LECTURE NINE

Expected Learning Outcomes

At the end of this lecture the learner should be able to:
1. Explain the role of anti-retroviral therapy in HIV and Aids management
2. To identify antiretroviral regime and describe the initiation process
3. Describe the goals of ARVs
4. Discuss the working mechanism for ARVs

ART (ANTI-RETROVIRAL THERAPY)

ART are medications that treat HIV. The drugs do not kill or cure the virus.
However, when taken in combination they can prevent the growth of the virus.
When the virus is slowed down, so is HIV disease. Antiretroviral drugs are referred
to as ARV

Once HIV identified as the cause of AIDS, stopping or slowing the replication of the
virus became a major goal. Significant progress has been made towards reaching
this goal. Particularly with the arrival of potent drugs and the use of combination
therapy that has made it possible to develop long-term strategies for the management
of HIV.

The objectives of anti HIV therapy are to:

 Prolong life and improve quality of life for the long term.
 Suppress virus to below the limit of detection on the currently available tests
(below 50 copies of HIV RNA), or as low as possible, for as long as possible.
 Optimise and extend the usefulness of the currently available therapies.
 Minimise drug toxicity and manage side effects and drug interactions.
It is important to remember that people can live for a long time, without symptoms
of HIV disease, without the use of ant-HIV therapy

Thus many (if not most) people do not have to make a decision about using ant-HIV
therapy immediately after learning that they are living with HIV.

Assessing personal risk of HIV disease progression and making decisions that one
feels comfortable with and empowered by is part of the key to a successful long term
ant HIV strategy. When a person is first infected with HIV, high virus levels develop
that are often accompanied by flu-like symptoms and a decline in the number of
CD4+ cells. These are key cells in maintaining and directing immune responses
against disease. They are also a common measure of immune health.

Without the use of ant-HIV therapies, the immune system produces a dramatic but
in-complete suppression of the virus. In most cases, CD4 + cells counts return
partially toward normal levels and a person usually regains good health for many
years.

Studies demonstrate that even during his time of seemingly good health, there is an
aggressive battle waged daily between HIV and the immune system.

Over time, the immune system is overwhelmed by the virus rapid and constant
activity.

There is clear relationship between increased levels of HIV found in blood (viral
load), more advanced disease states and increased risk of disease progression. As a
general rule, the more virus being produced in the body, the more rapidly disease
progresses. Several studies have now shown that when viral load is reduced and
CD4+ cell counts increases for six months or longer, disease progression and death
are delayed.

Considering this, it makes sense to attempt to slow or stop the replication of HIV as
much and for as long as possible. A number of drugs have been shown to
significantly reduce viral load, and these drugs almost always cause some rise in
CD4+ cell counts.

The reduction in viral load and increase in CD4 + cell counts indicate some
improvement in the immune system. Anti-HIV drugs that fall to reduce viral load
also generally (but not always) fail to improve measures of immune health such as
CD4+ cell counts.

The Highly Active Antiretroviral Therapy (HAART)

Combination ARV therapy (cART) is referred to as highly active ART (HAART).

Working mechanism
HIV cannot survive and perform the usual functions living organisms require to
perform, outside a living human cell. For the virus to continue living and
multiplying, it needs to enter a human cell and harness the cell’s usual biologic
survival mechanisms. This process if facilitated by viral replication enzymes which
are themselves components of the virus. The enzymes important in viral replication
are;
 Reverse transcriptase.
 Integrase.
 Protease.
Antiretroviral drugs inhibit the replication of HIV by blocking the actions of the viral
replication enzymes. When antiretroviral drugs are given in combination, HIV
multiplication and immune deterioration can be delayed. New viruses are not
produced, and as the infected human cell die, either from the effects of the virus or
as they complete their life span, the amount of viruses in the blood continues to
reduce overtime. When there are no ‘free’ viruses in the blood, the new T-
lymphocytes and the new cells that are produced do not become infected. And
overtime, there is accumulation of Healthy T-cells, ensuring better immune function
and improved survival and quality of life for the person using ARVs.

Importance of HAART

Effective HIV & AIDS Care requires antiretroviral therapy as a treatment option.
Without access to antiretroviral therapy, may negative consequences can be
observed for instance;

 The life expectancy of people infected with HIV ill be too short because many
people will die from the complications of HIV disease just like it happened
prior to the introduction of ART, and in many regions in the world where ART
is not accessible today.
 Health care workers will remain disempowered. Disempowered comes when
health care workers fell that they cannot do much for the patients suffering
from HIV disease. When health care workers are disempowered, they are not
motivated to care for the people suffering from HIV disease. This can
sometimes make them neglect such patients in favour of caring for those who
are likely to recover from their illness.
  Children will be orphaned earlier. As the parents die from the complication of
HIV infection, and AIDS disease, they leave behind children too young to
fend for themselves.
 Stigma and discrimination will continue. Diseases that are perceived to
definitely lead to death are associated with higher levels of stigmatization.
Stigma leads to very negative effects which also hinder prevention efforts.
The two laboratory tests used most commonly to monitor the success of
antiretroviral therapies are measures of the viral load and the T-lymphocytes (T-
helper or CD4+) cell count.

