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Antiretroviral Therapy During Pregnancy and Delivery: 2015 Update

welcome to the NWA e.t.c project echo

I'm Kent unruhe and I'd like to turn it

over to dr. Brian wood our medical

director for the talk today thanks Ken

thanks everybody for coming great to see

everyone what we're gonna do today is a

bit of an update on perinatal treatment

in particular I'm gonna focus on an R at

antiretroviral therapy maternal

antiviral therapy so during pregnancy

and delivery with an update from the

most recent guidelines and one other

fairly recent paper so this will be a

little bit of review and an update and

I'll ask everybody to weigh in on the

end

regarding what regimen you think is best

for a pregnant woman right now in 2015

so if you get ready for a poll question

at the end with your mobile device or

another window that'd be great maybe

I'll ask everyone here to weigh in as

well so these are the most recent

guidelines down at the bottom is where

you can find them at AIDS info dot NH

gov the perinatal treatment guidelines

were most recently updated in August I

just wanted to start the guidelines open

with national objectives I just want to

start with a few numbers and I think

numbers are helpful in terms of

counseling pregnant women or service

discordant couples regarding risk of

transmission to the infant nowadays in

2015 with potent antiviral therapy what

are the current estimates of

transmission risks and what are the

goals so the guidelines open by saying

due to advances in screening and

treatment perinatal transmission has

dramatically diminished to 2 percent or

less in non resource-limited settings

and the CDC's goals are to reduce this

even further to an incidence of less

than one infection per 100,000 lives

live births and a rate of less than one

percent among HIV exposed infants a

couple of interesting papers note recent

estimates of viral transmission and sort

of introduced the idea of the importance

of maternal viral load in terms of

transmission risk so this first paper

from the UK and Ireland looked at over

12,000 infants born HIV infected mothers

and found an overall perinatal

transmission rate of 0.46 percent in

2010 and 2011 overall and I think this

number becomes useful for giving women

estimates with adherence antral therapy

and a viral load less than 50 copies

rate was estimated at point zero nine

percent or at a viral load of fifty to

three hundred ninety nine copies an

estimate of one percent and that starts

to show the importance of maternal viral

load and I'll turn more to that here in

just a sec also a slightly smaller study

from Canada looked at over 1,700 HIV

infected pregnant women from 97 to 2010

overall transmission rate of one percent

in all mothers receiving a RT 0.4

percent if more than four weeks of a RT

received and a couple important points

I'm gonna return to here the importance

of maternal viral load and the

importance of starting a or T early and

really getting the viral load suppressed

during pregnancy this is a slide I've

shown before this is not new data this

is an older paper but I just really

think this emphasizes the importance of

maternal viral load in terms of

transmission risk so I recreated the

graph in this slide which was based on a

cohort of 94 live births this is data

before the era of potent combination AR

T and you can just see very clearly

higher maternal viral load near time of

delivery much higher risk of perinatal

transmission if we go all the way down

here to not detected this is sort of

extrapolated from their data an estimate

of less than 2% if viral load is

suppressed near time of delivery so just

really want to emphasize the importance

of maternal viral load in terms of risk

of transmission to the infant and I

think the pendulum is really swinging

towards starting a or T as early as

possible giving the pregnant women as

much time on air T as possible and

really trying to make sure the maternal

viral load is routinely suppressed by

the time of delivery now this study this

is not in the guidelines but I just

thought I'd share this this looks at

factors associated with a detectable

maternal viral load at the time of

delivery this is a study from Ingrid

Katz at Harvard they followed 671 HIV

infected AR teen naive pregnant women 13

years or older at 67 sites in the US and

Puerto Rico so this is again data from

non resource-limited settings from 2002

to 2011 looked at how many women had a

detectable viral load at delivery which

in the end was about 13% of participants

and then the point of this in

this was really just to assess factors

associated with a detectable maternal

viral load at delivery and I'm just

going to share this because I think

there's some important points here so

these are all the factors that were

statistically significantly different

