Вич.ppt

HIV
Human Immunodeficiency Virus

Table of contents
 What is HIV?
 What is the difference between
HIV & AIDS?
 What are Opportunistic
Infections?
 Myths and Misperceptions
about HIV
 HIV Transmission
 Understanding the Immune
System
 Understanding Lab Tests
 Diagnostic Tests
 Understanding CD4 and CD8
Cells
 Immune Reconstitution
 Considering HIV Treatment
 Starting Treatment
 Adherence
 Drug Interactions
 Side Effects
 Resistance
 Pharmacokinetics (PK)
 AIDS Vaccines
 RIGHTS
 Thank You

What is HIV?
 HIV stands for Human Immunodeficiency Virus. HIV is
the virus that causes AIDS (Acquired Immune Deficiency
Syndrome). AIDS is the most advanced stage of HIV
infection.
 Many Viruses can be controlled by the immune system,
However HIV targets and infects the same cells that
would otherwise protect us from illness. These are a
type of white blood cell called CD4 cells.
 HIV takes over CD4 Cells and turns them into virus factories that
can produce thousands of viral copies.
 As the virus grows, it damages and kills CD4 cells, thus
weakening the immune system.

What is HIV?
 Please use the following Youtube link for a video
on HIV. It is a good insight to how the virus
actually works in the body. Some terms may be
difficult, however with the information gathered
throughout this presentation, perhaps come
back and have another look at the end. Some of
the terms used will then seem more familiar.
 Targeting HIV Replication

What is the difference between HIV
and AIDS?

What is the difference between HIV
and AIDS?
 You do not have AIDS upon infection of HIV
 You can be HIV positive for years with no signs of disease, or only
mild to moderate symptoms.
 Without treatment, HIV will eventually wear down the immune system
in most people to the point where they develop more serious
Opportunistic Infections (OI’s)
 The Centres for Disease Control and Prevention (CDC)
defines someone as having AIDS if he or she is HIV positive
and meets one or both of these conditions:
 Has at least one of 21 AIDS-defining Opportunistic Infections
 Has a CD4 count (T cell) of 200 or under (a ‘normal’ CD4 count is
usually in the 600-1’500 range).

What are Opportunistic Infections?

 While many viruses can be controlled
by the immune system, HIV targets
and infects the same immune system
cells that are supposed to protect us
from illnesses. These are a type of
white blood cell called CD4 cells. HIV
takes over CD4 cells and turns them
into virus factories that produce
thousands of viral copies. As the virus
grows, it damages or kills CD4 cells,
weakening the immune system.
 When the immune system loses too
many CD4 cells, you are less able to
fight off infection and can develop
serious illnesses, cancers, and
neurological problems. These are
called opportunistic infections (OIs)
because they take advantage of the
body's weakened defences. OIs can
lead to hospitalization and disability,
and are responsible for most of the
deaths in people with AIDS.
 The Centres for Disease Control and
Prevention (CDC) defines an HIV
positive person with a CD4 cell count
of 200 or less as having AIDS. The
CDC has also developed a list of more
than 20 opportunistic infections that
are considered AIDS-defining
conditions. If you have HIV and one or
more of these OIs, you have AIDS.
 Even if your CD4 cell count goes back
above 200 or an OI is successfully
treated, you will still have a diagnosis
of AIDS. This does not necessarily
mean you are sick or will get sick in
the future. It is just the system used
by the government to count the
number of people who have been
diagnosed with AIDS.
Basic Facts

 The best way to prevent OIs is to
keep your immune system as
strong as possible by taking HIV
drugs before your CD4 cell count
falls too low (below 200). This
allows the immune system to do
its job of controlling infections.
 If your CD4 cells do fall below
200, taking appropriate
medication at certain CD4 cell
levels can prevent many OIs from
developing. Taking medication to
prevent disease is called
“prophylaxis.”
 Effective treatment options are
available in most cases if you do
develop an OI. After you recover,
you may still need to receive on-
going maintenance treatment to
prevent the OI from coming back.
 You may be able to stop
prophylaxis or maintenance
treatments if your CD4 cell count
goes up. You should not
discontinue any treatment without
discussing it first with your doctor.
Preventing and Treating OIs

 The following slides
supply information on
the most common OIs
in HIV positive
people.

What are Opportunistic
Infections?

Myths and Misperceptions about
HIV

HIV
 Many of the stories and rumours surrounding
HIV are exaggerated or just made up. When
dealing with HIV, it’s important to know reality
from myth.
 Believing myths can results in denial, fear and
a change to your health
 The following pages will demonstrate some myths
and the reality surrounding HIV

HIV
Myth:
“HIV doesn’t cause AIDS”
Reality:
 If you don’t have HIV, you
cannot get AIDS. If you have
AIDS, you have HIV.
 20 years of scientific proof
have verified this.
 AIDS is not caused by party
drugs, government
conspiracies or anything else
but a virus

HIV
Myth:
“It’s not the AIDS that kills
people, it’s the medication
they take”
Reality:
 HIV medications, known as
antiretrovirals don’t cure HIV,
but they can keep people
healthy for many years. People
died from AIDS before
antiretrovirals became
available.
 Unfortunately the drugs do
have some side effects and
toxicity (for some people), that
can be life threatening

HIV
Myth:
“The ‘AIDS test’ can’t be
trusted”
Reality:
 Viral Load tests measure
the amount of HIV in a
person’s blood. Studies
have proven that people
with a high viral load are
much more likely to
become ill or die than
those with a low viral
load.

HIV
Myth:
“Viral load tests don’t really tell us
anything about a person’s
health”
Reality:
 The ‘AIDS test’ measures your
body’s response to HIV, called
antibodies. The HIV test is one
of the most reliable medical
tests. According to the Centres
for Disease Control and
Prevention, it is more then
99% accurate. In addition, all
positive tests are confirmed
with another test to ensure no
mistakes are made.

HIV
Myth:
“Straight people don’t get
HIV”
Reality:
 The majority of HIV
positive people on a
global scale are
heterosexual. Men infect
women and women infect
men. However:
 Gay men are at the most
risk in western cultures.

HIV
Myth:
“HIV can be spread through tears,
sweat, mosquitoes, pools, or
casual contact”
Reality:
 HIV can only be transmitted
through infected blood, semen,
vaginal fluids and breast milk.
The most common ways for
HIV to be transmitted are
through unprotected sexual
contact or sharing needles
with a HIV positive person.
 HIV can also be transmitted
from mother to baby during
pregnancy, birth or breast
feeding.

HIV
Myth:
“HIV can be spread through tears,
sweat, mosquitoes, pools, or
casual contact”
Cont.
Reality:
 The following “bodily fluids” are
NOT infectious:
 Tears
 Sweat
 Saliva
 Urine
 Faeces
 Casual contact is not considered
risky because it does not involve
contact with blood or other
infectious body fluids. Examples of
casual contact include:
 Kissing
 Sharing drinks/eating utensils
 Swimming pools
 Public toilets
 etc

HIV Transmission
 How HIV is spread is still misunderstood by many people.
 HIV is spread through the following body fluids:
 Blood (including menstrual blood)
 Semen and other male sexual fluids
 Vaginal fluids
 Breast Milk
 HIV is not spread through the following body fluids:
 Sweat
 Tears
 Saliva
How HIV Spreads

HIV Transmission
 In the past, HIV was spread in blood products. Many
people where infected this way. The blood supply is now
more strictly tested and controlled.
 You cannot get HIV from donating blood – a new and
clean needle is used for each donation.
 Some people, primarily those working in health care are
infected through ‘needle sticks’.
 Today, the most common ways HIV is transmitted are:
 Re-using and sharing needles
 Unprotected/unsafe sex (no condoms or other barrier devices)
 Mother-to-child (during pregnancy, birth or breast feeding).
Methods of transmission

HIV Transmission
HIV is not transmitted by:
 Hugs
 Dancing
 Sharing food or drinks
 Using a shower, bath or bed used by a HIV positive person
 Kissing (between people with no significant dental problems)
 Sharing exercise equipment
REMEMBER

Understanding the Immune System

 The immune system is made up of cells and organs
that protect your body from outside invaders such as
viruses, fungi, bacteria and parasites (germs), that can
cause infection, disease and death. The immune
system also functions to rid the body of abnormal
cancerous cells that are growing out of control. When
functioning properly, it fights off infection and keeps
you healthy. When in malfunctions, germs that enter
the body can more easily cause infections, disease and
death. Some important components of the immune
system are:
 Dendritic Cells
 T Cells
 Killer T Cells
 B Cells
 Neitrophilis

 Dendritic cells and macrophages
are the immune system’s first
line of defence. Dendritic cells
are found mostly in the skin and
mucous membranes that protect
the openings of the body (e.g.
the mouth and throat). These
cells capture and carry invaders
to the lymph nodes or spleen.
Macrophages (their name comes
from Latin and means “big
eaters”) protect different
organs, including the intestines,
lungs, liver, and brain.
 These two types of white
blood cells are known as
scavengers. They engulf
foreign invaders, break them
apart, and display pieces of
the intruders—known as
antigens—on their surfaces.
They also produce chemical
messengers (known as
cytokines) that instruct other
immune cells to go into action.
Dendritic Cells

