start

When to start HIV Therapy? When to Switch?

give us what you what you've learned or

what you're learning alright well just a

few months ago at a CAC idsa we heard

the results of the na Accord study which

was this big conglomeration of clinical

databases that tried to imitate a

clinical trial that was randomizing

people to either start above 350 or wait

till they had fallen to a CD for below

350 and that study showed a seventy

percent greater mortality if you waited

until after you were below 350 and the

investigators at that time promised that

at Croy they were going to present

further data looking at the question of

500 and that's what they did at this

meeting so the idea of the studies you

take this observational database of

people who enter the study with cd4

counts above 500 and you you look at

those who start within a year and a half

of first meeting that criteria or those

who don't and you sort of think of the

first group as the people who are

randomized to the immediate group if you

will in the second group as the people

who are randomized to the deferred group

and what they found was again a sixty

percent decrease mortality and people

who started after their city above 500

as opposed to waiting to below 500 this

of course is not the same as a true

randomized controlled trial where you

actually randomized people to take

treatment early or late it's attempting

to imitate that trial but of course with

an observational study there are a lot

of potential confounders you know people

who start early may be very different in

many ways from people who decide to wait

and that always is a problem with

observational data on the other hand

these investigators have done as good a

job as you can do in trying to eliminate

those confounders and so I think it's a

very sophisticated technique and the

question is just whether people will buy

data from an observational study like

this as being an acceptable substitute

it goes the wrong trial and there is a

there's a trial that has been funded to

look at this question but of course it's

going to be an expensive time-consuming

trial and are we willing to wait that

long for the results so it'll be

interesting to see how this plays out

in terms of the acceptance of these

results I will say that they're not the

only study to show a benefit to early

therapy there have been a number of

other observational studies that have

also shown benefit but when you get up

to this level of 500 you know it becomes

harder and harder to show a difference

and not all the trials have or not all

the observational studies have shown a

difference in that level you wanted to

cover the switch mark and Markson and

can you talk about yeah yeah so they're

actually haven't been a whole lot of

clinical trials at this meeting which is

a little unusual I usually I come here

and I talk about trial x and y and z and

haven't been a lot of those but there

was one important trial to switch mark

study and and this is a study of

raltegravir I centrist and we've now

seen several something mark studies we

saw the benchmark and then the start

mark so bench martin's relative air and

treatment experience patients then start

marking naive patients so now switch

mark took people who were doing well on

a protease inhibitor based regimen and

switched them to ral Tiger bear versus

staying with their protease inhibitor

and what they found was that while their

lipids got better with the switch there

there were more biologic failures that

people were actually better off staying

with their protease inhibitor frankly I

think that was two entirely predictable

because what happened was they let

people into this study even if they had

previously failed other regimens and so

a lot of them probably had nucleoside

resistance and when they're when you're

switching from a boosted bi which is a

has a pretty big barrier to resistance

to rotate over which is a very potent

drug but but is fragile in the sense of

mutations and doesn't take a lot of

mutations to get resistant you know if

your nukes aren't adequate you've just

gone from a pretty potent regimen to one

that is fragile so they weren't

optimizing treatment right exactly and

and I don't know why they just chose to

do the study that way most which studies

they take people who are on their first

regiment no history of failure switch

them from a pi/2 real tiger burrow if

they've done that it would probably been

fine but it was the inclusion of those

people who weren't weren't on good nukes

I suspect that caused this problem and I

although I it's it's too bad

they did it that way I think we can

learn something from this and that is

that with all this enthusiasm for I

centrist right now we've got to remember

it's not you know it's a great drug but

it isn't a super drug I mean it has its

weaknesses and the most important

weakness is that it really needs to be

flanked by other good drugs we learned

that from the original

treatment-experienced patient studies so

i have seen in the community that people

are just thinking oh wow I love this

drug patient doesn't like drug acts

switch them to this doesn't like drug

why switch them to the we've we've done

that that's the [ __ ] I learned by

now everybody's been saying it's the

drug to sure I've got to be on this I

mean I'm sure you've had people to come

doc I really want this drug because Joe

is doing this and Joe and Sally or

whoever and and you and you've got your

infinite gut feeling and wisdom and

science and and yet you're having a

person that's based upon popularity

saying they want to be on the drug

d'azur and how do you how do you talk to

a patient how do we tell people that

that this is this is really serious

stuff because you maybe have one chance

to move to a combo that you may be on

for a very long time I mean we talked

about 8 10 15 we don't know maybe 15

years and and you have to really think

very very seriously because this is this

is not the old days of the the switch to

this and i'll try this maybe I'll remove

this up and I'll add something else I

mean those there's a pretty pathetic

days when we had that that mono infinite

or what they call it virtual not other

charity there or switching from one

thing to another just made it that right

right we have i shouldnt be doing that

anymore it's tragic when i see it happen

i just recently saw a patient who came

to me who was on truvada and I centrist

and was failing miserably had complete

resistance to integration Hitler's and

he had been heavily

treatment-experienced had resistance to

everything so they're putting him on a

regimen that has basically been looked

at in completely treatment-naive

patients it doesn't how could you think

that it would work for this poor guy but

so so I think we really have to remember

that as good as this drug is you will

really use it up fast and waste it if

you don't think about the rest of the

regiment

and it's the same would be true for a

non-nucleoside you know it's we've heard

this before for many other classes of

drugs there's nothing new about about it

with rel tigra but but we don't want to

repeat the mistakes of the past and the

only other thing I think you were

interested in and I am really interested

in as a new boosters this is really

exciting as you know the current

standard for using any protease

inhibitors to combine it with with the

low dose of rotana vera norvir to try to

boost the drug levels of the protease

inhibitor we don't use rotana beer

anymore for its own antiviral effects we

use it strictly as a pharmacologic

booster but but it does have side

effects it has some GI side effects it

can increase cholesterol and

triglycerides it can sometimes cause

some insulin changes or glucose

metabolism changes so and it's expensive

so there's been a lot of desire to get

away from that use to find a new booster

that doesn't have all of those issues

and that is heat stable and can be Co

formulated with other drugs was right

now the only the only drug that Co

formulates rotana beer is Calitri so

there's a number of companies working on

these boosters Gilead has one and their

interest of course is because they're

their new integrase inhibitor of I tiger

beer has to be boosted and they would

love to have their own booster instead

of having to work with rotana beer so I

think everybody in the room was quite

surprised to hear that they had already

developed a CO formulation that includes

two nevere FTC albeit egg river and

their new booster a fork pill Co

formulation that's already starting in

clinical trials and so far you know very

short-term studies looks like it works

at least to boost albeit egg Revere it

looks to be well tolerated and they're

going to go forward in phase 2 study so

that's very exciting so that would be a

logical you know first-line alternative

to a triplet one pill contains all of

these drugs now their drug could also in

the end be used to boost protease

inhibitors as well but they're obviously

focusing on albeit a goober but they're

saying that they're going to make it

available for boosting of other drugs as

well and then Sequoia has a drug that

they're looking at that they've been

studying to boost protease inhibitors

and that also looks promising there I

was a little concerned about the side

effects in their short-term studies some

headache nausea vomiting things we don't

like to see but but anyway that's that's

going forward so you know there may come

a time when we have a number of

alternatives to to return of here