So, what are those opportunistic
And those are called, variably,
AIDS-defining infections, or in this case,
AIDS indicator diseases,
and they are many.
And they correlate with how
immunosuppressed the patient is from
the attack on the CD4 count.
We'll start with bacterial infection,
and these can be
bacterial infections which normally
virulence, limited pathogenicity.
For example, a nontuberculous
or an atypical
This is known frequently as MAI or
MAC -- Mycobacterium Avium Complex.
Normally, this causes only rare disease
occasionally in children causing
chronic lymph nodes.
But in patients with HIV, it can cause
disseminated disease causing
lung disease, pneumonia, enteric disease
enteric lymph nodes.
And it is typically seen when the patient
is very immunosuppressed.
Their CD4 count, not percentage,
but number of CD4 cells per
milliliter of < 50.
Similarly, these patients can develop
Tuberculosis, extra pulmonary
They develop pneumococcal sepsis,
name the bacteria, and they can develop
overwhelming disease from any of those.
Viral infections especially are known
to be cytomegalovirus
and chronic or disseminated herpes
So, too, as immune discovery wanes,
they can be at risk for escalation
or activation of JC
virus causing progressive multi-focal
Fungal infections, anything and
So, candidiasis, a very simple yeast.
Candida which exists everywhere causes
thrush in children who are nursing
a slightly infected breast.
The candidiasis can be overwhelming,
and it goes
not just from the mouth, it's
not just thrush
in a patient with HIV, but it travels
all the way
down through the GI collecting system.
Not just the esophagus,
but including even
intestine to where it can
There can be pulmonary candidiasis.
There can be anything and everything.
Cryptococcal meningitis, that's
a classic one.
Cryptococcus is an environmental
in most immunocompetent people
doesn't do anything because we
enough immune discovery to limit that,
and it's typically addressed
But in an HIV patient with a CD4
count < 200,
the ability to stimulate macrophages by
interferon -- alpha and interferon gamma
is limited, as we just talked about.
Thus these patients are at risk for
Similarly, histoplasmosis, another
which used to be known as pneumocystis
carinii, PCP. It's now PJP.
It is also unclear if it's a bacteria
or a fungus, but it causes a diffuse
All these are seen in patients who are
starting to lose their CD4 count.
Protozoal infections such as
cerebral toxoplasmosis as the patient
gets to a CD4 count < 100.
And then they also can, develop
due to lack of
immune -- actually increased,
I'm sorry -- immunotolerance, lack
of immune discovery,
they can develop cancers because
the proliferating cells don't have
due to an absence of natural
killer cell function,
CD8 cellular or cytotoxic function.
And then, unrelated necessarily to the
but still certainly quite common is HIV
And there is a massive weight of research,
pardon the pun,
which has been aimed at trying
why patients with progressive
lose so much weight.
And it's not just fat, but it's fat,
muscle, you name it.
So, how do we diagnose HIV infection?
Well, there are many
screening tests including fourth
generation screening tests,
basically all looking for evidence of
specific antigens to HIV.
And those are enough to at least get
that first screening positive,
but they need to be confirmed either by
Western blot or far more commonly now,
Western blot is able to detect
antigens or even proteins specifically
expressed by HIV,
including the envelope proteins and some
others, the specific ones
that we've mentioned are produced by HIV.
However, once the diagnosis is made,
or to confirm the diagnosis,
use of a reverse transcriptase PCR
to give a quantitative
estimate of how many RNA copies exist
in the bloodstream is absolutely how
we follow these patients.
So, too, we'll look at the number
and the percentage of
CD4-positive T lymphocytes in the
Here's an important factor for
Patients may have a low CD4 number
if their total number of circulating
white blood cells
is low as well.
It kind of makes sense.
So it's far more sensitive look
at the percentage
of the lymphocytes which are CD4-positive
or the percentage which are not
When the percentage drops below 15%,
15%, that is when one is in trouble and
can expect to have a specific
targeting action on the CD4-positive
Another way which is also
is to look at the ratio between CD4-positive
positive T lymphocytes.
Normally, in healthy individuals,
that ratio is 2 -- 2:1.
In somebody with active HIV
infection or active
retroviral attack on the CD4 cell,
that ratio typically drops to 0.5 --
It's a significant difference and
it's quite sensitive.
Treatment, historically, was initiated only
when the patient developed
AIDS-defining illnesses or opportunistic
due to a wealth of research,
it's far more expedient, far
to start treatment as soon as the
diagnosis is made.
So, at the very least, we will
with the patient, you know, strongly
advise them to start treatment
when their CD4 count drops below 500,
which is the indication of first trouble.
And you see here
that one can start with AZT, a reverse
in combination with lamivudine or a non-
nucleoside reverse transcriptase inhibitor.
Those are 2 possible ways to
from an infected mother to the baby.
However, those 2 drugs by
themselves will not
be sufficient to treat HIV anymore.
Although, historically, we started
with just that;
AZT and another NRTI -- nucleoside reverse
Instead, now, we start with
highly active antiretroviral therapy,
which can be several of the
different types of
retroviral medications in combination,
typically including 1-2
protease inhibitors, and
1-2 nucleotide or non-nucleotide reverse
in combination, many times,
with integrase or sometimes some other
So, the ideal combination
remains to be completely described, but
there are many which are exactly perfect.
That is what we know.
There's actually a lot more, but not
time in this session
to talk about for HIV infection.
But let's look briefly at human
T lymphotropic virus type 1, or
HTLV type 1.
The primary target, just as it
was for HIV,
is the CD4 T lymphocyte and secondarily,
neurons when they become inflamed.
This virus also carries a protein
which can upregulate both interleukin-2
production and interleukin-2 receptors,
which is a way to further stimulate
the CD4 T lymphocyte
So, it increases and actually in an
proliferation of the T lymphocytes.
Those proliferating T
lymphocytes then develop chromosomal
normal mutations occur, unfortunately,
quite frequently in human body.
And when one gets the proper
chromosomal aberrations, those cells
So we are talking a pre-malignant virus
by doing its targeting action on CD4 cells
and then upregulating their function.
So, adult T cell
leukemia/lymphoma which is a direct
result of this process
will generate cells such as you see in
front of you, which looks
as a flower or a violet, as has
And it's a circulating malignant cell, which
can be found anywhere:
bone lesions, lymph nodes,
in the skin, etc., and is typically associated
as a sign of increased cell turnover,
Acutely, this illness is lethal
within 1 year,
as would be many other hematologic
malignancies without intervention.
Even in chronic form,
it's similar to a non-Hodgkin lymphoma,
a long array of chemotherapy
agents and support.
So, this is a very concerning section.
The retroviruses have significant
and mortality associated with them
because they target a critical part of
human immune architecture
And they do so in a very difficult,
challenging, hard-to-treat way.
So, look for more information on
this subject coming.
We have a long ways to go to try and end
the intervention or end the impact
of the retroviruses.