 Once antigens are processed and
displayed on the surface of
macrophages, they can be
recognized by helper T cells (also
known as CD4 cells). When CD4 cells
“see” the antigens displayed, they
get busy and put the word out to
other immune system cells. In other
words, these cells coordinate and
direct the activity of other types of
immune cells—such as killer T cells,
B cells, and macrophages—calling
them into action to fight the intruder.
CD4 cells produce many different
cytokines in order to communicate
effectively with other immune system
cells.
 Killer T cells directly attack and destroy
cells infected by viruses as well as
abnormal cancerous cells. Yet another
type of T cell, called suppressor T
cells, calls off the immune system
attack once the invader is conquered.
(This is to make sure the killer cells
don’t go overboard, and relax once
their job is done). Both killer T cells
and suppressor T cells are also known
as CD8 cells.
T Cells

 B cells are another type of immune cell
that is activated by CD4 cells. When a
B cell recognizes an antigen, it goes
into action and produces antibodies
(also called immunoglobulins).
Antibodies are proteins that attach to
antigens like a key fits a lock. Each
antibody matches a specific antigen.
When an antibody matches up with an
antigen, it has in essence marked the
intruders for destruction by scavenger
immune cells. Antibodies also activate
a complex chemical chain reaction,
called the complement system. This
system’s purpose is to destroy
bacteria, which it essentially does by
punching holes in bacterial
membranes. which kills them.
 When you are exposed to a pathogen
for the first time, it usually takes awhile
(several weeks to a few months) for
your body to produce antibodies to fight
it. But if you were exposed to a germ in
the past, you will usually still have some
B cells (called memory cells) lingering in
your body that recognize the repeat
invader. This allows the immune system
to go into action right away. This also is
why people get some diseases, such as
chickenpox or measles, only once. And,
this is the basis for how vaccines work—
they cause your immune system to
produce antibodies even though you
have not actually had the disease. This
is why the expression “vaccinated
against” some disease (e.g., smallpox)
is used.
B Cells

 Neutrophils are another type of white
blood cell. They are made in the bone
marrow. When they are needed to fight
infection, they leave the marrow and
travel anywhere in the body to fight it.
These cells are your main defence against
bacteria. They eat bacteria and produce
toxic chemicals that destroy them.
Neitrophilis

 The immune system has special organs,
called lymph organs, that serve as a
home base for all of these white blood
cells. They are spread throughout the
body. Lymph organs include the bone
marrow and the thymus, as well as the
lymph nodes, spleen, tonsils and
adenoids, the appendix, and clumps of
tissue in the small intestine known as
Peyer's patches. (Some people would also
consider the blood and vessels that carry
these blood cells to and from the other
structures to be lymph organs.)
 Lymph nodes are located along the so-
called lymphatic routes. There are nodes,
or clusters, in the neck, armpits,
abdomen, and groin. Each lymph node
contains B cells, and T cells, and other
cells, ready to fight invaders.
 The spleen is a very important organ for a
healthy immune system. It is about the
size of a fist, and it is located at the upper
left of the abdomen. One of its most
important roles in the immune defence it
to help the body weed out and discard
worn-out white blood cells. It also houses
various white blood cells, waiting for
instruction to go out and fight infection.
 The lymphatic vessels carry lymph, which
is a clear fluid that “bathes” the body's
tissues, helping to clean out invaders or
germs. The vessels carry the fluid to the
lymph nodes, which can sort out the
antigens in order to begin the fight
against them.
Key Organs of the Immune System

 In HIV positive people, the virus attacks the
CD4 cells that coordinate the immune
response. This causes the CD4 cells to lose the
ability to communicate with the rest of the
immune system. Without CD4 cells organizing
the rest of the immune system, important
immune cells don’t know which invaders need
to be removed from the body. When this
coordination breaks down, people are at risk
for opportunistic infections and cancers that
usually do not harm people with healthy
immune systems.
 HIV can also infect macrophages and other
immune cells. Your immune system recognizes
and produces antibodies to HIV, but antibodies
alone are not enough to eliminate the virus.
This is partly because HIV mutates so rapidly
that it can change faster than the immune
system can respond to it.
 immune system and restore lost immune
function.
 Other problems may result from suppression of
the bone marrow, which can occur as a side
effect of certain HIV drugs like AZT (Retrovir).
The bone marrow is where immune cells are
produced, so when it’s suppressed, you may
have lower numbers of immune cells available,
which again may cause you to be a little more
vulnerable to infections.
 Effective combination HIV treatment can stop
the virus from replicating (making copies of
itself) and infecting more CD4 cells. Since CD4
cells are imperative to a healthy immune
response, this can give your immune system a
fighting chance to replenish its supply of CD4
cells and to defend itself against opportunistic
infections. Researchers are also studying new
HIV therapies that they hope will help repair the
damaged
HIV and the Immune System

Understanding Lab Tests
 A regular part of your HIV health care
involves having a sample of your blood
drawn for testing in a laboratory.
Laboratory tests are used to gauge
your HIV disease progression and the
overall health of your immune system.
Common tests include viral load, CD4
cell count, complete blood count,
blood chemistry tests (including liver
function tests), and blood fat and
sugar tests (lipid tests).
 When you are first diagnosed as HIV
positive or when you first start taking
HIV drugs (treatment), you should get
“baseline” tests that give a picture of
your health at that moment. Later
tests can be compared against these
results to see how things are going,
and if they are changing. Most
monitoring tests should be done every
three to six months, or as often as
your doctor recommends.
HIV Viral Load and CD4 Cell
Tests
 Viral load tests measure the
amount of HIV in your blood.
Your CD4 cell count measures
how many CD4 cells are in
your blood, reflecting the
health of your immune system.
Your doctor will usually look at
the results of both these tests
together, to get an idea of
whether your HIV disease is
progressing and whether your
treatment is working.

 Blood is made up of various types of cells and liquid. The complete blood count (CBC) is an
inventory of all the different cells. CBCs are important because some HIV drugs can cause low red
or white blood cell counts.
 Red blood cells (erythrocytes)
These cells carry oxygen to all the cells of the body. Oxygen, which you take into your body
through your respiratory system when you inhale, is vital for cells to live. Hematocrit and
hemoglobin tests are measures of how well red blood cells carry oxygen.
 White blood cells (leukocytes)
These cells carry out the body’s immune responses. A normal total white blood cell count is
4,000-11,000. The “differential” reports the proportions or relative amounts of different
types of white blood cells:
 Neutrophils
These white blood cells fight infections. A normal neutrophil proportion is about 50-70
percent. When your neutrophil count falls below about 500-750 cells (a condition called
neutropenia), you are more likely to get bacterial infections.
 Lymphocytes
There are two types of lymphocytes. B cells produce antibodies and T cells target cancerous
cells and cells infected with viruses. A normal lymphocyte proportion is about 20-40 percent.
CD4 and CD8 cells are types of T cells that are measured separately.
 Monocytes and macrophages
These cells engulf or “eat” and destroy foreign invaders, or disease-causing organisms. They
normally make up about 2-10 percent of all white blood cells.
 Eosinophils and basophils
These cells play a role in allergic reactions, and defend against parasites. They normally
make up about 1-8 percent of white blood cells.
 Platelets (thrombocytes) These cells are necessary for blood clotting. A normal platelet
count is about 130,000-440,000. If your platelet count is low, you may bleed or bruise
easily.
Complete Blood
Count

 Blood chemistry tests measure important substances in the blood. They can
help show how well organs like the liver and kidneys are working, and can
provide useful information about drug side effects. A blood chemistry
screen usually includes:
Electrolytes
 These particles play important roles in the healthy functioning of cells, nerves,
and organs. Specific electrolytes by name include bicarbonate, calcium, chloride,
magnesium, phosphorus, potassium, and sodium. Electrolyte imbalances may be
caused by not getting enough nutrients (malnutrition), kidney problems, or not
getting enough water into your body (dehydration, which can be caused, for
example by lots of vomiting or diarrhoea).
Liver function tests
 These tests help measure how well your liver is working. High levels of two key
liver enzymes—alanine transaminase (ALT or SGPT) and aspartate transaminase
(AST or SGOT)—may be a sign of liver damage. Normal levels for women are up
to about 40 for ALT and 35 for AST. Several HIV drugs can cause elevated liver
enzymes, so especially if you’re taking HIV drugs, your doctor will want to
monitor AST and SGOT levels in your body. High levels of bilirubin (a blood
pigment) may also indicate liver problems. A normal bilirubin level is 0-1.3.
Kidney function tests
 These tests help measure how well your kidneys are working. They include blood
urea nitrogen (BUN), creatinine, and uric acid. Kidney tests are especially
important if you are taking Viread (tenofovir).
Blood Chemistry Tests

 In recent years there has been a lot of talk about elevated fat (lipid) and
sugar levels in people taking HIV drugs. High blood fat levels can lead to
heart disease, while high blood sugar may be a sign of diabetes or insulin
resistance (when the body does not respond to insulin). Your doctor should
measure your blood fats and sugar regularly if you are on HIV treatment.
Exercise, changes in diet, and certain medications can help lower high
blood fat and sugar levels.
 Total cholesterol
Cholesterol is a fatty substance that circulates in the blood. A normal total
cholesterol level is 120-240. The U.S. government recommends that you should
try to keep your total cholesterol below 200.
 Low-density lipoproteins (LDL)
This is “bad” cholesterol, which can clog the arteries. You should try to keep your
LDL level below 100.
 High-density lipoproteins (HDL)
This is “good” cholesterol, which helps reduce the risk of heart disease. You
should try to get your HDL level up to at least 40.
 Triglycerides
After eating, energy that is not needed right away is converted into a substance
called triglycerides, which is stored in fat cells. A normal triglyceride level is
about 45-150. Very high triglyceride levels can cause pancreatitis (inflammation
of the pancreas, a serious condition).
Blood Fat and Sugar Tests

 Since many HIV positive people have no noticeable
symptoms of health problems, it is important to get
regular lab tests to monitor how you are doing. These
tests are valuable tools that can indicate if something is
wrong. CD4 cell counts and viral load test results can
help you make decisions about starting, stopping, or
switching treatments. Abnormal CBC, blood chemistry or
blood fat or sugar tests can indicate other health
problems that may be related to HIV or to HIV drugs
that you might be taking. Regular monitoring is an
important way to take charge of your health.
The Bottom Line

Diagnostic Tests
 Together with having regular medical care,
taking all prescribed doses of medication, and
maintaining a healthy lifestyle, the following
diagnostic tests can be very important in the
management of HIV. Speak to your doctor about
how you can use these tests to help make
treatment decisions.