Viral load: this is concentration of the virus in the blood. With some types of highly
active antiretroviral therapy (HAART). It is possible to reduce the amount of virus
circulating in the blood to below levels that are not detectable.

Unfortunately, in such cases the virus is still present in the body and the
concentration of circulating virus will increase if treatment is stopped. If the viral
load decreases, then begins to increase, this may be an indication of non-compliance
with medications, resistance of the virus to the antiretroviral drugs, or treatment
failure.

The T-helper (CD4+) cell count; Is a specified amount of WBC’s in the patient’s
blood. The CD4+ cells are severely affected by HIV infection. In the body, HIV
attaches to and enters CD4+ cells. Once inside, the virus subverts the CD4+ cell’s
replication machinery, turning it into a virus factory. In the process of copying itself,
the virus destroys the CD4+ cell.

Determining a patient’s CD4+ count at regular intervals allows the health

professional to monitor the strength of the patient’s immune system. Successful
antiretroviral therapy will cause the CD4+ cell count to rise and then remain elevated
during therapy. A decrease in the concentration of the CD4+ cells may represent
failure of antiretroviral therapy.

Goals of HAART

1. The primary goal of antiretroviral therapy is to improve the health and prolong
the life of the HIV infected individual. This is achieved by interfering with the
ability of the virus to multiply (replicate) inside the body. When the virus is
 unable to replicate, damage to the immune system is minimised. Due to the
immune system functioning more normally, the treated individual is less likely
to suffer from opportunistic infections including cancers.
2. HIV infected people receiving antiretroviral therapy are also less likely to
develop other complications associated with HIV and AIDS, such as wasting
syndrome and brain disorder (Erophalophathy). Most people taking antiretroviral
therapy are likely to live longer than they would without them.
3. For children who are infected with HIV, effective treatment with ARV’s will
often result in improved growth and development.
Initiation of ART

Antiretroviral therapy is not necessarily started when a patient is first infected with
HIV. Although some evidence suggests that starting medicines before a patient is
symptomatic can prolong life, there are many obstacles to such early treatment
because;

 Antiretroviral therapy can be costly.

 The virus can develop resistance to these medications.
 The medicines can be difficult to take because of the many side effects.
 Patients who do not feel ill may not be motivated to take their medication.
 Once antiretroviral medicines are started, they need to be taken consistently
and continuously, every day, according to instructions. Therefore, a patient’s
motivation is important to ensure that medication schedules are followed
precisely.
With challenges such as these in mind, most clinicians who treat adults follow
standard criteria for starting medications, which may include the following;

 Symptoms of HIV infection, such s fungal infections or weight loss.

 Viral load of more than 500 copies/ml of plasma.
 CD4+ count of less than 350cell/µ of blood.
Many developing countries have chosen to utilize a higher viral load and lower CD4 +
cell count for initiating antiretroviral medications.

Timing of Art Initiation

ART should be started in all patients as soon as possible; but not later than 2 weeks
after confirmation of HIV infection
Same day ART initiation for following populations:
 Pregnant and breastfeeding women
 Infants
 Positive partner of a discordant partnership
 Patient preparedness assessment to be conducted
 Guidance on adherence support for same day initiation and continued follow
up included
In Kenya, general guidelines suggest that HIV infected individuals should start ARV
therapy when;

 The victim has clinical AIDS, regardless of CD4+ count.

 The total CD4+ count cannot be assessed; in addition, people with WHO stage
II or III HIV disease should be offered treatment.
 The CD4 counts are available; all HIV infected patients with less than 200
CD4+ cell/mm3 should be offered treatment.

SUMMARY
We have now managed to describe the role of anti-retroviral therapy in HIV and
Aids management. We have also identified antiretroviral regime and describe the
initiation process. Further we have been able to describe the goals of ARVs and
their working mechanism.

Further reading

Refer to the ART Guidelines (2016) Table 6.4: Common significant adverse drug
reactions

Activity
Visit the Kenya National Aids & STI Control Program (NASCOP), World
Health Organization (WHO) and USAID websites and write short notes
maximum one page on existing guidelines before initiation of Anti-retroviral
therapy.