BIDC Resources for Healthcare Providers

Healthcare Providers and Public Health Partners Call Presentation, March 14, 2024

Transcript of video:

all right uh good afternoon everybody uh why don't we go ahead and get started it's just a minute after the hour um let

me first start by welcoming all of you again to our monthly uh Public Health webinar uh today's topic as you can see

on the screen is going to cover um garia chedia and doxy cyclin postexposure

prophylaxis um I am recording this webinar and it will be posted online afterwards similar to the syphilis uh

webinar that we conducted a few months ago um and we're going to start off here with uh Dr altamare from darmouth

Hitchcock Medical Center uh presenting on the national epidemiology of garia

and chlamydia and then talking um I'm giving a a brief clinical didactic on um

testing and treatment recommendations for chyia and ganara and then I will take over and talk about New Hampshire

specific epidemiology very briefly and then uh talk about doxy cyclin post

exposure um prophylaxis um just as a reminder uh the chat function is

reserved for us posting links and information to all of you uh if you have

a question please use the Q&A box um we will not be taking hand raises or verbal

questions so if you have a question or comment please use the Q&A box which can be found in the zoom toolbar um also as

a reminder these slides will be posted online on our healthcare provider website which hopefully all of you are

familiar with um would also encourage you all to um go back and watch the earlier companion webinar to this one

that uh was recorded and posted online about syphilis and congenital syphilis

that is also um on this website uh so with that why don't I hand things over

to Dr altamare and she will get us started here by talking about the national epidemiology of garia and chyia

and then be uh briefly talk about testing and treatment recommendations before I take back over Midway through

um so Antonia go ahead thank you Dr Chan and uh thank you all for signing on another one of my favorite topics garia

and chlamydia um so this kind of first um intro slide kind of gives you high

level statistics of how many people in the US have an STI um and so as of 2018

this data was one in five and of uh most significance is about almost half of the

new STI were among youth aged 15 to 24 next slide

please so just to set the stage the the newest data we have is actually from the year 2022 and as you can see um there

were 1.6 million cases of chyia and around 600,000 cases of Gonorrhea these

are new newly diagnosed cases and so for chlamydia it seemed like it was a slight

decrease compared to 2018 data um but garia has been on the rise and we've

touched on in Prior lecture syphilis so I'm going to skip over that statistic today next

slide as you know if left untreated STI can cause um an increased risk of giving

or getting HIV there are also long-term pelvic or abdominal um consequences such

as pain and infertility um so the real key is to talk about it test for it and

treat it next slide so just to give you kind of a l Escape of what STI are most prevalent

and where new infections are happening and a reminder that prevalence is the estimated number of

infections um that are that people are living with at any given time and incidence is really the estimate of new

infectious infections diagnosed or undiagnosed and you can see here um far

above many others HPV Remains the most common sexually transmitted infection followed by herpes

hsv2 um and tronus camia make up kind of the top four in fact all of these make

up around 98% of all prevalent STI and 93% of all incident STI so although we

talk a lot about syphilis and gonorrhea they are overall um less numerous than

than chlamydia and some of the other infections next

slide so just wanted to kind of give you what um these infections have been looking like over time so we're going

back really far in some of these graphs um for chyia the upper left you can see

this graphic is from the year 1984 until around 2020 and the overall

General trajectory looks a little bit like the stock market so overall has been going up um where the arrow is

that's where they um the US CDC had decided to make this a national

identifiable condition um so you can see that it was plateauing a little bit before then but once reporting had

kicked up you can see that it's been nothing but up of note there's um a few hiccups or bends in a lot of slides

between the years you know 2020 and 2022 and that actually has to do all with the

covid pandemic where um testing had actually dropped off and so we saw less

cases but that doesn't mean there were less cases um it was more of a testing um void uh so if you look over at the

top right garia that graph definitely looks different and the um year span is

really 1941 so 40 years prior to where the chyia slide starts and you can see

that there was a nice dip in in around the 60s which actually we could probably

a tribute to penicillin um back in the day that's no longer the recommended treatment for Gonorrhea but its cousin

is and then you can see how there was a spike in the 880s came back down in the early 2000s and now we're on our way

back up um just looking at some of the more specific demographics when it comes to Asian gender they are different between

chlamydia and ganaria um you can see for chlamydia the bottom left box that there

are more females um infected with chyia and if looking at goria there are more

males but the age distribution is very similar and tends to affect again that youth AED

population next Slide the other thing to point out is

for both chyia and ganaria this graphic looks exactly the same and that is the

fact that um ethnic minorities are dis disproportionately affected by these

infections so you can see on the left um white and purple that's the percent of

the population that white people make up and what percentage of infections are

made up of white people and similarly for black being the most starking kind of color that goes pretty much from

pretty low down on this graphic at 12% of the population however black africanamerican make up about 28% of all

infections next slide so the disparities so as

previously stated 50% of reported cases of STI were among adolescence and young

adults age 15 to 24 in 2022 and 31% of all cases of camag goner and syphilis

combined were among non-h Hispanic black or African-American persons although like just stated they make up the

minority of the US population and men who have sex with men are disproportionally impacted by STDs

including gonorrhea and syphilis in fact 36% of men who have sex with men who

were diagnosed with syphilis also had concurrent HIV and so the quote from the CDC is that these disparities are

unlikely explained by differences in sexual behavior and rather reflect differential access to Quality Sexual

