A biologia básica do vírus HIV e da doença que ele causa, a Aids. Os fatores econômicos, sociais e políticos que determinam quem adoece e quem permanece saudável, quem vive e quem morre . O progresso da pesquisa científica e dos tratamentos médicos. Razões para esperança; razões para o medo. (Para ver alguns dos materiais que os alunos postaram no fórum do curso, vá para @AIDSFAH ou #AIDSFAH)
07.03 - The Search for a Cure
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Do curso por University of Michigan
AIDS: medo e esperança
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Unit 7 - Wrapping Up
Cure? Legal Issues, Cost, The Future, Acting Up
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Richard Meisler, Ph.D.Lecturer
Department of American Culture, University of Michigan
We do not have a cure for HIV.
Antiretroviral therapy keeps an HIV infection at bay.
Patients remain healthy and can live long lives, but
they must take their medicine everyday, and if they fail to do so,
the HIV infection will return and make them sick.
Antiretroviral therapy costs thousands of dollars per patient.
In this session, we look at part of my conversation with Dr. James Riddle,
and he explains the difficulty of finding a cure for HIV infection.
He goes on to describe the lines of pure research that are being explored.
Dr. Riddle describes the main barrier to ridding the body of HIV.
The virus hides in several reservoir sites in the body,
lying dormant, but always having the possibility of becoming active again
if a patient treated with antiretrovirals goes off his or her medication.
Dr. Riddle himself participates in research
looking into the details of HIV hiding in reservoir sites.
At one point, as he describes HIV in the central nervous system,
he refers to CSF, which stands for cerebral spinal fluid,
the fluid that doctors look at when they do a spinal tap.
When Dr. Riddle talks about the Berlin patient, the only person we know
to have been cured of an HIV infection, he mentions the CCR5 receptor,
which is a chemical on the surface of white blood cells.
The CCR5 receptor is used by HIV to enter and infect the cells.
He then mentions the Delta32 mutation,
a genetic mutation that changes the CCR5 receptor.
The changed CCR5 receptor cannot be used by HIV to infect cells.
Someone with that mutation, then, is immune to HIV infection.
Dr. Riddle explains how the Berlin patient benefit, benefited from all of this.
Dr. Riddle then talks about the Mississippi baby,
another patient who seemed to have been cured of an HIV infection.
I recorded my conversation with Dr. Riddle on July 2nd, 2014.
Only eight days later, on July 10th,
researchers announced that the Mississippi baby's HIV infection had returned.
And so the baby was not really cured.
This was a great disappointment, of course.
When I teach about HIV and AIDS, I always stress how quickly the field is changing.
This is an example.
I decided not to omit Dr. Riddle's discussion of the Mississippi baby
from this video session for two reasons.
The first is that I wanted to,
you to know about the baby's case, even though the outcome was discouraging.
Also, I'm using it to underline the other fact, how quickly things change.
One goal I have in this course is to give you enough background knowledge
to follow such changes in the news as they occ, occur.
And things are moving rapidly.
Here again is Dr. Riddle.
We don't have a cure for HI, for
HIV infection because the virus hides and can't be reached by drugs.
>> Correct. With our current technology.
>> With our current technology.
So let's talk about the search for cures, the search to try to overcome this.
>> Right. So that's been really exciting.
So I'll refer to the Berlin patient where sort of this idea sort of first started.
This is a patient who had hematological malignancy and
needed a bone marrow transplant.
>> Was it lymphoma?
>> I believe it was a leukemia.
>> Leukemia, yes.
>> And and it turned out that he had a very common haplotype, so he had multiple
donors that could donate bone marrow to him for his bone marrow transplant.
And so what they're able to do is go through each of these donors and look for
one that had the Delta32 mutation and the CCR5 co-receptor.
So CCR5 is required for HIV entry to T cells.
>> We'll explain that in a minute, okay?
>> Okay.
>> But the donor had that-
>> The donor had this mutation.
>> A mutation. >> A mutation, right.
So they gave the patient, so they gave, they era, they eliminated the patient's
immune system with chemotherapy, and then they rescued him by giving
the donor's bone marrow basically, and then that takes hold.
And then once those cells mature and form a new immune system,
this new immune system then is resistant to HIV entry into T cells.
>> Just to sort of repeat it.
The donor who had this mutation himself was
immune from HIV infection.
He, he was one of a very small group of people who have this mutation, and
the mutation protects him.
>> That's, that's correct.
>> And so now that the Berlin patient received this bone marrow transplant
with the same mutation, he was also successfully protected.
>> That's correct.
>> From HIV, even though he had previously been infected.
>> That's right, that's right.
>> So that was extremely exciting.
>> That's pretty exciting.
>> But with a very special circumstance.
>> That's right, that's right, and
now we have several years of followup on this particular individual, and
he still has not exhibited any evidence of viral replication, even off HIV medicine.
So it seems like a strategy that, that works.
