- You may have heard the term HAART
referring to HIV treatment.
But what exactly does that mean?
Well, HAART, which stands for
highly active antiretroviral treatment
refers to the sort of modern day, present
treatment regimen for treating HIV infections.
And it's called highly active
because compared to the previous treatment regimen,
HAART is just a lot more effective
and so the name just kind of stuck.
So before we give just one type of drug
to help control an HIV infection,
we usually give an NRTI
which stops the reverse transcriptive step
and infection of a CD4 cell.
But, you know, HIV likes to mutate a lot
and it turned out that when only one type of drug
was given for an infection,
the HIV would eventually become resistant
to that type of drug.
So, of course, the drug didn't work anymore
and the person's infection would almost sort of
pick up where it left off
it would start to worsten again.
Except this time, almost more aggressively in a way
because now it would be resistant
to that original type of treatment.
But in comes HAART,
highly active treatment.
And you know, it's not that we're using
totally different drugs, I mean,
sure we've got a few more types at our disposal now,
but the key thing is that nowadays
we know that if we give two or three drugs,
which is what we usually do in HAART.
So if we give two or three drugs,
instead of just one,
the HIV infection can be really well controlled.
And what do I mean by that?
Well, each of the drugs in a particular HAART regimen
works in a slightly different way,
stopping HIV at different points
during its replication.
So these drugs used together
are really effective at preventing HIV
from making copies of itself.
It's life cycle just won't be able to continue,
so new varions just don't end up being made.
And you know, if we do encounter, by chance,
an HIV particle that's resistant
to one of the antiretroviral drugs,
chances are it wouldn't be resistant
to the other two drugs that make up that
particular HAART cocktail.
And you know it would be really hard
for HIV to become resistant
to all of the drugs in a particular HAART regimen.
I mean, here, let's do some math.
Not super hard math,
I'll leave that to Sal,
but in your body HIV multiplies essentially,
and it creates a few billion new viral particles per day.
And during replication,
it's reverse transcriptive enzymes
makes a lot of mistakes,
in fact, for every about 10,000 nucleotides
it adds on to a new strand of DNA
it makes a mistake,
and it inserts the wrong base.
One in every 10,000 bases is wrong.
And it doesn't have a very good repair mechanism
like we do for our DNA,
so this mistake sticks around.
So let's say, for arguments sake,
that one of these mistakes affects one of our
drugs target proteins within the HIV.
Let's say this stretch of DNA here
was supposed to code for intergrace.
So this virus's intergrace enzyme
will still work,
but our intergrace inhibitors
might not be able to stop it anymore
because it's mutated.
Well, our HAART cocktail
would still be able to stop this mutant HIV
because we have other places in the replication cycle
that we can inhibit it.
So essentially, a virus would have to mutate,
either randomly, or sort of evolve
by selective pressure
to become resistant to all of
the HAART drugs that we're throwing at it
in a given cocktail.
And, in fact, the chance that it could become resistant
to all three of the types of drugs
would be at the very least
one in ten to the twelfth power,
that's one in a trillion chance.
I'm just multiplying one in 10,000 here
by one in 10,000 here,
by one in 10,000 here.
And, you know, I'm being really generous here,
because this is assuming that
the one in 10,000 base mutations
are even occuring at the target enzymes
coding sequence of DNA.
So, bottom line here
is that it will be extremely unlikely
for an HIV particle to mutate
during replication in a way that would let it
escape from all three of the HAART drugs.
And you know, of course, it would be
extremely unlikely to thus find an HIV particle
just floating around in the bloodstream
that's resistant to multiple drugs.
Because remember, replication is actually suppressed
by taking the ARV,
so once you're on HAART,
potential mutants aren't even being created anymore.
Or, at least a lot less so.
So now you have an idea
of what HAART is,
a drug cocktail,
two to three different types of drugs
all taken together that
A. Makes drug resistance by HIV really unlikely,
and, B. That's still able to fight off
resistance strains that we might encounter.
But you know, there's a few other things to consider
I mean, for example, who gets HAART?
And when is it prescribed
during the course of the infection?
And, how do you sort of take it?
I mean, is it a bunch of pills?
Is it an injection?
Well, let's start here
with who and when.
Because you might reasonably think
that, you know, everyone who's diagnosed with HIV
gets started on HAART right away
and you know there's good evidence
that that is a good idea.
But it gets a little complex
because there are some drawbacks
to starting therapy early
and by early, I just mean before the onset of any symptoms
or AIDS defining illnesses, and,
you know, these drawbacks need to be considered.
For example, there are some side effects
of the ARV drugs,
such as an increased risk of cardiovascular disesases
like heart attacks, or strokes.
There's potential problems with bone health too,
long term exposure to these ARVs are
associated with a greater loss of bone density
as a person gets older.
More than the normal loss that happens as you age.
There can be psychiatric side effects, too,
like feeling a bit sort of sluggish in your thinking.
And there can be gastroinestinal side effects, too,
like chronic diarrhea.
So you can imagine that if someone has HIV
but they're in the latent phase,
in other words they're not having any symptoms,
starting them on antiretrovirals
might actually cause a decrease
in their quality of life
at that given time period.
The other thing that needs consideration
is that, you know, if you do start a HAART
treatment regimen then you need to stick to it
for the rest of your life,
taking your medication
every single day without fail.
Because studies have repeatedly shown
that stopping your ARVs,
or not taking them every single day
is associated with the HIV in your body
becoming drug resistant.
So that means that in the future
if you decide to start your treatment again,
your drugs just may not work as well anymore.
They may not work at all, anymore.
So when you talk to your doctor
about the right time to start your treatment
you'll probably go over some strategies
to make sure you can take your medication
every single day
to minimize drug resistance
from happening in your infection.
And one thing that's helped out in a huge way
for people taking their medication every day,
is the fact that these combinations of these drugs,
remember, you're taking cocktails of usually
three of these types,
combinations are available in a single daily pill,
nowadays, and that makes it a lot
easier to stick to your treatment schedule.
I mean, a few years ago,
and actually still in some countries,
you'd have to take a handful of pills
every single day,
sometimes multiple times a day.
And now you can get your whole combo
in one single pill, taken once a day,
so that's really, really useful.
So now we know there's potential problems
with starting HAART too early.
But you know, when is the right time to start, then?
Well, it is a little different for each person,
so you'll have to have a chat with your doctor
about the right time to start,
but there's a few general principles
that'll help guide the decision
that you guys come to.
So for one, we know that if your CD4 T cell count
is less than about 350 to 500 cells
per cubic millimeter of blood
then it's time to start HAART.
Remember, CD4 count is sort of used as a marker
for how far along the illness is, right?
The lower the CD4 count
the more damaged the immune system is.
Viral load is important too.
If the amount of HIV in your bloodstream
is higher than 100,000 copies per millimeter of blood,
it's time to start HAART.
And, I know, the last thing I'll say about this is
is if a person is pregnant,
if they're a young child,
if they progress to AIDS,
of, it there's an opportunistic infection
or an AIDS defining illnesss present,
then regardless of CD4 count,
even if you're higher than that 350 to 500 cutoff,
HAART needs to be started right away
to hep your immune system recover
as much as possible.