Health Care as well as differences sexual Network characteristics next

slide I also wanted to note that not only are the absolute numbers of infections going up but we're having an

increasing problem with antibiotic resistance um so this graphic just shows

different types of antibiotic specifically used for neria gara um and

the percent um that have increasing mic's or that minimum inhibitory

concentrations which it's eventally essentially makes them less effective against the bug so half of all

infections in 2022 were estimated to be resistant or have some um elevated level

of minimum inhibitory concentrations to at least one antibiotic but almost all

the circulating strains in the US remain susceptible to sep triaxone which is the primary recommended treatment for

uncomplicated gonorrhea next slide in fact some of you may have seen this Han that came out now

a little over a year ago January 2023 where there have absolutely been reported cases of resistance or reduced

susceptible um gonorrhea in Massachusetts and so the Han really

reiterated um the importance of screening treating um and if a suspected

treatment failure to really obtain a culture which we'll talk about when we talk about Diagnostics next

slide so we can't really talk about STI without talking about sex and I may have mentioned this before but a sexual

history taking should be taken as part of routine health care and I know when I was in med school and in training this

was not a huge part of my training talking about sex is uncomfortable for a lot of reasons um but it allows you to

really provide high quality Patient Care by appropriately assessing and screening individuals for a broad range of sexual

health concerns and an opportunity to educate patients normalize those behaviors and discuss harm reduction

next Slide the CDC puts out this wonderful um booklet it's um the size of

a pocket so it can easily fit in your pocket um and it follows the five PS of sexual history taking so these are kind

of the five categories you should be addressing um when speaking to patients who are your partners what do you do

with them do you use any protection from STI what are your past history of STI and what are your pregnancy intentions

um they actually have wonderful quotes within in the booklet on how to actually frame the question um and you know be

able to risk assess that patient this is important because when it comes to screening it's really important to

screen all sites of exposure and that might not just be a urine specimen next

slide so what are the recommendations so these are the um latest uspstf screening

recommendations for garia and clamydia for all sexually active women 24 years

or younger or 25 years and older with increased risk which you'll see below it's recommended that they be screened

for Gara and chlamydia so what does it mean to have increased risk it means a

previous or coexisting STI a new or more than one sex partner a sex partner

having sex with other partners at the same time a sex partner with an STI inconsistent condom use when not in a

mutually monogamous relationship a history of exchanging sex for money or drugs or a history of

incarceration on the other hand the recommendation for men um is that the

current evidence is insufficient to assess the balance of benefits and harms of screening routinely for clidia or

ganara in men I do want to point out on the next slide please that the CDC as of

2021 had updated their screening guidelines and not only do they List It by disease but you can List It by

population so I wanted to bring your attention to um the category of men in

particular men who have sex with men next slide there actually are very specific

recommendations for screening menu of sex with men and it's recommended that this be done for both clim and ganaria

at least annually for any sexually active men who have sex with men at sites of contact so that would mean

urethra rectum um and in the case of goria the fairings and if they remain at

increased risk it's recommended to do it more frequently perhaps as frequent as every 3 to six months so you can see how

this differs slightly from the blanket statement from the uspstf where they um

you know it's a it's a grade I recommendation because there's not particularly strong evidence to screen

all men but if you get down to kind of risk categories um you can see that

there may be indication to screen certain men next slide so how do we screen the gold

standard for chlamidia and ganaria is a nucleic amplification test Um this can be done on various

specimen types vaginal or cervical swabs are sufficient for um anyone with a

vagina um or a first void urine which tends to be a little more difficult because by the time you're seeing a

patient in your schedule at 2 o'clock in the afternoon they've certainly already voided um patients can collect their own

specimens and a vaginal swab collection is equivalent in sensitivity and specificity to those collect Ed by a

clinician um the same goes for urine samples being comparable to a cervical

or urethal urethal swab as long as it's um a first uh a first day collect um you

can also use these swabs for the Oro fairings the rectum um and in babies we

often use it for the conjuntiva the key here however is to test all sites of

exposure next Slide the reason being there's now two well documented studies

looking at positivity rates and incidents of STI in various populations

and in this first one you can see that extrog genital goria and chyia were common among MSM men who have sex with

men attending this particular STI clinic and More than 70% of extrog genital Gara

infections and 85% of extrog genital chlamydia infections were associated with negative urethal tests at the same

visit and hence would not have detected up to in this case 85% of infections if

only the urine or the urethra were screened this same thing is now been proven and seen in a separate study done

um in in a cohort of patients infected with HIV at a HIV Clinic um who had

multiple sight testing and in this cohort found that 96% were positive only at an extrog

genital site we have have pretty much the same experience within our HIV um

population and in our clinics whereas if we do multi-site testing almost always

the the positive tests are coming from anywhere other than the urine or

urethra so if you can't remember the words remember this image and I apologize if I've ruined ice cream

