Let’s look at the clinical
course of HIV disease.
If you look at the yellow line first of all,
this is the amount of
viremia, measured by the amount of HIV RNA that’s present.
As you can see, following the initial infection,
the amount of virus RNA rapidly increases.
If you look at the blue line, which is the number of
CD4 T-cells present, you can see that they decline.
At this point, following primary infection,
there is the acute HIV syndrome with
wide dissemination of virus, and a seeding
of lymphoid organs with the virus.
However, within a small number of weeks,
it seems like things are going well.
The number of CD4 T-cells begins to
increase, and the amount of virus decreases.
However the virus is not being eliminated,
it is entering a period of clinical latency.
Then after a very variable period of time, which may be
a short number of years or maybe many, many years later.
The individual will begin to develop
constitutional symptoms, there will
be opportunistic infections, and
opportunistic tumors that begin to arise.
And the amount of virus
begins to increase.
And the number of CD4+ T-cells
begins a rapid decline.
The patient then has the Acquired Immune
Deficiency Syndrome, and without medical
intervention, death would be more or less
inevitable in the vast majority of individuals.
Fortunately, the use of antiretroviral drugs
can prevent this process leading to death.
Here we see the amount of antibody and cytotoxic T-cells
being produced, and the virus particles in the plasma.
So again, looking initially at the yellow line,
you can see that the virus goes up following
an initial infection and then radically goes
down, looking at virus particles in the plasma.
You’ll see that it looks like a good
immune response is being developed.
In the blue line, you can see that cytotoxic
T-lymphocytes specific for HIV is being produced.
response is being produced.
You can see that there are
antibodies against envelope proteins.
Gp120 being produced;
the red line there.
And the green line you can see that there are
antibodies against p24, another component of the virus.
So everything looks to be good, the immune response
is kicking off and the virus is going down.
But then over time, the immune response will decline
and particularly the virus particles will come back up.
And the most crucial decline here as we saw on the
previous slide, is the decline in CD4+ T-cells.
So what are the major hurdles to
elimination of HIV infection?
Well there are long term reservoirs
of HIV that are established, which
include the HIV being latent within
macrophages and within memory T-cells.
The extremely high mutation rate of
HIV leads to an evasion of the host
immune responses, and to resistance
to anti-retroviral drug therapy.
The clinical features of HIV infection depend
upon the particular stage of the disease.
So during the acute phase, there is a fever, a headache, sore
throat; really symptoms that are
very similar to a flu-like illness.
During clinical latency, there is a
declining blood CD4+ T-cell count.
And then when the disease progresses to become
the acquired immune deficiency syndrome,
there is a whole range of opportunistic
infections that the hosts become troubled with.
And these range across the whole spectrum of different
types of pathogen - protozoa, bacteria, fungi, viruses.
And you can see some of the more
important ones listed there.
In addition to being more prone to opportunistic infection,
there is a increased instance of certain tumors.
So lymphomas, including Epstein-Barr virus-associated
B-cell lymphomas, Kaposi’s sarcoma and cervical carcinoma.
There is also encephalopathy, wasting syndrome, HIV associated nephropathy and immune reconstitution inflammatory syndrome.
So how do we treat HIV infection?
Well the mainstay of treatment
is anti-retroviral therapy.
And there are a number of anti-retroviral
drugs that have been developed.
These include the non-nucleoside reverse transcriptase
inhibitors, the nucleoside reverse transcriptase inhibitors, the
protease inhibitors, fusion inhibitors, entry inhibitors such
as CCR5 antagonists, integrase strand transfer inhibitors.
And a combination of drugs being used as
highly active anti-retroviral therapy,
which comprises three of more drugs
from at least two different classes.
There is also the possibility
of treating HIV post-exposure.
Obviously preventative measures are best, but
immediately following exposure, commencing
within 72 hours of exposure, there are drugs--
anti-retroviral drugs that can be given.
These must be taken for 28
days following exposure to HIV.
And again, a combination of two or three
anti-retroviral drugs is employed.