

HIV returns in two patients after bone marrow transplant - linux_devil
http://edition.cnn.com/2013/12/07/health/hiv-patients/index.html

======
carbocation
This isn't all that surprising given that they did not receive special bone
marrow, but it is very sad for these patients.

<speculation>Even in the Berlin patient, it is likely that there is some
reservoir of HIV+ cells, but because his transplanted bone marrow lacks the
CCR5 receptor, that reservoir cannot expand, so he appears cured (and, for all
purposes, is).</speculation>

~~~
dnautics
well then it seems the faulty assumption is that the HIV virus in his body
only can attach to the CCR5 receptor, when what is likely is that some nonzero
pool of virus has mutated to attach to another receptor altogether or have
slightly less affinity to CCR5 but a hybrid affinity with another receptor.

These virii will then have the capability of hiding in a different cell type
from immune cells, and come back later.

~~~
carbocation
I think there is some confusion. The Berlin patient, the one who was
transplanted with CCR5-negative donor stem cells, is still cured. Therefore,
none of that explanation is needed.

~~~
dnautics
thanks carbocation. Strangely enough, I remember you from the chembark days.
You should check out what I'm doing (see profile).

~~~
carbocation
Awesome; I see
[http://www.indysci.org/projectmarilyn/](http://www.indysci.org/projectmarilyn/)
from your profile. Looks like your fundraising starts tomorrow? I hope
everything goes well. What you're embarking on has probably not been tried
before and will be very interesting, so please keep us posted.

------
wfunction
> "If you have an underlying neoplasm (tumor) like these patients had, then
> the risk outweighs the benefit," he said. "However, if you are doing well on
> ARVs and you merely want to get off antiretroviral therapy, then the risk
> seems greater than the benefit."

Is this a typo or am I misreading it?

~~~
carbocation
It's a typo or a misstatement. He meant to say that if you have cancer and
HIV, then the benefits of BMT outweigh the risks (purely due to cancer).

If you have just HIV, then the risks of BMT outweigh the benefits (because of
high near-term mortality).

------
chimeracoder
This is very disappointing to see.

I often see people wondering why HIV has evaded both a vaccine and cure for so
long, despite the amount of attention and money it has received.

The HIV virus is remarkably fragile and (relatively) difficult to transmit.
However, it mutates incredibly quickly compared to other viruses - an HIV+
patient may have multiple strains of the virus in their body at any one time,
requiring the infamous "cocktail" of drugs as no single drug will be
effective.

Vaccinations have been (so far) ineffective because they attempt to vaccinate
against a rapidly moving target.

Hepatitis B, on the other hand, is a much more easily-transmitted virus, and
yet we have been able to develop a reasonably effective vaccine against it[0].
For a while, it used to be standard practice to vaccinate all young children
against Hepatitis B; I'm not sure if it still is.

Unfortunately, Hepatitis C, which kills more people in the US than
HIV/AIDS[1], is arguably even worse - it is also much easier to transmit than
HIV, but we don't have a vaccine against it either. Furthermore, because most
of the public campaigns advocating safe sex and clean needles use HIV-specific
language, many people aren't aware that it is such a huge threat. Like HIV, it
is asymptomatic for several years, so as many as _75%_ of people infected with
Hepatitis C don't even know it[2]:

Epidemiologically (not politically) Hepatitis C today is similar to the state
of HIV in the 80s and 90s[3]. We have some medications to treat it, but
they're not very effective - living with Hepatitis C is oftentimes _worse_
than living with HIV.

[0] As with all vaccines, it is imperfect, which is why coverage across the
general population is the best approach to eradication or containment.

[1]
[https://en.wikipedia.org/wiki/Hepatitis_C#Epidemiology](https://en.wikipedia.org/wiki/Hepatitis_C#Epidemiology).

[2]
[http://m.cdc.gov/en/VitalSigns/hepatitis-c](http://m.cdc.gov/en/VitalSigns/hepatitis-c)

[3] At least outside the US - the US was one of the last countries to approve
HIV antiretrovirals, which incidentally is the topic of a movie currently in
theatres:
[https://en.wikipedia.org/wiki/Dallas_Buyers_Club](https://en.wikipedia.org/wiki/Dallas_Buyers_Club)

~~~
toufka
> an HIV+ patient may have multiple strains of the virus in their body at any
> one time

It's even crazier - an infected person has enough virus, and it mutates
readily enough, that somewhere in their body is a single viral particle with
each single point mutation variant. Every variant is in every person.