Sundays for the rest of your life but remember the triple dip you're going to test for rectal urine and Fingal Gara

and CLA with the caveat that there's actually not enough evidence to screen

for chlamidia in the ferx because the clinical significance is not well known

so it's not actually a routine recommendation to screen however if it's found because you're using the same swab

and both tests are run on the same swab then you should treat because you certainly can transmit if there's um

chyia in the fairings and then the chocolate sauce and Cherry are the HIV syphilis and in the case of rectal

receptive sex Hepatitis C serology so all of these are potential infections

that can be acquired through sexual contct the the top HIV syphilis and Heep

C are blood tests and all the others have to be done through either swabbing or urine collection using um very

specific swabs so the next slide will show you exactly what that means um so

the swab that you should have on hand is is and this is just one Manu facturer

it's a it's a collection swab for endocervical and it's it's labeled in male urethal specimens but again it can

be used and and is FDA approved for use at other sites um how do you do it is

the most common question I get and it is quite simple if you've ever done strep tests swabbing the oral fairings is very

similar you want to you want to swab both tonsils um pillars the back of the

oral fairings and all the way around so you can make one big sweep like in in an upside down U fashion and you've got

your specimen you put that right into the tube and you label that with

obviously a patient label and but label it throat because you're going to be sending down several specimens and you

do need to know which specimen is positive if there is one because treatment guidelines May differ for

rectal swabbing just as easy you take out that blue swab and you stick it

about an inch into the rectum and twirl it around for about 10 seconds both of these swabs can be done by the patient

in fact most patients opt to do the rectal swab themselves most have a little more difficulty difficulty

self-collecting the oral fial swab and finally the last picture is a picture of

a vaginal swab um which again most patients opt to self-collect same maneuver about an inch or two into the

vagina spin it around for about 10 seconds put it into a separate bile so it should be separate swab separate

vials for all specimen site collections next slide

so what are the treatments so you do all this swabbing and you get test results back 2021 guidelines have changed quite

significantly from the prior iteration for STI treatment and probably the biggest change was in the treatment of

chlamydia which AI used to be the main state of treatment has now been moved to the alternative because doxy cycl has

proven to be much more effective especially when treating um rectal mucosa for chlamydia so the newest

guideline and recommendation for treatment of chlamydia is doxycyclin 100 milligrams orally twice a day for seven

days so you might ask gosh the adherence to this is going to be a lot less than the athra 1 gr which used to be a single

dose we haven't found that to be the case most people do just fine taking it

but know that if you worry about adherence you can use the aiyin they're

just maybe lesser efficacy particularly if you're trying to treat um rectal

mucosa um advice to the patients should be that they should abstain from sexual intercourse for the first seven days of

treatment um because that's about how long it takes to be effective otherwise they could potentially still be at risk

of transmitting infection and partners have to be notified and we often leave

this up to the patient um uh and partners means anyone that they've had contact with in the last 60 days of

diagnosis should be tested and treated and anyone who receives a diagnosis of

chlamydia should certainly be tested for HIV gonor and syphilis which you're doing probably chamian gonor at the same

time but don't forget upfront if you're testing for STI it means you should be testing for all of

them great so a word of caution on a particular strain of chyia which we've

definitely seen clinically here and that is a syndrome known as lymphogranuloma

Venum which is caused by a very specific Cobar of chlamidia trus it's L1 through

three um and it it causes a very different syndrome so what I haven't mentioned so far is that most cases of

chlamydia and even gonorrhea are asymptomatic so the intent of screening

is to pick up an asymptomatic infection and screen it certainly if someone comes in with symptoms you absolutely should

be testing for uh and treating any positive test that comes back but in the

case of this particular bug and syndrome this is very symptomatic and L

symptomatic it often causes tender unilateral ininal lymphadenopathy it could cause genital ulcers but the

syndrome we see most is that of proctocolitis which for all intents and

purposes mimics and looks exactly like IBD it has um significant colonic

inflammation diarrhea maybe constipation blood mucus colonic fistulas and

strictures that could develop and this isn't over a prolonged period of time this inflammation happens very quickly

but will persist without treatment and in fact I've had patients who've been seen by um various GI coloral surgeons

and they you know just assumed it was all new diagnosis of IBD but the

diagnosis is getting a rectal swab for GC chlamydia or in this case very

specifically chlamydia the same chyia you're testing for um in the other slides that I mentioned so a simple swab

of the rectum will give you the answer if it comes back for chlamidia trus and

they have this syndrome then essentially you can say they have lymphogranuloma Venum and need treatment for that which

is as you can see different than the 7-Day course you would give for asymptomatic rectal chamia so this is a

