When to start antiretroviral therapy in pregnancy
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