Diagnostic Tests
 The CD4 count is usually the most important thing to
consider when you are deciding when to start HIV
treatment. You should have a baseline CD4 cell count
done as soon as you know you are HIV positive. Some
doctors recommend two baseline CD4 counts before
starting therapy, because CD4 counts can vary widely
from test to test. If two tests are done, and they are
very different, a third test should be done before starting
treatment.
 After starting treatment, you should have a CD4 count
done every three to six months.
CD4 Count

Diagnostic Tests
Viral Load
 Viral load is the amount of HIV in your bloodstream. It is measured by a polymerase
chain reaction or PCR test (also called a viral load test). Viral load tests are an
important tool to:
Monitor HIV progression:
 While CD4 cell counts are your best measurement of how healthy your immune
system is today, viral load tests can help you figure out if you’re at risk for more
immune damage in the near future. When compared over time, results will tell you
whether HIV is reproducing at a steady, fast, or slow rate. The higher your viral load,
the more likely you are to lose the valuable CD4 cells
Measure how well HIV drugs are working:
 HIV drugs work by preventing the virus from reproducing. If the drugs are working,
your viral load should go down. If there is a problem, your viral load may go up.
 The goal of HIV treatment is to keep viral load as low as possible for as long as
possible. With effective HIV treatment regimens, viral load can be reduced to levels
that cannot be detected by lab tests. With most viral load tests this is below 50
copies.

Diagnostic Tests
 Have a viral load test when you are
first diagnosed and every three to
four months when you are not on
HIV therapy.
 Have a viral load test before starting
treatment and again two to eight
weeks later. If the regimen is
working, your viral load should drop
by 90% within two months and be
undetectable (less than 50 copies)
within six months of starting
treatment. If these levels are
achieved, viral load is usually
measured every three to four
months.
 If these levels are not achieved
after starting treatment, or if your
viral load has recently become
detectable on stable therapy and
keeps increasing, it can signal that
your regimen isn’t controlling HIV
as well as it should. You and your
doctor should consider all possible
reasons (problems with absorption,
adherence, drug interactions, or
drug resistance) and take steps to
correct the problem, including
considering changing drug
treatments.
 Some doctors also recommend that
you have a viral load test two to
eight weeks after changing your
treatment regimen.
When should you get the Viral Load Test?

Diagnostic Tests
How to use your
laboratory tests and
your symptoms to
decide when to start
treatment
 The table on the right
shows how to use your
CD4 count, your viral
load, and your symptoms
to guide your decision
about when to start
treatment.
If… And… And…
your CD4
count is
greater than
350
your viral load
is less than
100,000
you have no
symptoms
therapy is not
recommended
your CD4
count is
greater than
350
your viral load
is greater than
100,000
you have no
symptoms
Most doctors would
advise you not to
start therapy yet,
but some may want
you to think about
starting therapy at
this point.
your CD4
count is
between 201
and 350
you have no
symptoms
you and your doctor
should decide
whether to start
treatment
your CD4
count is less
than 200
it is recommended
that you begin
treatment
you have
severe
symptoms,
or you have
an AIDS-
defining
condition
it is recommended
that you begin
treatment

Diagnostic Tests
Resistance Testing
 Resistance testing can be genotype or phenotype testing (see below). Resistance tests are used to determine
which drugs will work best against your virus. There are several types of resistance tests available. If your HIV
viral load is greater than 1000 or if you are considering changing your anti-HIV therapy, it is recommended that
you have resistance testing.
Genotype
 Genotype tests analyse the genetic makeup of your virus. They look for changes (mutations) in HIV’s enzymes
that can make it harder for drugs to work effectively. Your test result will list any mutations found.
 Each drug is associated with a mutation or mutations that can make that drug less effective. Some HIV drugs
don’t stop working unless several mutations are present.
 We still don’t know everything about these mutations, or which combinations of them are most problematic.
Because of this, it can sometimes be difficult to figure out how to make treatment decisions based on genotype
results.
Phenotype
 The phenotype test cultures (grows) your virus in a laboratory. It is then placed in test tubes containing samples
of the various HIV drugs. If a certain drug is not able to control the virus, more of that drug is added to the test
tube. Depending on how much drug is needed, the lab can determine how resistant the virus is to the drug.
 Phenotypic resistance results are reported as susceptible, sensitive, or less susceptible. Susceptible means that
the drug will probably work well. Sensitive means that the drug will work as expected in the average person and
less susceptible means the drug will probably not work very well for you.
 Phenotype test results are often easier to interpret than genotype tests.
Virtual Phenotype
 This is a genotype test that goes one step further – it uses phenotype data from many patients to predict
whether your virus will be sensitive or resistant to each of the HIV drugs.

Diagnostic Tests
 None of the resistance tests are perfect. They cannot detect every
mutation in your HIV or be used to predict exactly which drugs will
work for you. However, they are quickly becoming another tool to
determine treatment options in certain situations such as:
 In someone who is about to start HIV therapy for the first time and
whose HIV viral load is greater than 1000
 In someone who was just infected with HIV, also called acute infection
(testing is used to see if the person was infected with a drug-resistant
strain)
 In someone who is failing his or her current regimen (testing is used to
guide the choice of a new regimen)
 In a pregnant woman (testing is used to determine the best regimen to
prevent mother-to-child HIV transmission)
 All resistance tests that are taken after you have started HIV
therapy should be taken while you are still on HIV drugs (or within 4
weeks after stopping a regimen that is failing) to get the best
results.
Bottom Line for Resistance Tests

Diagnostic Tests
 When any drug is approved, a standard dose
is determined. This dose may be safe and
effective for most people, but for some
people, it may be more or less than needed.
If people get too little of an HIV drug, it may
be less effective and lead to the development
of resistance. If they get too much, they may
have problems with side effects.
 Therapeutic drug monitoring (TDM) measures
levels of drugs in the bloodstream. Based on
the results, doctors may be able to adjust
doses as necessary in different individuals.
Ideally, this should reduce side effects from
too much drug in the blood stream and
minimize the potential for drug resistance
from too little.
 Drug level testing may be particularly helpful
for HIV positive women. Some women have
higher levels of certain drugs in their
bloodstreams and experience more side
effects than men.
 These sex (male / female) differences may
be related to hormone changes that occur
when women get their periods. Drug level
differences also may be linked to basic
biology and physiology of cells (there are
differences in the cells of men and women).
They may also be linked to weight
differences.
 TDM is not approved for use with HIV drugs
yet and there are still unresolved issues
regarding the practical application of results.
But the hope remains that TDM can lead to
better-tolerated regimens and more
knowledge about HIV drugs in women
Therapeutic Drug Monitoring

Understanding CD4 & CD8 Cells
 CD4 and CD8 cells are white blood cells that play important roles in your
body’s immune response. Tests that count your CD4 and CD8 cells provide
a picture of your immune system health. Along with your viral load, your
CD4 cell count can help your doctor tell whether your HIV disease is
progressing or not, and how well your HIV drugs are working.
 CD4 cells (sometimes called T-helper cells)
These white blood cells help coordinate the various activities of your immune
system. HIV targets CD4 cells more than any other kind of cell in your body. A
normal CD4 cell count is about 600-1,500 cells. CD4 cell counts are often slightly
higher in HIV positive women compared to HIV positive men (viral load in HIV
positive women also tends to be slightly higher, relative to men, at the same
stage of disease). CD4 cell counts usually fall as HIV disease progresses.
 CD8 cells (T-suppressor or killer T cells)
There are two main types of CD8 cells. T-suppressor cells inhibit or suppress
immune responses. Killer T cells attack (“kill”) cancerous cells and cells infected
with viruses. A normal CD8 cell count is about 300–1,000 cells. CD8 cell counts
usually rise over time in HIV positive people, but why and how these increases
relate to the health of your immune system is not well understood.
The Basics