21-day course of doxy cyclin and symptoms should completely resolve there

is no commercially available test to actually tell you the zerar of the

chlamydia so this diagnosis and treatment is really based on a combination of the clinical syndrome and

a positive rectal uh swab next slide great so moving quickly

on to gonorrhea um there were also some updates to the treatment of gonorrhea

and that mainly had to do with the dose of seph triaxone so sep triaxone has been the um main stay of treatment for

quite some time now because as you remember ciprofloxacin athro other antibiotics that used to be used are now

quite resistant um the change here to overcome some of the rising mic's is a higher dose and to

note that it's it's a one gram dose for anyone who's over 150 kilos so really

pay attention to the weight of the person in the dose needed to treat um

ganaria uh the treatment is the same regardless of the site of infection

however there's one difference and that is if you're treating oral Fingal gonorrhea a test of cure is recommended

at 7 to 14 days because the sep triaxone tends to be a little less effective in

penetrating the Oro fial tissue than it is the other sites so we are on the side of retesting around 14 days because you

are testing again with a nucleic amplification test and if you test much earlier you may pick up on um non-viable

organism and it could be a false positive what you're really looking for is failure of treatment in this case um

and if symptoms if the person's actually symptomatic in any of these sites and you're treating for gonorrhea and

symptoms persist despite treatment then you really need to repeat not only a nucleic amplification but send a

specimen for culture because this will be the only way to get antimicrobial susceptibility testing and with the rise

in in the number of resistant isolates um this is this now should be the new Norm um if you have persistent symptoms

in the setting of symptomatic infection so there are alternative

regimens but they're not great so you can see here um if someone has a true sephos borin allergy then you're looking

at gentamycin and ethy um so it's not easy and I would

make sure for all those I'm putting air quotes around this word penicillin allergic patients truly have allergies

and try to flush that out before um uh deciding that you're not going to give them first line

therapy next slide great so followup test of cure is is pretty much not

advised for non- pregant persons but what is recommended is repeat testing

for anyone who's had a positive test um at 3 months after treatment and the reason there is not because we're

looking for failure um of treatment but you're actually looking for reinfection because the reinfection rate is really

high especially if Partners don't get treatment at the same time the only caveat to that are pregnant women they

always fall in a category of themselves given the risk to baby and so in particular when it comes to cidial

infections it is recommend that they actually have a test of cure at 3 to four weeks after

treatment next slide great so here we are at the end um if you take away

nothing else STI are on the rise a detailed sexual history is really important testing all sites of exposure

are the most important remember your triple dip and the swab you need to use and treat per the updated CDC guidelines

um the link to the guidelines are on this slide and were referenced in in the previous slides and you can go to the

next next side um the other you know kind of like little logo or slogan to

remember that hersa is actually pushing out is this ask test treat repeat it's as simple as that we need to ask test

treat and repeat and there's a little YouTube video there that you can watch too here are the references and know

that um the STI guidelines are available through an app super easy on your phone

when you click into it you can click on the disease entity it gives you all the treatment recommendations right there so if you don't happen to be you know

someplace where you're on a computer or they also have Wall um Graphics uh

pocket cards things like that um super important information to keep handy and

that's it thank you great thanks so much uh Dr alari for that excellent uh review

I am going to um take just about five seconds here to switch slides uh we

weren't able to combine them into one single deck my apologies for that that um and then I will pick up and take over

here and Antonia can you just confirm that you can see my slides now yep in

the correct presentation mode Perfect all right so thank you again Dr alari for that excellent clinical review I'm

going to talk very briefly about um the epidemiology of chlamydia and garia in New Hampshire although I'm going to move

fairly quickly through these slides because the patterns and the trends are very similar to what Dr Almar showed um

with the national Epi so this uh is a graph of the total number of cedia

infections diagnosed each year in New Hampshire going back to about 23 years

uh to the year 2000 so not quite as far back as some of the national graphs that uh Dr alar showed but you can see that

the trend here is um very similar where for a good decade plus we saw um gradual

and continual increase in the number of cidial infections each year that peaked

uh at just over 4,000 infections um before it has uh slowly down trended

when last year in 2023 we were almost at 2,800 chamia

infections um but the trend here is very similar to the National picture and if we stay on um chial infections this is a

graph looking at the total number of infections in New Hampshire by age and this is actually looking at the last

three years of data combined so 202 1 through 23 data is combined here and

again you can see that the majority of chlamydia infections are occurring um in older adolescents and people in their

20s um and 30s which is consistent also with the national picture and it's not surprising given that this is um partly

where the the screening recommendations uh Focus um and this contrasts with what I'll

show you in a few slides around ganaria um where there is a higher number of um infections in older age groups groups um

this is looking at the number of infections in New Hampshire by County again uh the 2021 to 23 data is combined

here uh and you can see that the the um burden of infection really is focused

around the Southern and uh Central parts of the states with uh Hillsboro County

having the highest number of chlamidia infections followed by Rockingham and then straford and Marram counties um

when we look at uh risk factors or reported sexual risk factors um you can

see that the vast majority we don't have information on so more than twoth thirds of uh people diagnosed with chlamydia uh

we don't know what their sexual risk factor is and then another quarter plus uh report um heterosexual uh contact the

the one of the main reasons for the large unknown category is simply the fact that we have um so many cidial

infections uh that many if not most of them don't get the uh full Public Health

investigation to determine risk factors and um sexual partners uh it has just

become um a a burden that is unable to be sustained um when doing Public Health

contact tracing hence we don't have a lot of information on on uh the people who are diagnosed with

chlamydia uh when we look at um ganara Trends this is a graph um looking at the

total number of Gonorrhea infections in New Hampshire East each year going back to 2000 the year 2000 um you can see

that this uh is very similar to the National trend for uh a good decade plus

we had a relatively stable um level of ganara infections at about 130 or so per

year um and then began to see a dramatic increase um around 2015 2016 where we

actually did um healthcare provider messaging at that time so some of you on this webinar may remember that messaging

back then about the dram increase in gonorrhea that had continued to go up and has not come down uh