between women who had a viral load above

400 copies at delivery and those that

did not and the factors significantly

associated with a viral load over 400

copies at delivery were being

multiparous of blackest ethnicity of a

lower education level a or T initiation

in the third trimester and I mistakenly

left out the percentage here was twenty

three point nine percent of women who

started AR T late in pregnancy in the

third trimester had a technical viral

load at delivery so really sort of

emphasizing the importance of starting

early if the first prenatal visit was

not until the third trimester a third of

women had a detectable viral load at

delivery if there was at least one

treatment interruption or not

surprisingly if there is any report of

non adherence there are much higher

percentages of detectable viral loads at

delivery which is really what we want to

try to prevent in order to reduce the

risk of transmission to the infant as

much as possible really want to

emphasize the importance of early

prenatal care starting woman early on AR

T and then this sort of gets at other

factors for which you might want to

really emphasize adherence and adherence

support and it really sort of target

your resources towards supporting women

with adherence during pregnancy so the

conclusion of this paper

so overall thirteen point one percent of

women who initiated AR T during

pregnancy had a detectable viral or

delivery we really want to make efforts

to get that down timing of AR T

initiation and prenatal care was a very

important factor towards predicting

detectable viral load at delivery and

certain social factors like ethnicity

and education level may help identify

women who could benefit from focused

efforts to promote a or T initiation

adherence so that that's not mentioned

in the guidelines I just want to share

that because I think it really

emphasizes the importance of starting AR

T early the importance of adherence and

the importance of maternal viral load

and certain individuals who may need

more adherence support I think again the

pendulum is really swinging towards

starting AR T early and there's day

the higher the number of weeks a woman

is on air T before delivery the more

likely she is to have a suppressed viral

load I think there are certain factors

we need to consider in terms of timing

if a woman presents in the first

trimester we think about baseline viral

load we think about how she's doing

clinically if she's really struggling

with vomiting and things like that it

may make sense to wait but the

guidelines are really emphasizing more

and more starting early even starting

before the genotype results are back and

I think the later in pregnancy alone

presents the more urgent it is to start

a RT before you have genotype results

but the other graph I'd like to share

just to give a sense is this is also a

graph I recreated from an older study

but just really to emphasize where the

risk of perinatal transmission is most

is sorry it's highest during pregnancy

so this is a modelling study to just

estimate just estimated if you have a

hundred HIV infected pregnant women here

are the estimated number of infants

without this without a RT who would

become infected at each stage of

pregnancy so in the first 14 weeks only

114 to 36 weeks for and then this

becomes the period of highest

transmission risk 36 weeks through labor

and intrapartum ends up being the height

is highest and then the risk of

breastfeeding so overall without a RT

out of a hundred HIV infected women be

predicted 41 infants would end up being

infected again this is without a RT and

this is in the setting of breastfeeding

for this reason in this recommendation

has not changed on recent guidelines

still recommended that hiv-positive

pregnant women do not breastfeed in this

country as we've talked about on echo so

with that I'll turn to the most recent

pre that most recent guidelines for

preferred agents in pregnancy and I'll

just highlight this table from the most

recent guidelines so we'll do preferred

agents and then alternative and then

agents with insufficient data so I've

just broken this into the NRT eyes you

now have three options for preferred

agents with two Nava V R plus M

tressider beam or lamivudine a back aver

with with lamivudine which of course has

the asterisks which we always have with

the back of here that b5 701 must be

negative when you combine a back of Erin

there's the asterisks based on five 2:02

that really should not be combined with

a fav earns or atazanavir especially

with high viral loads of ire load over a

hundred thousand and then there's of

course as i da beating or a ziti with

lamivudine and then preferred and RT n n

RT i a Fabrice is still listed of course

with the big asterisks that there it is

controversial whether a Fabrice is trial