 Without HIV medication, the virus infects
more and more cells. This causes the CD4
count to decrease, usually by about 30 to
100 cells per year, in most HIV positive
people. As the CD4 count goes down, an
HIV positive person becomes more likely to
develop opportunistic infections (OIs) and
cancers.
 Above 500: People with CD4 counts above
500 cells usually have fairly normal immune
function and are at low risk for OIs
 Below 350: Current U.S. government
guidelines recommend that you should
consider HIV treatment when your CD4
count falls below 350 cells
 Below 200: A person with a CD4 cell count
below 200 cells is diagnosed as having AIDS.
The guidelines recommend starting
treatment at this point, if you have not
already done so
 People with low CD4 counts are prone to
developing OIs such as Pneumocystis
carinii pneumonia (PCP), Mycobacterium
avium complex (MAC), and
cytomegalovirus (CMV). As CD4 cells drop
below 200, your doctor will recommend
medications to prevent these infections.
 Many people have dramatic CD4 cell
increases when they start effective HIV
treatment. If the drugs succeed in
slowing or stopping HIV replication, fewer
new CD4 cells will be infected and the
CD4 count can recover—the “proof” of
which you see by the increasing numbers.
But the CD4 count can also fall again if
you stop taking your drugs correctly, or if
your HIV becomes resistant to the drugs.
So, your CD4 count is a very valuable tool
for monitoring your HIV disease
progression and how well your HIV
medicines are working.
CD4 Count and HIV

 CD4 and CD8 cell tests are simple blood
tests ordered by your doctor. When you are
first diagnosed as HIV positive or when you
first start treatment, you should get
“baseline” CD4 and CD8 cell tests. Baseline
tests give a current picture of your immune
system, when you first enter a doctor’s care.
Later tests can be compared against these
first results to see how things are changing
over time and with treatment.
 You should get your CD4 cell count checked
about every three to six months - or as
often as your doctor recommends. You may
need more frequent CD4 cell tests if your
count is low or falling, or if you are starting
or changing treatment.
 Many factors can affect your CD4 cell count,
including the time of day, stress, your
menstrual cycle, and infections such as the
flu. If you get a result or number back that
surprises you or your doctor, your doctor will
probably want you to get a second test. That
second test would confirm any unexpected
results or prove that those results were
random, sort of a fluke (that is, not
significant). Don’t worry too much about a
single abnormal test result; trends over time
are usually more important.
 In addition to CD4 and CD8 cell counts, your
doctor may also want to know your CD4 or
CD8 percentage. Percentages are usually
more stable than counts over time. A normal
CD4 cell percentage is about 30-60 percent,
and a normal CD8 cell percentage is about 20-
50 percent. Sometimes doctors also look at
the CD4/CD8 ratio. Healthy HIV negative
people usually have at least 1-2 CD4 cells for
every CD8 cell. But HIV positive people may
have many more CD8 cells than CD4 cells.
CD4 and CD8 Cell Tests

 Because HIV attacks CD4 cells,
CD4 counts usually drop as
HIV disease progresses. Taking
effective combinations of HIV
drugs may stop CD4 cell count
decreases and HIV disease
progression.
 Your CD4 cell count is an
important indicator of the
health of your immune system.
Tracking trends in your CD4
cell count can help you make
decisions about starting and
switching treatment. Getting
regular CD4 cell tests — along
with viral load tests and other
blood tests to monitor
treatment side effects — is an
important way to take charge
of your health.
The Bottom Line

Immune Reconstitution
 HIV can damage your immune system and
decrease your body’s natural ability to fight
infections. Immune reconstitution or restoration
refers to:
 Improving the body’s immune function
 Repairing the damage done by HIV
 Right now the main way to control HIV is by
taking powerful, and sometimes toxic, HIV drugs.
Successful immune reconstitution strategies might
allow the body to fight HIV more effectively on its
own. This could result in HIV positive people
being less dependent on HIV drugs.
 HIV Reduces the Number of CD4
Cells
 HIV attacks the immune system’s
soldiers – the CD4 cells. When the
immune system loses too many CD4
cells, you are less able to fight off
infection and can develop serious,
often deadly, infections. These are
called opportunistic infections (OIs)
because they take advantage of the
body's weakened defences.
 HIV Reduces the Type of CD4
Cells
 In a healthy immune system, there are
different types of CD4 cells that fight
different diseases. As HIV progresses
and kills off CD4 cells, some types of
CD4 cells can disappear, leaving gaps
in the immune system’s defences.
What is Immune Reconstitution? How does HIV Damage the
Immune System?

 One way to find out if you have
damage to your immune system is to
have a CD4 cell count done. This is a
routine blood test. If you have fewer
then 200 CD4 cells you are at
increased risk for OIs, and your doctor
will probably recommend that you
receive preventative therapy for
certain OIs. If your CD4 cells are
below 350, and you have not started
HIV treatment, you should probably
talk to your doctor about starting
treatment at that point.
 A viral load test can help predict how
quickly HIV may damage your immune
system. An increasing and/or high viral
load may mean that you are at greater
risk for immune damage.
 A simple test for hemoglobin or
hematocrit can determine if you are
anaemic. Anaemia can have a bad
effect on your immune system, so if
you are anaemic, it is important to
discuss with your doctor options for
treatment of your anaemia.
 Other immune function tests are in
development.
Monitoring the Health of the Immune System

 Many HIV positive people have
experienced restored immunity
(increases in CD4 cell counts) and a
delay in disease progression with the
use of HIV drugs. By keeping HIV
under control, these drugs protect the
immune system from further damage
and allow it to repair itself instead of
constantly fighting off HIV.
 One sign that the immune system is
getting stronger is an increase in CD4
cells. At first, the new CD4 cells are
probably copies of existing types of
CD4 cells. If some types of CD4 cells
were lost, they won't come back right
away. This could leave some gaps in
the body's immune defences.
 However, if HIV stays under control
for a few years, the immune system
might make new CD4 cells that could
fill in these gaps and more completely
restore immune function.
 Most people go on prophylaxis
(medications to prevent OIs) when
their CD4 cell counts go below 200.
However, if you take HIV drugs and
your CD4 cell count goes back over
200, it is usually safe to stop the
prophylaxis. (Speak to your doctor
before you stop taking any
medication.)
Using HIV Drugs to Restore Immune Function

 Several experimental strategies are being studied to restore immune function. These methods
focus on improving the function of various parts of the immune system:
Thymus
 The thymus is a small gland that turns certain white blood cells into CD4 cells, also called t-cells.
In fact, the “t” in t-cell stands for thymus. Scientists have studied transplanting a human or
animal thymus into an HIV positive person. They have also tried to stimulate the thymus with
hormones. To date these methods have not proven to be particularly successful.
CD4 Cells
 Various methods are being studied to increase and improve CD4 cell function:
 Cell Expansion – A person's cells are multiplied outside the body, and then infused back in.
 Cell Transfer – A person is given immune cells from their twin or an HIV- relative.
 Cytokines or Immune Modulators – These are proteins that our body naturally makes whenever there is an
infection. The most work has been done on a cytokine called interleukin-2 (IL-2). To date, trials have
shown that IL-2 significantly increases CD4 cells in HIV+ people; however the long-term benefits are still
unknown.
 Gene Therapy – This approach attempts to modify cells so that they are resistant to HIV infection.
Immune Response
 Therapeutic HIV vaccines may help the immune system to better recognize HIV. Many scientists
believe that this should improve and stimulate the body's response to the virus. Although data
released so far have been disappointing, several new types of therapeutic vaccines are being
studied in clinical trials.
Experimental Approaches to Immune Reconstitution

 Although an increase in CD4 cell counts is a good
sign, it has led to a flare up of certain types of
infections or a worsening of these infections in
some HIV+ people. This is referred to as immune
restoration inflammatory syndrome (IRIS). The
reported infections include Mycobacterium avium
complex (MAC), cytomegalovirus (CMV), herpes
simplex virus, hepatitis B and C, tuberculosis (TB),
and herpes zoster (or shingles).
 IRIS occurs in 15%-25% of people who are
starting therapy for HIV for the first time. IRIS
can occur when people with very weak immune
systems (e. g. people who have low CD4 cell
counts, high CD8 cell counts, or anaemia) start
HIV treatment or in people who start HIV
treatment when they already have an OI. If the
immune system recovers quickly after starting HIV
treatment, it might have a strong response to
some germs that were already in the body or new
germs with which it might come into contact.
 Although the outlook for most HIV positive
people with IRIS is good, IRIS has been
associated with some serious illnesses, so it
is important for you to discuss IRIS with
your doctor before you start HIV treatment.
Immune Restoration Syndrome

 Research into ways to enhance immune
reconstitution is ongoing. But for now, the
only way to improve and support the
immune system is with general health
maintenance like good nutrition, exercise,
and stress management, and, when
necessary, the use of HIV drugs to help
control the virus.
Taking Care of Yourself

Considering HIV Treatment
 HIV drugs can improve quality of life and
help HIV positive people stay healthier
longer. But starting treatment is a big
decision. In order to get the maximum
benefit from the drugs, you need to make a
commitment to taking them correctly.
Commitment to the treatment is as
important as the drugs themselves. So
before you get started, make sure that you
are ready to stick to it for the long haul!
This takes a combination of the right
doctor, enough knowledge about HIV, and
the right attitude.
 You and your doctor are a team working
together to make the best treatment
decisions for you. Ask yourself a few
questions: Can I be totally honest with my
doctor? Is he or she available when I have
questions? Does he or she take my
concerns seriously? If so, great!
 If not, try to make changes. Write down the
questions you’d like to ask your doctor
before you go to visits. Answer your
doctor’s questions with the truth, not with
what you think the doctor wants to hear. If
that still doesn’t work, it may be time to
find another doctor.
 It is also wise to have an HIV specialist for
your care. Doctors who devote most of
their time to HIV are best equipped to
manage this complicated condition.
Are you Ready? The Right Doctor