2022 uh saw the most number of gonner infections at just over

670 uh last year U about 591 gonorrhea

infections were diagnosed in New Hampshire so we saw that dramatic increase back in 2015 2016 uh and the

numbers have remained High um since then in terms of age groups you can see that

you know still people their late teens 20s and 30s are largely impacted uh but we do see a shift to um older age groups

which is also consistent with um National ganaria trends that Dr Almar showed earlier uh in terms of uh the

geographic area impacted in New Hampshire this is um similar to the prior graph I showed for chyia looking

at the total number of goria infections now in New Hampshire by county and you can see similarly that um Hillsboro

County uh has had the most number of infections diagnosed followed by um

Rockingham and then straford and marrat counties and then similarly uh with

reported sexual risk factors there's about half of people diagnosed uh we don't have um or don't know the sexual

risk um about or on uh a little over uh a quarter report heter heterosexual

sexual contact almost a quarter report um uh men who have being uh men who have

sex with men um and so this is also not a uh surprising uh Trend

here so what are the strategies that we have to prevent the spread specifically of chlamydia in ganaria and I'm

specifically calling out climan ganara because with some other sexually transmitted infections for example HPV

we have a vaccine um Hepatitis B virus we have a vaccine um HIV you know there are

strategies like hi pre-exposure prophylaxis or prep that is utilized but with Clan Gario there is no

vaccine um and so a lot of our control methods Focus first on behavior

modification and risk reduction strategies so you know asking patients

uh or recommending patients reduce the number of sex partners have you know lower risk sexual encounters wear

condoms Etc um and that frequently is not um a successful or long-term

successful strategy and so then we look to healthcare providers and the healthcare system for secondary

prevention right early detection of infection through screening and testing um as highlighted by Dr almare you know

appropriate treatment retesting if appropriate um as I alluded to contact

tracing to identify exposed and susceptible persons often times uh is is

not successful either due to the burden of infections and reports coming in or

the simple fact that many people um do not want to or are unwilling uh to share

very personal information about um their sexual contacts uh and then there are

strategies that have been talked about previously around expedited partner therapy that's where providers um treat

Partners without necessarily having a clinic visit to assess them um but that is also difficult to implement from a u

clinical um perspective so there are a number of different strategies that uh

are used to prevent the spread of chlamy and ganara um and yet over the years we have continued to see uh rates of these

infections um overall continue to Rise um and so new strategies need to be

employed and investigated and that's where uh transitioning now to doxycyclin

postexposure prophylaxis uh comes in as an a potentially important tool uh for

controlling the spread of specifically bacter material STI this is a table from uh a from some

draft guidelines that CDC put out um a number of months ago

um this is coming but this is not yet formally released by the CDC and so you

may have heard about this in the media you may have seen um stories about this

you may have even seen um the draft guidelines eles when they were released a few months ago you can still find them

online but here is a highlevel summary of what we expect is likely coming from

the CDC in their doxycyclin postexposure prophylaxis or pep guidelines uh where

there's a recommendation based on um a highquality evidence that doxycycl 200

milligrams taken once orally within 72 hours of sex um can be considered for

gay bisexual and other men who have sex with men including transgender women uh

who are at higher risk for STI uh or as defined by having a history

of at least one bacterial STI in the prior 12 months so a lot of information

there but that is the population that CDC is looking at recommending doxycyclin pep for um based on studies

that I will be showing you here in the subsequent slides there is no recommendation they have the second uh

row here we expect that they will release guidance that there is no recommendation given at this time for

the use of doxy cyclin pep in cisgender women cisgender heterosexual men

transgender men other queer and non-binary individuals if this intervention is offered it should be

implemented with considerations for ancillary Services as detailed Below in their guidance so this is not a

recommendation against using doxy cyclin pepep for these other groups just

acknowledging that there is insufficient evidence for a strong recommendation for docy cyclin pep in these groups so this

is again draft doxy cyclin pep guidance which we expect is coming from CDC very

soon uh in the next month or two months or three months hopefully um and what I

wanted to do was just take a little bit of time and walk through three studies um which uh published studies which um

this guidance is largely I think being based off of and so first let me apologize that the the next few slides

are going to be a little bit text heavy and data heavy um but I think it's important um information so the first

study to really look at this and be published was a randomized study published back in I think it was 2017