genic and whether it affects neural tube

development I think there's a lot of

newer data suggesting that concern may

have been overblown and there may not

actually be that much risk but the

current recommendation is still if you

have a woman with HIV of childbearing

potential who's not using reliable

contraception not to use a trip lobe but

if a woman gets pregnant on a trip Allah

usually cats out of the bag neural tube

has developed if she's doing well and

tolerating it there's no urgent need to

switch it the preferred i n st eyes or

integrated strand transfer inhibitors in

pregnancy our route is route tegra vir

excuse me and then darude boosted or no

vir has moved up as a preferred P I

along with boosted atazanavir the other

change that happened with this most

recent guidelines is rope every move

from insufficient data up to being an

alternative agent it of course just like

in the absence of pregnancy has the

asterisks that it should not be used if

cd4 count is very low or viral load very

high and then these other agents doggie

Tiger beer albeit egg revere most

notably are still listed as insufficient

data for use in pregnancy I think data

is accumulating on those and I do think

that in the future the pregnancy

guidelines are likely going to follow a

similar pattern as the adult treatment

guidelines and likely as we get more

data for the new grades inhibitors I

think those are going to become first

line and I do think nowadays if a woman

becomes pregnant on Truvada dolly tag

over or on straw build is tolerating it

is suppressed I do not think there's an

urgent need to switch it and I think

that as we gain more data these will

likely move into becoming preferred

agents you know I just want to bring up

here some advantages and disadvantages

and pose this question to you and I'll

ask you all the way in on this at the

end what is the optimal AR T regimen for

an HIV infected pregnant woman nowadays

in 2015 with all of our options and all

we know and I just made this table based

some date of some comments from the

guidelines and some other comments just

in terms of advantages and disadvantages

and I'll present this for the backbones

and then the next slide for the anchors

and I'll ask you what you think is the

best regimen treatment naive pregnant

woman no resistance let's say good

adherence all options at hand what do

you think is the best so in terms of the

backbones you know with Tanaka v r+

lamivudine around her side of being

daily dosing overall very well tolerated

there are of course concerns about

Tanaka vir with renal insufficiency as

in general there always are and then

there is this concern we don't really

know how to Navi affects fetal bone

development the study we had shown that

did DEXA scans one time on infants and

found lower bone mineral density if

exposed in utero to Tanakh fear was just

published just a couple weeks ago but

again as we've talked about here on echo

we really don't have longitudinal data

to know if that is clinically relevant

so I think the jury's out on how to not

fear affects fetal bone development and

whether it's clinically significant or

not well the back burn in the movie Dean

again we have daily dosing overall well

tolerated and then they're the same

caveats as always to a BAC aver do not

use it b57 on positive data for

cardiovascular risk mixed and

controversial and then with diving in

lamivudine of course there's a ton of

clinical experience in pregnancy but you

go to be ID dosing relatively more side

effects and lower tolerability in terms

of the anchors you know raw tegra fear

of course is well tolerated few drug

interactions we know that integrate

inhibitors lead to a very rapid decline

in viral load we really don't know if

that's clinically relevant or not with

rajbhog refer I think the biggest

downside is the BI D dosing and then we

do have a lower barrier resistance

compared to for example the boosted P is

you know favron 's daily dosing but I

think as we've talked about with the

adult treatment guidelines it's really

fallen off the list of preferred agents

for starting because of the worsening

mental health side effects I do worry in

pregnant women with the risk of

postpartum depression about the use of a

Fabrice and worsening that so I think it

has limitations boosah has a nevere we

do have a lot of experience in pregnancy

it's once per day but of course there's

the risk of hyperbilirubinemia

kidney stones interactions with antacids

which can become very relevant in

pregnancy and the

de Mille dose in late pregnancy is still

unclear whether or not you increase it

or not and then I boosted River has

moved to a preferred agent but I think

the jury's still out on the best to ruin

if you're dosing in pregnancy the

guideline still recommend B ID which i

think is a limitation there have been

some small studies suggesting Daly might