HIV Treatments
 Scientists have developed drugs that block HIV from
reproducing (multiplying) at different stages of its life
cycle. So far there are four classes of drugs:
 Fusion inhibitors
 Nucleoside/nucleotide reverse transcriptase inhibitors (“nukes”
or NRTIs)
 Non-nucleoside reverse transcriptase inhibitors (“non-nukes” or
NNRTIs)
 Protease inhibitors (PIs)
 These drugs are always used in combinations known as
HAART. HAART stands for highly active antiretroviral
therapy. HAART attacks HIV at different points using
different drugs (usually from different classes). This is the
best way to reduce the amount of HIV in your blood (viral
load).
Blood Tests
 Your doctor will use blood tests to monitor how you
are doing. The CD4 count checks the strength of your
immune system. The viral load test measures the
amount of virus in your blood. When you use HIV
drugs, you should see your viral load go down and
your CD4 count go up. That’s how you can tell the
medications are working.
Treatment Goals
 To get viral load as low as possible for as long as possible
 To preserve or regain immune system function by
increasing CD4 cells
 To improve quality of life and reduce illness and death
Treatment Guidelines
 The government has put together a list of guidelines
to help people decide when to start treatment:
 Anyone with symptoms of AIDS (such as opportunistic
infections) should start therapy
 Anyone with a CD4 count less than 200 should start
therapy
 People with a CD4 count greater than 350 and viral load
less than 55,000 can probably hold off on treatment
 The guidelines are less clear in other situations. You
and your doctor should review your numbers
frequently and consider the risks and benefits of
starting treatment earlier or later.
Knowledge

Benefits of Starting Early:
 Earlier and easier reduction of
viral load
 Delay or prevent a weakened
immune system
 Stay healthier longer
Risks of Starting Early:
 It can be hard to take drugs
everyday
 Drug-related side effects
 May reduce future treatment
options
 No one knows how long the
drugs will keep working
Benefits of Starting Later:
 Avoid negative effects on
quality of life
 Avoid drug-related side effects
 More treatment options for
the future
Risks of Starting Later:
 May have immune system
damage that cannot be
reversed or improved
 May be harder to bring down
viral load

 After starting HIV drugs, you
should see your viral load decrease
and your CD4 cells increase. Over
time, however, some people see
their viral load increase, even
though they are still taking HIV
drugs. When a drug becomes less
effective against HIV, we say that
HIV has become "resistant" to that
drug. If you develop resistance
you will have to change one or
more drugs in your regimen.
 In order to get the maximum
benefit from HIV therapy and
reduce the chances of developing
resistance, you must take your
drugs on schedule. This is called
adherence. Skipping doses, not
taking the drugs on time, and not
following food requirements can all
cause your drugs to be less
effective or to stop working
altogether.
Adherence
Resistance

 If you decide the time is right to start treatment, have a good
attitude going in. Believe that:
 Starting treatment is the right decision for you
 The HIV medications will help you fight the virus
 You can take your medications the right way
 What ever decision you make, don’t go it alone. Put together a
support system including your doctor, nurses, social workers, and
case managers. You may want to join a support group of other HIV
positive people. Family and friends can help too.
 The more you think and talk about your decision, the better the
outcome. What ever you decide to do, ensure you keep going to
your doctor for regular check ups and blood work.
The Right Attitude

Starting Treatment
 You’re about to start on HIV medications.
Having the right attitude going in will help
you get the most out of your treatment.
This means believing that:
 Starting treatment is the right decision for
you
 The HIV medications will help you fight the
virus
 You can take your medications the right way
 It takes a lot of energy and commitment to
stick to an HIV regimen. Don’t go it alone.
Your doctor is an important support and so
are other people such as nurses, social
workers, therapists, and case managers.
You may want to join a support group for
people taking HIV drugs. Family and
friends can help too.
 It can be tough to stick with a regimen if
you need to work on other issues in your
life. If you feel down a lot of the time,
and don’t enjoy things that you used to
enjoy, you may be depressed. That’s an
issue that must be addressed before you
start HIV therapy. The same goes for a
substance abuse problem.
 Tell your doctor if you have other health
problems, are taking any other
medications (including over the counter,
herbal, alternative and street drugs), or
are in any recovery programs. This is
important information that may affect
your treatment options. In addition,
discuss family planning with your doctor
since HIV medications can interfere with
birth control pills and pregnant women
should not take certain HIV drugs.

Starting Treatment
 The next step is for you and
your doctor to choose a drug
regimen. There are 24 drugs
approved for HIV treatment.
They fall into four classes:
 Fusion inhibitors
 Nucleoside/nucleotide reverse
transcriptase inhibitors
(“nukes” or NRTIs)
 Non-nucleoside reverse
transcriptase inhibitors (“non-
nukes” or NNRTIs)
 Protease inhibitors (PIs)
 There are many ways to combine
the drugs, but certain
combinations have been shown
to be the best for starting
therapy:
 A protease inhibitor (PI)-based
regimen or
 A “non-nuke” (NNRTI)- based
regimen
 An alternative to these regimens
is a regimen containing three
NRTIs. This option is not
normally used for people with
high viral loads (greater than
100,000) as first-line treatment
for HIV.
Choosing an HIV Drug Regimen

Starting Treatment
 With any HIV regimen, a major
problem is the development of
resistance. When HIV reproduces, it
copies its genetic information very
quickly. During this process, mistakes
(mutations) are made. Some of these
mutations keep HIV drugs from
working. When this happens, the virus
is “resistant” to that drug. Viral load
increases quickly if resistance occurs,
and you may have to switch regimens.
 In addition, if you become resistant to
one drug, you become resistant to
other drugs in the same class. This is
known as cross-resistance.
 One of the strategies in HIV therapy is
to think ahead. We know that
treatments may fail because of
resistance and cross-resistance. So
when you and your doctor choose your
first regimen, the two of you should
have already figured out what your
next regimens could be (even if these
change). This process is called
sequencing. It ensures that you will
have other treatment options available
if a regimen fails.
Sequencing
Resistance

Starting Treatment
 The best way to help prevent
resistance is with good adherence.
Your medications work best when
you take them exactly as they are
prescribed. When the drugs are
working, they slow down HIV
reproduction. This gives the virus
fewer chances to mutate, and
resistance is less likely to occur.
 It will be easier to adhere to your drugs if you set up a
dosing schedule that works for you. First, ask your doctor
– How many times a day should each dose be taken? How
many pills are in a dose? Are there any food requirements,
for example, take on an empty stomach or take with food?
 Then make your plan. If you take drugs in the morning
only, pick something that you do every morning, like
brushing your teeth or having a cup of coffee. Take your
drugs at that time.
 If your drugs are twice a day, pick another reminder at
night. Maybe you always watch the 11 o clock news or
have a cup of tea before you go to bed. Whatever you do,
add your drugs to your routine!
 If you have children, make sure your pill-taking schedule
fits in with their routines as well as your own.
 Track how well you are taking your pills by keeping a
journal or chart. Remember that everyone makes
mistakes. When this happens, you just need to start again
and commit to staying on track. But if you start missing
doses on a regular basis, tell your doctor.
Dosing Schedule
Adherence

Starting Treatment
 If no one knows about your HIV
status, taking medications is going to
be more difficult. You may feel like
you have to hide your pill bottles or
sneak out of the room when it’s time
for your dose. These challenges make
it harder to take your meds.
 This may be a good time to tell the
people close to you about your HIV
status. But if you’re not ready, put
everything in a pillbox and tell people
you take vitamins or medicine for
another condition.
 All HIV drugs have some side effects (but
not all people experience side effects). Side
effects are one of the major reasons that
people don’t stick to their HIV regimen. Be
prepared! Ask your doctor about the
possible short- and long-term side effects of
your particular regimen.
 There are medicines that can be used
against short-term side effects like nausea
and diarrhoea. Ask your doctor for
recommendations. You should have a
supply on hand before you start therapy.
 If you are having side effects, don’t just
stop your HIV drugs. This could have
serious health consequences. Talk to your
doctor about ways to deal with the side
effects, including switching to another drug
combination.
Side Effects
Privacy

Adherence
 The many advances in HIV
treatment in the past twenty years
have led to the approval of close
to 20 HIV drugs. Using these drugs
together in potent combinations
has helped many people control
their HIV and live longer and
healthier lives.
 However, the HIV drugs can
produce potent side effects. They
can also have complicated dosing
schedules and food restrictions.
This can make adherence (sticking
to your pill schedule) seem very
difficult to many people.
 Adherence to HIV medication is important. HIV
drugs need to be in your blood at certain levels to
be effective. Dosing schedules are designed to
maximize these levels. By not taking medicine on
schedule, you risk allowing drug levels to drop.
This may allow HIV to make copies of itself and
even make changes (mutations). These mutations
can help the virus survive, even in the presence of
HIV medication. This is called resistance.
 When HIV becomes resistant to a drug you are
taking, that drug will probably stop working. This
may lead to an increase in your viral load and a
decrease in your CD4 cell count. At that point, you
will probably have to switch to another HIV drug.
 Resistance to one drug can sometimes also cause
resistance to other drugs you have not taken.
(This is called cross-resistance.) Resistance can
affect your treatment options in the future by
reducing the number of drugs that will work
effectively against your virus.
 The best way to prevent resistance is to adhere
closely to your medication schedule. Some studies
suggest that 95 percent adherence may be
required to receive the most benefits from HIV
treatment.
The Importance of Adherence
Strong Drugs for HIV