2018 in the lanet um where they did a subgroup study so it was an amended

study um of high-risk menual of sex with men that were originally studied to

conduct that was originally conducted to study the efficacy of HIV prep that's

you know prevention of HIV with the use of tenopir and emtricitabine which many people know as

under the Brin name travada but they took a subgroup of this larger study uh

and looked at the efficacy of doxy cyclin pep um in France at preventing

bacterial STI so this was a a study conducted in France it was an open label

study meaning participants knew if they received doxic cyclin or not um and

participants had to be adults either um men who have sex with men or transgender

women having sex with men uh they were HIV negative right because they were all initially being studied for HIV prep and

they had to be at high risk for HIV acquisition um and so they were randomized to doxy cyclin versus a

standard of care and with the doxy cycl pep group uh that group was instructed

to take 200 milligrams of doxic cyclin um in a uh once within 24 hours but no

later than 72 hours after each high-risk sexual event and the they instructed

participants to take no more than three doses per week um they studied the

occurrence of a first bacterial STI and they combined chlamidia gonorrhea or

syphilis into one primary outcome measure they followed up these patients every two months with testing for

chlamydia gonorrhea and syphilis uh testing for chlamydia and gonorrhea was conducted through throat and rectal

swabs and urine um and they also assessed doicy adherence and in the

table at the bottom uh you can see uh the followup that they had the numbers of people and the proportion that

followed up um every couple of months for the different groups and you can see that followup was uh pretty high across

the study and so what they found uh and what I'm showing here are the camplan Meyer

curves from their analysis uh in the upper left you have chlamidia Gara or

syphilis combined as a single metric in the upper right goria and then in the bottom chlamydia and syphilis and so the

blue lines are those who were on doxy cycl pep the red lines in each graph are

uh the participants that did not receive pep and the graphs show the cumulative

probability of the STI that's being analyzed and in each graph I've and in

each graph I've highlighted the hazard ratio and so essentially what these graphs show the one in the upper right

is they found a 47% reduced risk of a new bacterial STI in the doxycyclin pep

group that's you know chlamidia ganara or seis uh 47% reduced risk they found

no reduced risk um of G of Gonorrhea in the doxycyclin pep group as shown in the

upper right and then uh across the bottom with chlamidia and syphilis 70 and 73% reduced risk of chyia and

syphilis respectively um and so the the overall findings of this 47% reduced

risk of a new bacterial STI largely was driven by the reduced risk for chlamidia

or syphilis um in people who received doxic cyclin pep so pretty significant risk reduction

with the use of a single dose of doicy after a high-risk sexual event um a few

other important findings here majority of goria and chlamydia was detected from

rectal and throat swabs as previously highlighted by Dr Alamar this highlights the importance of testing and screening

at all sites of sexual contact 71% of STI that were diagnosed were

asymptomatic again consistent with Dr Al with what Dr alamari showed previously and highlights the importance of

screening and then doxic cycl adherence they measured through a number of different measures um during the clinic

visits about 83% reported taking doxy cyclin within 24 hours of a sex encounter when they measured um plasma

concentrations um they only detected doxic cyclin in about 30% of the pep

group recipients the caveat here being that the plasma test they did was only

able to detect doxycyclin use in the previous 48 hours so not a great test of

doxycyclin exposure if the test only picks up doxycycl use in the last two days um and then what's also important

of note with compliance and adherence is that um 63% of participants in the doxy

pep group and 25 % of those in the non-ep group had at least one plasma

sample with doxic cyclin detected so there were a potentially substantial number of people in the um comparison

group the non- pep group that were found to also be taking doxy cyclin which

would have um potentially watered down their results and yet they still found a statistically significant risk reduction

uh for prevention of chyia and syphilis with using doxycyclin pep

um of note the study did not assess the impact of the use of doxic cyclin on

antibiotic resistance subsequent Studies have however done that um so what I'm going to show you now is probably one of

the um main articles and studies uh that is that has been um conducted and used

to develop cdc's um draft doxy cyclin pep guidance this is a New England

Journal of Medicine article that was just published in about a year ago April of last year um it was also a randomized

open label clinical trial conducted in the US this time specifically at HIV and

sexual health clinics in San Francisco San Francisco in Seattle um the participants were very similar to the

the prior study so adults um men of sex with men or transgender women having sex

with men um people taking HIV prep one difference here is that they included

HIV positive individuals um and then uh participants

were also at high risk for HIV and high risk for STI as defined defined as a

person who was diagnosed with a bacterial STI in the previous 12 months that if that sounds familiar that's

because that's what was incorporated into cdc's draft um and potentially upcoming uh pep guidance they were

randomized 2: one people in the doxic cyclin pep group again were instructed to take doxy cycling 200 milligram by

mouth once within 24 hours but no later than 72 hours after each high-risk

sexual contact the difference this time is that they they had a maximum of once every 24 hours remember that in the

prior study they uh the maximum was three times per week in this study uh

they allowed a maximum of once every 24 hour uh use of uh or dosing of doxic

cyclin they had an number of different outcomes um again the the primary outcome here being studied was the