>> And to be, to be clear, bone marrow transplant is so
difficult and so expensive.
And, and that it doesn't itself, doesn't represent a cure for that.
>> [LAUGH] >> Except in very special cases.
>> That's right.
>> Yeah. >> It's a very specialized circumstance.
It's such a, a traumatic [LAUGH] and-
>> Right. >> Expensive and
costly difficult process to go through.
It's not something that, that's commonly used for sure-
>> But it's exciting because there was some one cured.
>> Exactly. Right, and
so now we sort of have a proof of principle that this can be done, and so
can we look at this strategy and try to extrapolate to other situations.
So, another way that people have tried to use this information
is to take your own immune cells,
take them out of your body infect them with a virus that then mutates.
This is a gene therapy approach,
that would then mutate your receptors in your cells and then give them back to you.
And that approach has been tried, but
the problem there is that the cells are short-lived.
And so it's not sort of lasting type of treatment.
But people are working on other strategies-
>> [CROSSTALK] But the goal would be to get at least some cells into
your body with that mutation.
>> That's right.
>> And try to do it in such a way that those cells
duplicated themselves, replicated themselves.
And you had a population of CD4 cells that would not be susceptible to HIV.
>> That's right.
That's right.
Yep.
But to do that you'd have to again, use chemotherapy to do what they call
an autologous stem cell transplant, to make those cells continue to replicate.
So that's, that's the trick, is that we haven't quite figured out a way to do
that without significant intervention, which could not really be commonly used.
>> And tell us about the famous baby in Mississippi.
>> Right. So that's another interesting case for us.
This is a infant where the mother came in to deliver,
and it was not known that she had HIV infection at the time, but then it was
then discovered around the time of delivery that the mother was HIV infected.
And it was, viremic, and when the baby was born, rather than doing sort of,
what would be considered the standard post exposure prophylaxis,
a full antiretroviral regime was administered, three drugs, three
active drugs as opposed to two, which would, had been the standard at the time.
And by-
>> So this baby is at such high risk.
>> Very high risk. >> That we're going to clobber that HIV
immediately with three drugs.
>> That's right. That's right.
And the baby initially had viremia, was detected.
So presumed to be infected.
And the, this was measured over time, and
it was found that with treatment the viral load decreased.
But then the baby was lost to follow-up for a period of time.
And had, the mom had actually stopped giving the baby medication.
And then when they came back for follow-up, they tested the baby and
did not find HIV.
And they tested multiple, the baby in multiple different ways,
looking for HIV in different cell compartments and different types.
And we're really not able to find it except integrated into resting T cells.
So no active viral replication at all.
So this was considered just sort of be a, a cure [LAUGH] of the symptoms.
>> How's that baby doing, do we know?
>> And the follow-up on that is that the baby is still doing fine.
And It's not had recurrent pyaemia, and this is now going on two years or so.
>> Mm.
>> I think I believe the reports of other infants that are similar and
have been in a similar situation where the same strategy's been tried.
>> I know I'm asking you to speculate but so
we have a couple of rare, unusual cases.
But we didn't have those before, just a, a few years ago.
In the early days of my course when you came to talk about HIV and AIDS,
we never talked about a cure, but now we're talking about it.
>> That's right.
>> So, speculate for us.
Do you think that these lines of research and development are promising?
Do you think we're going to find a cure?
>> I think it's promising, I think we have a ways to go.
And I think, right now we're in the stage of
it's just sort of having the concept that a cure is even possible, and you're right.
Just, you know, three or four years ago that wasn't even
really on the radar screen, but now that we've seen some of these cases
we're starting to understand more about the basic biology and reservoir sites.
I, I think we're starting to get to the point where we can think about that in a,
in a more comprehensive way.
I think the first steps are going to be to really understand reservoir sites.
>> Which is what you're working at.
>> Which is what we're working on.
And then the next step after we understand reservoir sites is how do we get the virus
that's in those reservoir sites to become active so that antiretroviral therapy or
the immune system can then eliminate the virus from those sites.
And once we understand how to eliminate the virus from those sites,
then we'll be on the track to some sort of a more curative, or
at least maintenance type of situation.
That also leads into our approach, now, for antiretroviral therapy
with initial infection, we were talking about acute infection earlier.
We know that if you start treatment right away,
at the very early stages of infection in an adult, now not necessarily an infant,
you can reduce the amount of reservoir sites that then become infected.
>> Really, I didn't know that.
>> Thus, making it easier long term to manage the, the virus.
>> So that's another reason for treating as soon as you can
the problem of hidden HIV is reduced.
Is that correct? >> That's right.
Yeah, that's right.
And so the earlier you diagnose and treat the better off they are,
especially if it's in that acute infection stage.
>> Mm-hm.
Acute infection is the first few weeks really.
>> Within the first few weeks.
>> Yeah.
>> You know, be before some of the reservoir sites can be fully
populated is the idea.
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