Adherence
 Even though it may be embarrassing, it's
important to tell your doctor about the
number of times you have missed a dose
or did not take it correctly. He or she may
suggest a change in your dosing schedule
or drug regimen that makes it easier. In
recent years, some HIV drugs have
become available that require fewer pills
per day and have no food restrictions.
There are also new ways to combine
older drugs that make them easier to
take.
 Side effects are an important factor in
determining whether someone continue
on their HIV drugs. While all of the HIV
drugs can cause side effects, not
everyone will experience them. It is a
good idea to find out what side effects to
expect before you start your drugs. Then
ask your doctor how to manage minor
side effects if they arise. You may want to
stock up on doctor-recommended
treatments for common side effects like
nausea or diarrhoea.
 If you do experience a side effect, don’t
just stop taking your pills. Follow the
recommendations given by your doctor. If
the problem persists, speak to your
doctor about other solutions, including
switching drugs.
Overcoming Barriers

Adherence
 Believe that the medications will
help you fight the virus and stay
well. If you don't think so, you won't
bother taking your pills right. If you
have any doubts, speak to your
doctor. Ask your doctor or
pharmacist to explain exactly how to
take your pills and give you written
instructions.
 Use a daily activity, one that you do
every day without fail (like waking
up in the morning or going to bed at
night), to remind you to take your
pills. When it’s time to do that
activity, you will know that it’s also
time to take your pills.
 If you don’t want others to see you
taking your pills, quietly slip away to a
secluded area or the bathroom. If that
won’t work, say the medications are
for another health problem or that
they are vitamins.
 If you suspect substance use or mental
health issues are preventing you from
taking your medications correctly, talk
to your physician or case manager so
they can get you help. There are good
treatments available.
 Take advantage of tools available from
your clinic or pharmacy such as
pillboxes, calendars, diaries, and
beepers to help you remember to take
your medications.
Adherence Tips

Adherence
 Adherence is hard work and takes
a lot of commitment. It helps to
have other people on your side.
One way to do this is to put
together a support network. Your
doctor is one of the most
important people in your network.
Talk openly with him or her about
how to fit HIV treatments into
your lifestyle.
 There are many other sources of
information and support available
to women who are taking or
thinking about taking HIV
treatments. If you can, include
family, friends, case managers,
treatment educators, and
counsellors in your network. You
can also get involved with your
local AIDS service organization or
a support group. These are places
where you will be able to ask
questions and share experiences.
When you are feeling
discouraged, turn to your network
for support and encouragement.
Finding Support

Drug Interactions
 The body metabolizes (breaks down) the drugs you take. This
process involves the liver and kidneys:
 Proteins in the liver called enzymes break down the drug
 The kidneys remove the drug from the bloodstream
 The drug is eliminated from the body in urine or faeces
 Sometimes, one drug affects the way another drug is metabolized.
This is called an interaction. Some interactions do not cause
problems and may even be beneficial. However, some interactions
decrease a drug’s effectiveness and increase side effects.
 Potential drug interactions should be taken into consideration when
selecting a new HIV regimen or when any new drug is added to an
existing regimen.
What is a Drug Interaction?

Drug Interactions
 Some drugs inhibit (slow down) the action of the
liver enzymes. This causes other drugs to be
metabolized and eliminated from the system more
slowly, which:
 Increases the amount of other drugs in the body
 Increases the length of time other drugs stay in the
bloodstream
 This can be useful in HIV therapy. For example,
the protease inhibitor (PI) Norvir (ritonavir)
significantly slows down the liver enzymes. Low
doses of Norvir are often used to increase or
“boost” the concentration of other PIs. This can
make the other PI work so much better that you
can take fewer doses and fewer pills.
 Unfortunately, increased blood levels of drugs can
also cause overdoses or increased side effects. If
you are taking a drug that slows down liver
enzymes, your doctor may need to adjust the
doses of your other medications.
 Some drugs induce (speed up) the action of
the liver enzymes. This causes other drugs
to be metabolized and flushed out of the
system more rapidly, which:
 Decreases the amount of other drugs in the
body
 May cause other drugs to be less effective
 Some drugs used to treat HIV-related
conditions speed up the liver enzymes. This
can be a serious problem if it causes the
HIV drugs to be metabolized too quickly. If
HIV drug levels drop too low:
 HIV can multiply
 Viral load can go up
 Resistance can develop
 HIV drugs can stop working
 If you are taking a drug that speeds up liver
enzymes, your doctor may need to increase
the doses of your other medications.
Drugs that Slow Down Metabolism Drugs that Speed Up Metabolism

Drug Interactions
Complementary Therapies
 Many HIV positive people use
complementary therapies such as vitamins
or herbs. While most of these have not
been studied with HIV drugs, St. John’s
Wort (an herbal anti-depressant) and garlic
supplements have been shown to decrease
levels of PIs. Make sure to tell your doctor if
you take any complementary therapies.
Recreational Drugs and Alcohol
 There have been reports of overdoses,
some fatal, caused by taking recreational
drugs and HIV drugs. Interactions between
ecstasy or amphetamines (crystal meth,
speed) and PIs are particularly dangerous.
 Alcohol affects body processes and is often
responsible for drug interactions. Combining
alcohol and certain HIV drugs like ddI can
put you at risk for developing pancreatitis
(inflammation of the pancreas).
Methadone
 Methadone can interact with many HIV
drugs. Tell the doctor at the methadone
program and your HIV doctor what you
are taking. This way necessary
adjustments can be made to insure you
get enough methadone to prevent
withdrawal symptoms and enough HIV
drugs to fight the virus effectively.
Food
 What you eat can affect how much of
your drugs get into your system. Certain
drugs need to be taken on an empty
stomach and others work better with
food. Check your drug labels and follow
the food instructions carefully.
Specific Interactions
There is a list of some drugs that may have significant
interactions with HIV medications. Below are a few examples:

Drug Interactions
 If you are having problems with side
effects or drugs not working well, it may
be helpful to have your drug levels
checked using a test called Therapeutic
Drug Monitoring (TDM). If your levels
are too high or too low, your doctor may
adjust your doses or switch some of your
medications. (At this point, TDM is not
widely used in HIV treatment.)
 HIV positive people often have to take
many different drugs. To get the best
results, it is a good idea to:
 Keep a list of all your drugs (including
prescription, over-the-counter, vitamins,
supplements, herbs, and recreational drugs)
and ask your doctor to review it for possible
interactions
 Give a copy of your drug list to all of your
health care providers
 Discuss all your medical conditions with your
doctor
 Each time you are prescribed a new
medication, check with your doctor to see if
it can be combined safely with your other
therapies
 Have all your prescriptions filled at one
pharmacy
 Learn about all the possible side effects of
your drugs
 Learn how, when, and with what to take
your drugs
 Don’t stop or change your drugs without
talking to your doctor
 Report any side effects to your doctor
Therapeutic Drug Monitoring

Side Effects
 While all the HIV drugs can cause side effects, not everyone will
experience the same effect to the same extent. Speak to your
doctor before starting any new treatment to find out what kinds of
side effects are possible. It will help if you know what to expect and
how to handle any problems that arise.
 Some important points:
 Side effects are most common in the first four to six weeks after
starting a new medication
 After your body gets used to a new drug, the side effects usually lessen
or go away
 Have doctor-recommended treatments for common side effects like
diarrhoea and nausea on hand
 Let your doctor know if you are experiencing side effects, especially if
you are taking a drug that may cause a particularly serious problem
Side Effects and HIV Drugs

Side Effects
 Some side effects (examples following this slide), appear
to be more common in HIV positive women than men.
This may be due to the fact that women have higher
levels of certain HIV drugs in their bloodstreams, even
though they take the same doses as men. A woman’s
smaller body size, metabolism, or hormones may cause
the higher levels. For example, with the PI (protease
inhibitor) Norvir, women seem to experience more
nausea and vomiting but less diarrhoea than men.
Despite the difference in drug levels and side effects,
women seem to benefit as much from HIV therapy as
men. No changes in dosing have been recommended for
women.

Side Effects
 The term lipodystrophy is used to describe a
number of body shape changes and metabolic
problems that can occur in HIV positive people.
While HIV positive men and women both
experience body shape changes, women are
more likely to experience fat gain in the breasts
and stomach.
 Some of the symptoms of lipodystrophy have
been linked with heart disease and strokes, so
make sure to go to your doctor regularly and have
your cholesterol, triglycerides, and blood pressure
monitored. You can also support your body, and
especially your heart, with a healthy diet, regular
exercise, and giving up smoking.
 Lipodystrophy can dramatically alter your
appearance. If you are concerned about how you
look, speak to your doctor before making any
changes to your HIV medication schedule that
might jeopardize your health.
 Rash is a very common side effect of the
non-nucleoside reverse transcriptase
inhibitor (NNRTI) class of HIV drugs such as
Viramune (nevirapine) and Sustiva
(efavirenz). Rashes are more common and
more severe in women.
 If you start Viramune, take half the full dose
for two weeks (lead-in period), then go up
to the full dose. If you develop a rash, you
should contact your doctor. Your doctor may
recommend that you not increase to the full
dose or, if the rash is too uncomfortable,
your doctor may tell you to stop taking the
drug. In rare cases, the rash can be so
severe that it becomes life threatening, a
condition called Stevens-Johnson syndrome.
Lipodystrophy Rash