occurrence of at least one bacterial STI that's goria chlamidia or syphilis each

quarter so they followed these individuals for 12 months with quarterly scheduled clinic visits where they did

testing and so they did their analysis by quarter and so if a person was diagnosed with multiple STI in a single

quarter that person only contributed to the analysis once per quarter so an

important sort of caveat to keep in mind they also study tetracyclin resistance

in ganaria isolates as well as staff orius isolates we'll talk more about that um and at each Clinic visit they

did chlamidia goria and syphilis testing uh again similar to the prior study they took swabs of the throat and rectum and

uh collected urine samples for the chlamidia and ganara testing they access dox they assessed doxic cyclin adherence

um and then what was new in study is that they took swabs of um participant naras and Oro ferins uh to try and

culture staff orus so they were looking for staff orius colonization and they

did doxic cyclin resistance testing on those cultures and of note the study was

stopped early because of um the effectiveness of doxic cyclin postexposure

prophylaxis when they did the analysis they did the analysis by two different cohorts this is the prep pep cohort so

this is showing the results of um doxy cycl pep in participants who were on HIV

pre-exposure prophylaxis that's the trva andaban prep um and what you can see is

they broke it out by um any STI and then um the bottom part of the uh chart here

uh garia chlamydia and syphilis and so what you can see is on the right hand

side where I highlight the uh uh risk ratios is that the doxycyclin pep group

uh showed a approximately um 2third or 66% reduced

risk for the diagnosis of any STI as highlighted by that relative risk number

of. 34 and you can see then you know for any ganaria any chlamydia or any early early

cus infection that there were also significant risk reductions with the use of Dr cyclin pep um when you get to the

chlamydia and syphilis levels you know we're talking um 87 88% reduced risk of

chamian syphilis individually with the use of doxic cyclin Pep so pretty

substantial significant reductions in the risk of these STI both combined uh

as well as individually including with gonorrhea they also did a separate analysis for participants living with

HIV um you can see that they found very similar uh risk ratios um and risk

reductions with the use of doxic cyclin Pep um tetracyclin resistance uh they

evaluated tetracyclin resistance in ganaria cultures and staff orius cultures the graph I'm showing here on

the Le hand side is um looking at goria cultures um there's a lot of information

in these graphs um which might be a little confusing um in parenthesis at the bottom under each um you know

Baseline versus doxic Cycling group versus standard of Care Group they're showing the total number of um cultures

that were obtained and in the bars they show the percentage of and the number

and percentage um of those cultures which came back showing uh resistance

and non-resistance so they had culture growth in a minority um that uh showed

resistance in the dark blue bars and non-resistant gonorrhea in the light blue bar

um and you can do sort of simple math to uh determine that about 27% of ganara

isolates that were cultured at Baseline were resistant to

tetracyclin um and when you look at the proportion that were resistant between

the two study groups uh 38% resistant versus 12% resistant uh there was a

difference there in the proportion um of ganara results that were uh resistant

tetracyclin the clinical significance of this is a little bit unclear because as Dr alamari highlighted um tetracyclin is

not a recommended antibiotic anymore for treatment of um

Gara when they when they looked at staff orus cultures so very similar graph but

um a little more confusing here perhaps um you can see that at Baseline 12% of

Staff orius cultures showed resistance to tetracyclin and between the two study

groups at 12 months um into the study in the doxic cyclin pep group 16% of Staff

orus cultures were resistant to tetracyclin versus 8% uh in the standard of Care Group now that also is a higher

proportion that were resistant to tetracyclin but what's also of note is

that staff orus Carriage Carriage was 40% lower in the doxy pep group versus

standard Care Group at 12 months so there a little bit of a trade-off because there was less Carriage uh

detected in people uh but uh slightly higher resistance in the doxy cyclin pep

group again hard to know um the clinical significance of

this um 30% of participants had an STI

diagnosed at enrollment so high proportion who came into the study with an STI that had to be that was diagnosed

and treated um 86% of participants in the doxy pep group reported taking doxy

cyclin consistently um and they also had a number needed to treat that they calculated uh of about five so that is a

pretty low number needed to treat number so in summary um doxy cyclin pep taken

within 72 hours of condomless sex decrease Gara chlamidia and early

syphilis by about 2/3 among menu of sex with men and transgender women doxic

cyclin pep also substantially reduced the occurrence of each bacterial STI

individually including gonorrhea so when you look at syphilis it was about a 77 to 87% reduced risk with the use of doxy

cyclin pep with chlamidia 74 to 88% reduced risk with doxycyclin pep and

with goria 55 to 57% reduced risk with doxic cyclin

pep um now one of the questions is well why do they have a significant reduction

in goria in this study but not in the prior study conducted in France um and

there is some explanation behind this you know tetracyclin resistant gunara was more prevalent in France when the

prior Lancet article study was conducted um compared to Gar tetracyclin

resistance resistant ganara in the US it's about 56% versus 20% uh resistant

ganara and this may partly explain the different ganaria findings in the two studies and this becomes important

because the final and third study I'm going to show you um has that that that fact goria