be adequate in pregnancy although just

in Jayde's at the start of September

there was a study suggesting that we

still need we do really need B ID in

pregnancy so I think boosted Revere has

moved up referred but a big point here

being it really should be twice a day if

you're going to use it turning then to

inter-parliamentary biotherapy so first

you know the recommendation always is to

continue antic partum a RT on schedule

as much as possible during labour or

before c-section and as we've talked

about with IVs i da BD nor AZT the

current guidelines are that it is

definitely indicated if maternal viral

load near delivery is over a thousand

and I'll show you here in a second where

that came from and that recommendation

is still in line with the recommendation

for c-section for HIV indication it's

still have over a thousand c-section is

certainly indicated and the guidelines

say intravenous W near AZT is not

required if the woman is receiving

routine ere t viral load consistent

consistently suppress or below a

thousand but as we've talked about here

that is a little controversial and I

would say if there's any concern for

adherence near delivery if I were loads

detectable at all I think most providers

would have a very low threshold to go

ahead and give IV AZT because there's

very little downside I'll just end by

showing you this data for where this

recommendation for IV AZT came from

because we've talked about this

recommendation but I don't think we've

ever presented this study and then I'll

ask you to weigh in quickly on what you

think the optimal AR T regimen is for a

pregnant women with women with HIV these

days so this is from the French

perinatal cohort they have been

enrolling nearly every hiv-positive

pregnant woman in France since 1997 they

analyzed a total of almost 12,000

deliveries here's a list of the AR T

exposure the woman received during

pregnancy so in the early days about 10%

overall received a ZT

18% dule RT 72% triple-a RT and in the

end of those almost 12,000 deliveries

95% received IV AZT and just here's the

graph of parent mother-child

transmission based on viral load and

receiving AZT in the green bar or not

receiving AZT in the blue bar and we can

see here is there's really no difference

at viral loads under 100 sorry excuse me

under 1,000 copies and these differences

here were not statistically significant

and where the statistically significant

difference came out was if maternal

viral load near delivery was over a

thousand copies and this is what led to

the most current recommendation the

perinatal guidelines that if maternal

viral load is over a thousand year

delivery absolutely IV AZT is indicated

not necessarily indicated at lower viral

loads though again many providers would

have a low threshold to go ahead and

give it especially if there's any

concern about delivery last point before

I ask you to weigh in is if you are

following a pregnant woman with HIV it

is worthwhile to go ahead and contact

the and Roy brown pregnancy registry and

just go ahead and report the air v's

that she is receiving this is how we

accumulate data and know that a RVs are

safe it's a fairly easy and painless

process and I would encourage you to do

that so with that I'll ask you to just

open up a browser window or your mobile

device maybe I'll ask my colleagues here

as well and I'll just pose this question

and I've give you a few options what do

you think nowadays let's say treatment

naive early pregnancy you've got all

options available to you what do you

think is the best regimen what would you

suggest someone let's say patient comes

to you and says I'll do whatever you

recommend what do you think is the

optimal airView regimen during pregnancy

so a so dog-eating which is a ZT

lamivudine which is 3dc and boosted as a

no barrier B to not very mature side of

being which is Truvada

and boosted as a Nabire C to not very

mature side of being a real tiger vrd2

not very mature side of being and doll

you Tiger beer which again is

insufficient data but we're using it a

lot in non pregnant patients or

something else I didn't come up with why

don't we give that one more second and

then we'll see the poll and we'll have a

couple minutes for questions before we

turn to cases all right thanks everybody

for weighing in why don't we go ahead

and broadcast that I'm curious to see

the results all right so I good spread

there which i think is really good to

see I it reminds me that we do have a

lot of options and there is no one right

answer but it looks like almost 50

percent said to not forum tressider

being plus real take over I think that

is a really excellent option especially

if you feel confident a woman can take B

ID meds very few side effects

very few drug interactions I wonder if

it looks like maybe one person picked

something else