Side Effects
 Anaemia is a shortage of red blood cells that can be
caused by some of the HIV drugs. Women are at higher
risk for developing anaemia than men.
 If left untreated, anaemia is strongly associated with HIV
disease progression and an increased risk of death.
Fortunately, the effects of anaemia can be greatly
reduced with treatment. Tell your doctor if you are
experiencing extreme fatigue so you can be tested for
anaemia.
 Being a HIV positive woman puts you at higher risk for
bone disease such as osteoporosis and osteopenia.
These diseases cause weaker bones that can break more
easily. Talk to your doctor about the following methods
of protecting your bones:
 Have your bone density checked with a DEXA scan
 Get enough calcium and vitamin D
 Exercise
 Stop smoking
 Reduce your intake of caffeine and alcohol
 Lactic Acidosis is a build up of lactic acid in the
blood. It is a rare but serious complication of the
NRTI (nucleoside reverse transcriptase inhibitor)
class of HIV drugs, such as d4T and ddI. Women
(especially pregnant women), overweight people,
and those with a long history of NRTI use are
more likely to develop lactic acidosis.
 Symptoms include fatigue, nausea, vomiting,
stomach pain, shortness of breath, and weakness
in the arms and legs. If you notice any of these
symptoms, call your doctor right away
Anaemia and Fatigue
Bone Problems
Lactic Acidosis

Side Effects
 HIV drugs have helped many people live longer,
healthier lives. To get the most out of the drugs,
it is important to take them correctly and be
aware of potential side effects. If you have
difficulty with a drug, don’t just stop taking it.
Speak to your doctor. There is usually
something that can be done about it, such as
changing to another drug, altering the dose of
that drug, or treating the side effect separately.

Resistance
 HIV drugs are designed to keep your viral load under
control by preventing the virus from reproducing.
However, sometimes HIV is able to overcome the effects
of a drug and keep reproducing anyway. When this
happens, we say that HIV has developed resistance to
that drug.
 Resistance is a major challenge in HIV therapy. Resistance
decreases control over HIV and knocks out your treatment
options. The best way to prevent resistance is to adhere
to your HIV drug regimen. With good adherence,
resistance is less likely to develop. This will keep more
treatment options open to you in the future.
 After infecting a CD4 cell, HIV reproduces itself. It makes
many new viruses that infect other cells. This process
happens very quickly – HIV can make up to 10 billion new
viruses every day! During reproduction, HIV must copy its
genetic information. Copying happens so fast that
mistakes are made. These mistakes are called mutations,
and they occur randomly.
 Some mutations are harmless. They produce weak viruses
that can’t infect other cells. But other mutations cause big
problems – they prevent certain HIV drugs from working
effectively. If a drug doesn’t work against a mutated virus,
the virus will reproduce rapidly. This can cause the viral
load to go up, and it may be necessary to change drugs to
get HIV back under control.
 One of the reasons to use strong combination therapy for
HIV is to block reproduction as much as possible. With
less reproduction, mutations and resistance are less likely
to occur.
 Resistance to certain classes of HIV drugs can develop
more easily than resistance to other classes. For example,
HIV only needs one particular mutation to become
resistant to all the NNRTIs (drugs like Sustiva [efavirenz]
and Viramune [nevirapine]). Resistance to other classes,
like the protease inhibitors (PIs), is more difficult to
develop. Two or more mutations are required before
resistance to PIs occurs.
What is Resistance?
What Causes Resistance?

Resistance
 Resistance is very common. Studies have
shown that 12 percent of people who are
newly infected with HIV get a strain that is
already resistant to one drug (most people are
still infected with “wild-type” virus or virus that
is not resistant to any drugs). Six percent of
patients get a strain resistant to two or more
drugs. This means that newly-infected people,
who have never taken any drugs, may already
have a limited selection of HIV treatments due
to resistance.
 HIV positive people who have already received
HIV therapy are even more likely to have
resistant virus. One study showed that 78
percent of patients who have been treated
were resistant to one drug. Fifty-one percent
of patients were resistant to two or more
drugs.
 Cross-resistance is another challenge to
consider. Some mutations cause resistance
not to just one drug, but to an entire class of
drugs. For example, certain mutations causing
AZT resistance also cause resistance to most
of the other NRTIs. In addition, resistance to
one NNRTI leads to resistance to all currently
available NNRTIs. This may limit treatment
options when it is time to pick a new regimen.
 If you are starting a treatment regimen for
the first time, you should ask your doctor
about sequencing. Sequencing is like a “game
plan” for HIV therapy. Your doctor should not
only choose what you will start with, but what
drugs you can switch to if your first regimen
stops working. In other words, you and your
doctor should be thinking about your second
and third possible regimens while planning
your first HIV drug combination. This should
leave several good drug options open for the
years ahead.
How Common is Resistance? Cross-Resistance and Sequencing

Resistance
 There are several ways to test for resistance:
 Genotype test
 This test uses HIV from your blood to check the genetic
sequence of the virus for mutations associated with
drug resistance
 Phenotype test
 This test challenges your virus with all HIV drugs (in a
test tube) to determine which ones are still effective
against your HIV
 Virtual phenotype test
 This is a genotype test that goes one step further – it
uses phenotype data from many patients to predict
which drugs will be effective against your virus (and its
mutations)
 Resistance tests are helpful when choosing a new
regimen. The tests are only a guide, however. Other
factors, such as past medications, side effects, and
adherence must be taken into account.
 Resistance tests can be useful in the following
situations:
 Someone who was just infected with HIV (acute
infection)
 Testing is used to see if the patient was infected with a
drug-resistant strain
 Someone who is failing his or her current regimen
 Testing is used to guide the choice of a new regimen
 A pregnant woman
 Testing is used to determine the best regimen to
prevent mother-to-child HIV transmission
 The best way to avoid resistance is to follow your
medication regimen closely. Try not to skip doses.
Also, try to take your meds at the same time every
day. If you follow your doctor’s instructions, you
give the drugs a chance to work as well as possible.
 Although resistance may seem overwhelming,
remember that you have the power to help prevent
it. If you follow your medication schedule, the virus
will not reproduce as quickly. And if it’s not
reproducing, it can’t make the mistakes that lead to
resistance. This will keep treatment options open
for the future!
Resistance Testing
Avoiding Resistance

Pharmacokinetics (PK)
 Pharmacokinetics, also known as PK, is the study of
how medications behave in and move through the
body. PK is used to figure out how much drug gets
into your bloodstream and how long it stays there.
 Scientists study PK to determine the best dose for
an HIV drug. The dose must be high enough to
keep HIV from reproducing, but not so high that it
causes many side effects.
 The following PK values are important:
 Maximum concentration (Cmax): highest drug level. When a drug is
given, it reaches its peak level in the blood (Cmax) pretty quickly. The
drug level then decreases as the drug is broken down and removed
from the blood.
 Minimum concentration (Cmin): lowest drug level. The lowest drug
level, right before the next dose, is the (Cmin), or “trough” level.
 Area Under the Curve (AUC): total drug exposure. The total exposure
to the drug with each dose is called the AUC. (This refers to the
graph of the drug level in the blood over time.)
 Half-life (t1/2): drug half-life. The t1/2 of the drug is the amount of
time required for half of the drug to be removed from the
bloodstream. For example, if the dose of a drug is 100 milligrams
(mg), and the half-life is eight hours, 50 mg will be left after eight
hours.
 The PK values are used to figure out the correct dose – both
the amount of drug and the schedule (once a day, twice a day,
etc). In order for a drug to work, it must have a high enough
minimum concentration (Cmin) and total exposure (AUC) to be
effective against HIV.
 It is also important to avoid toxic side effects. If the maximum
concentration (Cmax) gets too high, the drug can cause many
side effects. The goal of HIV therapy is to get the most benefit
from the drug with the fewest side effects.
 Last but not least, the half-life of the drug must be long enough
to allow for a reasonable dose schedule. Many drugs are being
developed with a long enough half-life so that they only need to
be taken once a day.
What is PK?
How is PK studied?

 Liver proteins called enzymes help with drug
processing. Enzymes affect drugs by breaking them
down. But enzymes are also affected by drugs.
 This has proven to be very useful in HIV therapy.
Here’s an example: Norvir (ritonavir) is a protease
inhibitor (PI) that makes the enzymes work slower.
This keeps other drugs in the body longer. So if
Norvir is given with another PI, like Crixivan
(indinavir), it “boosts” Crixivan. The minimum
concentration (Cmin) and total exposure (AUC) of
Crixivan are both increased.
 As a result, Crixivan can be given twice a day with
a little Norvir instead of three times a day by itself.
The boosted regimen makes Crixivan easier to take.
Several other PIs can be boosted with Norvir.
 The NNRTIs (drugs like Viramune [nevirapine] and
Sustiva [efavirenz]) have the opposite effect. They
speed up enzymes and get other drugs out of the
system faster. As a result, higher doses of other
drugs may be required.
 Doctors are aware of these interactions and will
make sure you get the right doses. That’s why it is
important to let your doctor know about all the
medications and supplements you are taking
(including herbs, prescriptions, over-the-counter,
and street drugs).
 There are some PK differences in men and women. At the
same doses, some women have higher levels of certain
drugs in their bloodstreams and experience more side
effects (especially rashes) than men. Despite the
differences, women seem to benefit as much from HIV
therapy as men.
 These PK sex (male / female) differences may be related
to hormone changes that occur when women get their
periods. PK differences also may be linked to basic
biology and physiology of cells (there are differences in
the cells of men and women). They may also be linked to
weight differences. Standard doses of drugs are usually
based upon research done predominantly in men. This
means a woman, who will generally weigh less than a
man, may get a higher amount of the drug in her body
than is needed to be effective. Although differences
between men and women have been seen in studies, no
changes to dosing have been recommended for women.
If you are experiencing side effects, ask your
doctor for help. Do not change your dose or stop
your drugs without speaking to your doctor.
 Other factors can also affect PK, including:
 Genetic differences in drug processing
 Food
 Tobacco and alcohol use
 Medication interactions
 Race
 Hepatitis or other liver problems
Drug Interactions and
Drug Boosting
Do Men and Women Process
Drugs Differently?