resistance factors in as well so in the last few minutes let me highlight this final study um looking at doxic cyclin

postexposure prophylaxis to prevent STI in women so this is again a randomized

open label clinical trial of women 18 to 30 years of age in Kenya were not

pregnant and were receiving HIV prep therapy they were randomized one to one

to receive doxy cyclin postexposure prophylaxis or standard of care um and

similar to the last study uh the doxy pep group was instructed to take um

doxic cyclin 200 milligrams um orally once within 72 hours after each

condomless sexual encounter with a maximum of 200 milligrams or you know one dose per day

um again they tracked the occurrence of any bacterial STI each quarter so similar to the prior study a person with

multiple STI in a quarter contributed to the analysis only once they similarly

followed uh these women for 12 months with quarterly clinic visits they assess

doxic cyclin adherence um at the visits and also by weekly text messages and

interestingly they also collected hair samples to test for doxy cycl exposure

and uh each hair sample represented about a month of exposure they importantly also did molecular

resistance testing to detect doxy uh tetracyclin resistance um in ganaria and

chlamidia isolates and what they found was uh no significant risk reduction in

any STI or chlamydia or ganara individually um so the incidence of

bacterial STI was not significantly lower in the doxy pep group compared to the standard of Care Group there was

only one syphilis infection identified which prevented sort of separating it out in the analysis um and importantly

100% of ganaria isolates um showed tetracyclin resistance compared to no

chlamydia isolates had tetracyclin resistance and so this likely factored in to the ability to show um any

statistical significance um with you know Gara individually or um you know in

combined endpoint um there were also issues with um doxy cyclin compliance so

despite about 80% of participants in the pep group reporting doxic cyclin use um

when they did hair sample testing doxy cyclin was only detected was detected in

at least one visit in only about 56% of participants and when they excluded

participants where doxy cyclin was on hold for example if a woman became pregnant

they had to hold the doxic cyclin or if there was concern for pregnancy they had to hold the doxic cyclin um well they

assessed when they excluded visits where doxic on doxy cycl was on hold uh doxic

cyclin was only detected in about 33% of visits so the this study um found that

the incidence of bacterial St eyes was not significantly lower with doxy cyclin

pep compared with standard of care in women receiving HIV prep in Kenya um and

importantly hair sample testing to assess doxic cyclin use suggested that doxic cyclin was not taken during the

majority of months and on top of that doxy cycl resistant Gara 100% of

isolates showed resistance likely impacted the ability to show efficacy so

those are the three primary studies which um are published studies um which

are um the basis for cdc's draft doxy cycl pep guidelines as shown here this

is what I highlighted previously this is why the the focus is of these guidelines

is in men who have sex with men and transgender women who are at higher risk for

STI um but this guidance um as it was last reviewed here um does not exclude

the possibility of um using doxy cyclin pep in other populations it's just that

there is insufficient data and um more study will be needed and there are

additional recommendations and ancillary Services which become important when um discussing and counseling patients

including screening for other STI as Dr Alamar highlighted risk reduction

counseling um you know having that discussion about the the risk and the benefits of doxy cyclin pep assessing

for HIV prep pre-exposure prophylaxis and vaccination for other um STi for

which there is a vaccine available um so we don't have a lot of time left um but

let me just maybe see if Dr alamari wants to make any comments I know um the

providers are already starting to use doxy cycl pep um clinically um given the

data given the draft guidance that um has been put out and we expect more formal guidance to come shortly but let

me um just see in the last minute or so if Dr uh uh Dr alar has any comments about how this has been implemented uh

clinically in her clinic or in other um provider clinics yeah thanks Dr Chan

this was a great overview of all the various studies that have supported this upcoming recommendation and I have to

say that you know the patients are also hearing about this through various

networks um and so they've been asking more like hey should I be on docy pep

and so right now we've actually been doing it on an individual kind of risk assessed basis um I have several

patients that are on it um and uh there's you know a lot of um counseling

to go with it you know this doesn't obviate the need for barrier protection

um it doesn't help all SDI so there's a lot of kind of the general counseling that you have to give no matter no

matter what including you know when prescribing HIV prep I think we talked about it again actually at our team

meeting today and the concern that was raised I think by someone else in the chat was are we worried about antibiotic

resistance and I really do think there's some hesitancy especially given the data you showed that you know we we could

create more resistant bugs if um if this was blanketly used for everyone on the

other hand we could be preventing a lot of unnecessary sexually transmitted infections so I think there's a hard um

line a fine line to walk right now and so I don't think people are universally

recommending it for sure and obviously the be guidance on strict indications but it's the word is out there and

patients are definitely asking about it great that's very helpful thanks so much for your um input thank you to all

uh participants um there's a lot of information here uh thank you very much to Dr Alamar for um her clinical review

and um comments here at the end and just as a reminder these slides and the

recorded webinar will be posted online on this website afterwards uh so you and

others can go back and review not only this webinar but also the syphilis and congenital syphilis webinar we had back

in December so we're a minute over time let me um stop and thank you all for your participation uh and we will see

you back here again uh next month thank you all very

much