommend On-Demand dosing for PrEP. But, I think this is a conversation that I would have for my patients that say hey I want to minimize exposure to Truvada. Our is there any data that may support shorter courses of PrEP. 00:09:24 So I think this was very compelling as well. All right so they also had a substudy On-Demand amongst high-risk MSM who participate in Chemsex and they defined Chemsex on the bottom left here is "use of psychoactive substances during sex". So basically drugs like gamma hydroxybutyrate, methamphetamine, methedrone is another one that they use and this was in a substudy in this. They also included injection drug use especially methamphetamine. So this was a substudy of the Open Label section period. They saw no difference in social demographic characteristics between chemsexers and non-chemsexers. Chemsexers had more vulnerable psychological profiles, more anxiolytic consumption, and higher sensation seeking scores. The chemsex practice was associated with more PrEP use which was good, more casual multiple partners and more high risk, hard core practices like fisting. And PrEP what they found is a suitable tool to reduce HIV transmission in chemsexers. It really provides us an opportunity to provide prevention interventions, especially PrEP, to participants that do engage in chemsex. So this is the highest of the highest risk. What we do know is that there's no direct drug drug interactions and Truvada. So just looking at the right chemsex and PrEP use, so some of the differences between those that reported chemsex versus no chemsex. So again, there was higher anxiolytic consumption, probably with their methamphetamine crash. There was higher sensation seeking scores and those that there was higher injection drug use with chemsex versus non-chemsex. There was more sexual encounters and those sexual encounters tended to be less with their main partners more with casual partners and more with multiple partners. But again higher PrEP use which I think is important so that in this cohort of patients you know definitely PrEP can still be a viable actual strategy for HIV prevention. 00:11:48 All right. So this is looking at the national electronic prescription database for new PrEP starts in the U.S. I think more recent data shows about 130,000 U.S. persons are on PrEP. So you'll see that, since its 3
inception, the growth has been somewhat exponential with about seven times increase since the third quarter of 2012. The majority of starts have been male, 85 percent, with female, 15 percent. 00:12:20 Now this is where I think it's disappointing. Let's look at PrEP utilization in the U.S. on the left PrEP use 2016 basically kind of reflects the U.S. demographics but so 73 percent of PrEP utilizers are white, 10 percent are black, 13 percent are Hispanic, and 4 percent are Asian. Look at the graph on the right. Latest data from CDC looking at new HIV infections by race 44 percent black, 24 percent Hispanic, 26 percent white, and 2 percent Asian. I think that graph is very illustrative. That we're not really meeting our target populations, at all. And why are we not? 00:13:19 So this was a study that was done by Ken Mayer out of Fenway and he did a survey study. So he sent out a survey for MSM from the U.S. He posted these two surveys on two very popular sexual networking sites and what he found is that condomless anal sex occurred at least twice in the past that occurred past in the three months at least 75 percent of the respondents acknowledged condomless sex at least twice in the past three months. The majority of them had not used PrEP and 22 percent were unaware of PrEP the major barriers to PrEP uptake. And let's look at the right first so the reasons for not using PrEP amongst these informed non-users. So these were ones that knew about PrEP but were not on PrEP close to 3000. So their major concerns were costs, 40 percent. Potential side effects, 31 percent. Potential effects on insurance, 20 percent. Their medical providers reaction if I asked for it, so concerns about that, 18 percent, 30 percent do not know where to access PrEP so again, access issue. And another 19 percent do not feel that they were at risk. So if we break it down a little bit the major barriers to PrEP uptake were divided up into structural factors. So cost, access, insurance, anticipated side effects, and low perceived risk were the major categories while the vast majority of this cohort was not on PrEP. So the most common PrEp uptake barriers by subgroups, so older MSM were more concerned about the anticipated side effects, potentially. And then for access concerns they were much more common amongst black MSM, less educated MSM, and MSM born outside the US undocumented, which kind of makes sense. And it results really underscores the need to educate at risk MSM and address these access concerns about disproportionately affected groups. But again a huge disparity where we need PrEP to be really scaled up we're not really penetrating into those sectors. 00:15:58 All right. And then the last slide here is HPTN 077 so this is the future for not just prevention but also treatment. So this is probably the first one that's going to come to market is the long acting injectable cabotegravir. So the study is looking at the drug concentrations in low risk HIV uninfected women and men and they have two dosing arms that they were looking at so 600 milligrams every two months or 800 milligrams every three months. So this is an ongoing randomized three to one phase 2a doubleblind placebo controlled trial in Brazil, South Africa, Malawi, and the U.S. And they're looking at intramuscular cabotegravir, 600 every two months, 800 hundred every three months. This is the break out for the demographics so the median age 30, 34 percent male, 27 percent white, 41 percent black, 24 percent Hispanic. So great spread on the demographics and on gender. Both cabotegravir doses were 4
well tolerated. What you want is for the trough, so when those lines go down, you want for the troughs to be above that four times the IC 50. So it looks like the 600 milligrams a week arm had better pharmacokinetics. But both were well-tolerated. They just reported some mild injection site reactions but they're going to be moving forward with this 600 milligram q8 weeks after a four week loading dose with the oral cabotegravir and it looks like that's gonna meet the pharmacokinetic targets. And now they're in phase 3 studies so this will be coming soon as effective kind of new formulation for PrEP. 00:18:00 And there special thanks to Ian Frank, Chris Ferraris, Simply Speaking. [end] 5