Another important point is that its latent phase is just so dormant - and for
so long (relative to other viruses). We have pretty effective drugs to kill
those viruses that are not latent. But there are always survivors. In fact
there are a number of therapies that do nothing but try to _force_ the virus
to become active, so that the other therapies can (reliably) kill it. And even
then, there's some that stay latent ready to stochastically turn on at some
point.

~~~
waps
This is because HIV is a brilliantly designed virus (of course it evolved,
it's not designed. I don't know a better way to say this though). It's a
third-generation retrovirus, meaning it defeats internal cell safeguards in a
very clever way, meaning that if one cell of a few types comes into contact
with ~10 virus particles, you effectively have AIDS. For the flu we're talking
hundreds of cells needing to be in contact with thousands of virus particles.

It evades being a target for vaccination by using internal body networks to
transmit itself as opposed to the blood. The immune system inside our bodies
has a sort of chemical protocol for one cell to exchange data with another.
One cell approaches another, presents a specific molecule, and the cells link,
exchange something (we don't know what, or why, or how for that matter), and
the HIV virus slips along.

This means HIV looks at the immune system from behind all the detection
mechanisms. You can look at immune cells as a mine : they have lots of traps
on the outside. Trigger one of them and a massive army of huge, very angry,
and very dangerous cells will overwhelm whatever triggered it
([http://www.youtube.com/watch?v=JnlULOjUhSQ](http://www.youtube.com/watch?v=JnlULOjUhSQ)
_), and a large part of things nearby that didn 't trigger it too, usually. So
where does HIV hide ? Simple : on the inside of the mine, transmitting itself
to other mines when through the mechanic that comes by to repair the mine and
doublecheck things every now and then.

There's other virii doing this, however they don't generally hide in the
immune system. But for example Bof has the same tactic. It hides on the inside
of cells, then every 3-4 months or so, one of the virus particles suddenly
starts multiplying and makes it's host cell explode. The virus particles
immediately get slaughtered by the immune system, but not before spreading the
infection.

HIV is also mutating on purpose. Part of it's DNA (yes, the virus itself has
RNA, however it's a direct analog. The virus, when in operation, consists of
DNA though) is dedicated to mutate. It's got a long list of mutation
instructions targeting specific parts of it's DNA, generally the ones
referring to the virus mantle, but there are others. Effectively it contains
instructions to copy it's RNA, then change the values at position x,y,z by
random values from a specific range.

And HIV generally gets things right. It doesn't ever multiply fast enough to
really set of alarm bells in the immune system. It avoids entering the blood
stream except to spread from one human to the next(which is why even with
regular sexual contact with an HIV positive individual, it takes ~6 months to
get infected), and waits just long enough for the immune system to calm down
before trying it again. It does this while still spreading fast enough to very
slowly increase the number of infected people.

There are a number of countries on this planet, mostly in Africa and the
middle east, where HIV has gone from being endemic to worse than that. In
several places it is a matter of time until 100% of the population will be
infected.

It is a very, very interesting virus.

A piece of good news is that, over time (but quite fast given that this is
evolution we're talking about), HIV is becoming less lethal. This is exactly
because it's infecting a significant fraction of living humans (without
killing them). HIV is hardly the first virus to infect 100% of the human
population, and there are some indications that other such viruses were
somewhat similar. It also means that the evolutionary selection criteria for
HIV will match those of the human race before long, and it should at some
point mutate into a beneficial influence on the human race. The only way for
HIV to spread it's genes will soon be to make more humans. At that point, it's
no longer a virus but a part of humans, not much different from say, your
liver, and it will find some function to fulfill. And again, it's hardly the
first time this is happening to the human race, and it won't be the last.

_ yes this is not actually showing the cell type HIV attacks. However as far
as I know there is no known video of the correct cell type actually doing
something. Plus it's a very cool video.

------
maho
This article contains more information while (thankfully) being significantly
shorter:

[http://www.iasociety.org/Default.aspx?pageId=5&elementId=156...](http://www.iasociety.org/Default.aspx?pageId=5&elementId=15623)

It highlights what the difference between the treatment of the Berlin patient
and the treatment of the two Boston patients was.

------
yason
Maybe it isn't entirely a physical disease.

~~~
possibilistic
Every disease has a physical, etiological agent.