 Because of PK differences, new tests are
being developed to help figure out if
patients are receiving the right amount of
drug.
 Therapeutic Drug Monitoring (TDM): TDM
is designed to measure your drug levels
specifically. Basically it measures
minimum concentration (Cmin) by
drawing blood before morning meds. This
will help your doctor to decide if your
dose of medication should be changed.
 Inhibitory Quotient (IQ): The IQ of a drug
shows us how much drug should be
necessary to inhibit the virus effectively.
The IQ is different for each drug. This
concept is still being proven.
 The timing of medication doses has
been carefully calculated to keep the
drug in your bloodstream at levels that
will control HIV. When you do not take
a dose on time, the blood level of the
drug will fall too low to be effective.
 When this happens your HIV may
become resistant to the drug you are
taking, causing it to stop working. Your
viral load could go up, your CD4 cells
could go down, and you might need to
change drug treatments. The best way
to avoid this is to take your pills the way
they are prescribed. This maintains the
blood level of the drugs necessary to
fight the virus effectively.
Pharmacokinetic Testing How to Make PK Work for You

AIDS Vaccines
 A vaccine is a treatment that teaches
our immune system how to protect
itself against a disease-causing germ
like a virus or bacteria. Vaccines are
one of the world’s most effective tools
for preventing diseases. Polio,
smallpox, measles, and mumps have
been nearly eliminated from many
countries because of vaccines.
 Ideally, an AIDS vaccine would
prevent people from being infected
with HIV (the virus that causes
AIDS).
 Today there are no effective AIDS
vaccines.
 There are more than 20 trials of
roughly 15 different vaccine
candidates going on in nearly 15
countries around the world. The
majority of these trials are small
“Phase I” safety studies. There is one
large-scale efficacy trial underway in
Thailand. This “Prime-Boost” trial is
testing how well a combination of two
vaccines called ALVAC and AIDSVAX
works. Another mid-size efficacy trial
of a vaccine developed by Merck is
also under way.
 Each vaccine being tested uses a
slightly different design or strategy but
none of the candidates can actually
cause HIV infection. This is because
they only use copies of small pieces of
HIV.
What is a vaccine?
Is there an AIDS vaccine?
What is the state of AIDS
vaccine research?

AIDS Vaccines
 The honest answer is that we don’t know. It
takes several years to evaluate whether a
vaccine candidate is safe and effective. This
means that it will be at least five to seven
years before we find out whether any of the
current candidates can protect people from
HIV infection. If not, it will take even more
time to develop and evaluate second- or
third-generation candidates. Although this
sounds discouraging, remember that many
epidemics in the modern era have been
ended with an effective vaccine. And it took
several decades to find most of these
vaccines, starting from the point that the
disease-causing germ was first identified. So
it’s important to keep moving ahead with
AIDS vaccine research.
 The best case is that an AIDS vaccine is found
which can provide very high levels of protection
from HIV infection in nearly everyone who
receives it. But many scientists think that the first
and even second generation of AIDS vaccines that
are developed will provide more limited forms of
partial protection. These might include:
 Improving overall health and slowing down disease
progression in people who receive the vaccine and
later become infected.
 Protecting some, but not all, of the people who
receive the vaccine against becoming infected.
 The concept of partial protection is not unique to
AIDS vaccines. Most people think of vaccines in a
fairly straightforward way: once you are
immunized against a particular disease, you are
completely protected for life. In fact, this is not
always the case. None of the vaccines that are
currently licensed for use are 100 percent
protective in 100 percent of the people who
receive them. Some vaccines work better in some
people than in others; other vaccines only provide
protection for a limited amount of time.
How long will it take to find
an AIDS vaccine that works?
What could an AIDS vaccine do?

AIDS Vaccines
 AIDS vaccines are not tested by deliberately exposing people to
HIV. Like all experimental medicines or vaccines, AIDS vaccine
candidates go through a series of safety tests—first in animals
and then in small groups of people. These small studies help
determine whether or not the vaccine causes any serious side
effects. Only vaccines that appear to be completely safe are
considered for large-scale “efficacy” trials that test whether the
vaccine protects against HIV infection in healthy, HIV negative
people.
 Before an efficacy trial begins, researchers usually spend two or
more years studying communities where trials may take place.
They gather many types of information, including how many
people get HIV each year. The rate of new infections is called
the incidence rate. If 100 HIV negative people were followed for
one year, and five of them got HIV by the end of the year, you
could say that there was a 5 percent incidence rate in that
group of people.
 Once these numbers have been collected, people from the
community are asked to enrol in the vaccine trial; they are
randomly assigned to receive either the vaccine or a placebo
(an inactive substance). Neither the researchers nor the trial
volunteers know who has received the vaccine and who has
received the placebo.
 The volunteers are followed for a long period of time—usually
two to three years. At the end of the trial, the researchers look
to see whether the incidence rate is lower in the group of
people who were given the vaccine, as compared to the group
of people who were given the placebo.
 For example, if there was a 2 percent incidence rate in people
who received the vaccine, and a 5 percent incidence rate in
people who received the placebo, that might mean that the
vaccine was protecting some people against HIV.
 Yes. Vaccine trials provide a lot of information to
people who are thinking about volunteering, and to
people who decide to enrol in the trial. One of the
key messages is that there is no way of knowing
whether the vaccine is effective, so it is important
that everyone who decides to take part in the trial
continues to protect themselves using existing
methods like condoms or clean needles. This
message is repeated to volunteers every time they
visit the study site; some trials will also conduct
surveys of volunteers to find out whether it has been
communicated clearly and effectively. By continually
educating volunteers, it is possible that the vaccine
trial reduces the volunteer’s risk. All trials also provide
free male condoms and counsel volunteers about
other methods like the female condom or safe
injection practices.
How are AIDS vaccines tested?
Do vaccine trials do anything
to help reduce the volunteer’s risk
of becoming infected with HIV?

AIDS Vaccines
 Right now, most of the candidates that are
being developed are preventive vaccines
that are designed to be used by HIV
negative people. However there are a few
trials that are testing therapeutic vaccines in
HIV positive people to find out whether the
vaccine can strengthen their immune
defences against the virus.
 Although AIDS vaccines are going to be
tested first in adults and, perhaps,
adolescents, an effective vaccine could
someday be given to infants born to women
with HIV to help protect them from getting
HIV through breast milk. This would be
most useful in developing countries where
formula feeding is not possible for many
women with HIV.
 Over 20 years into the epidemic, we still don’t
have ways to protect ourselves against HIV
infection during sex that are private, woman-
controlled, and do not depend on our partners’
agreement. There is an urgent need for
prevention methods that women can choose
without necessarily asking permission from their
partners. An effective AIDS vaccine would give
women this option. A woman could decide to be
immunized against HIV; later on, she might
decide to talk about the decision with her
partner—or she might not. The choice would be
up to her.
 In order to find an AIDS vaccine that helps
protect us, women should be represented in
substantial numbers in all AIDS vaccine trials.
This is the only way that researchers will be
able to find out whether a particular vaccine
works equally well in women as compared to
men. Looking for evidence of sex-specific
differences is especially important when it
comes to vaccines that aim to protect against
sexual transmission of HIV. This is because
differences in men’s and women’s sexual
anatomy influence HIV transmission, and could
potentially translate into different levels of
protection from a vaccine.
I have HIV —
why do AIDS vaccines matter to me?
Why do AIDS vaccines
matter to women?

RIGHTS
 Although you are not
obliged to tell anyone
your status, the law may
require you to tell people
under certain
circumstances.
 In some states, you are
legally required to tell any
sexual partner, even if you
intend to have safe sex.
The laws vary from state to
state.
 HIV positive people
cannot donate:
 Blood
 Semen
 Ova
 Any other body tissues
 The department of
immigration requires
anyone applying for
permanent residency to
provide results of a HIV
test

RIGHTS
 As a HIV positive person,
you may be asked about
your HIV status when
applying for life insurance
or by your
superannuation fund.
Some companies may
refuse to insure you if
you are HIV positive, or if
you refuse to disclose
your status.
 As a HIV positive person,
you have many legal
rights to protect you from
discrimination. You
cannot be refused any of
the following, based on
your HIV status:
 A job
 Housing
 Medical services
 Dental Services

RIGHTS
 Discrimination based on HIV
status is illegal throughout
Australia under Commonwealth
law and some states have their
own, separate legislation to
protect against HIV/AIDS
related discrimination.
 It is illegal to discriminate on the
grounds of:
 Employment
 Education
 The provision of goods
 Services and facilities
 Accommodation
 Buying or selling property
 Club membership
 Sport and administration of
Commonwealth programs
 The law also protects people who are
believed to be HIV positive and
people who associate with HIV
positive people.

Thank You!
 A special thank you must go to http://www.thewellproject.org for
allowing me to utilise so much of their website in the creation of this
presentation. Even though their website is targeted at women, the
research is relevant to anyone living with this disease.
Again, thank you guys. The use of your information is greatly appreciated.

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