Acquired (Secondary) Immune Deficiencies

HIV Infection and AIDS

 Pathophysiology
Human immune deficiency virus (HIV) infection and disease can
progress to acquired immune deficiency syndrome (AIDS), which is the
most common immune deficiency disease and is now a serious
worldwide epidemic (World Health Organization [WHO], 2013).

Etiology and Genetic Risk

The cause of HIV infection is a virus—the human immune deficiency virus.
HIV is a parasite looking for a way into a cell, to take over the cell, and to
force the cell into making more copies of the virus (viral particles). These
new viral particles then look for additional cells to infect, repeating the
cycle as long as there are new host cells to infect.

The HIV Infectious Process.

Viral particle features include an outer envelope with special “docking
proteins,” known as gp41 and gp120, that assist in finding a host (Fig. 19-
1). Inside, the virus has genetic material along with the enzymes reverse
transcriptase (RT) and integrase. The HIV must get inside a host cell. It
does this by first entering the host's bloodstream and then “hijacking”
certain cells, especially the CD4+ T-cell, also known as the CD4+ cell,
helper/inducer T-cell, or T4-cell (see Chapter 17). This cell directs immune
system defenses and regulates the activity of all immune system cells.
When HIV enters a CD4+ T-cell, it can then create more virus particles.
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 Virus-host interactions are needed after infection for disease development.
When a person is infected with HIV, the virus randomly “bumps” into
many cells. The docking proteins on the outside of the virus must find
special receptors on a host cell for the virus to bind and then enter the
cell. The CD4+ T-cell has surface receptors known as CD4, CCR5, and
CXCR4 (Fig. 19-2). Proteins on the HIV particle surface, known as gp120
and gp41, recognize these receptors on the CD4+ T-cell. For the virus to
enter this cell, both the gp120 and the gp41 must bind to the receptors.
The gp120 first binds to the primary CD4 receptor, which changes its
shape and allows the gp120 to bind to either the CCR5 co-receptor or the
CXCR4 co-receptor. Once co-receptor binding occurs, gp41 inserts a
fusion peptide into the T-cell membrane, boring a hole to allow insertion
of viral genetic material and enzymes into the host cell. This attachment
allows the virus to then enter the CD4+ T-cell (see Fig. 19-2). Viral binding
to the CD4 receptor and to either of the co-receptors is needed to enter the cell.
(The drug class known as entry inhibitors works here to prevent the
interaction needed for entry of HIV into the CD4+ T-cell.)
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 After entering a host cell, HIV must get its genetic material into the
host cell's DNA. HIV is a retrovirus, which is able to insert its singlestranded
ribonucleic acid (ss-RNA) genetic material into the host's DNA.
The genetic material of the human cell is double-stranded DNA (ds-
DNA). To infect and take over a human cell, the genetic material must be
the same. The HIV enzyme reverse transcriptase (RT) converts HIV's ss-
RNA into ds-DNA, which makes the viral genetic material the same as
human DNA. (The drug classes known as nucleoside reverse transcriptase
inhibitors [NRTIs] and non-nucleoside reverse transcriptase inhibitors
[NNRTIs] work here to prevent viral replication [Fig. 19-3] by reducing
how well reverse transcriptase can convert HIV genetic material into
human genetic material.) HIV then uses its enzyme integrase to get its
DNA into the nucleus of the host's CD4+ T-cell and insert it into the
host's ds-DNA. This action completes the infection of the CD4+ T-cell.
(The drug class known as integrase inhibitors works here to prevent viral
DNA from integrating into the host's DNA.)
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HIV particles are made within the infected CD4+ T-cell, using all the
metabolic machinery of the host. The new virus particle is made in the
form of one long protein strand. The strand is clipped by the enzyme HIV
protease into smaller functional pieces. These pieces are formed into a
new finished viral particle. (The drug class known as protease inhibitors
works here to inhibit HIV protease.) Once the new virus particle is
finished, it fuses with the infected cell's membrane and then buds off in
search of another CD4+ T-cell to inafect (see Fig. 19-3).
Effects of HIV infection are related to the new genetic instructions that
now direct CD4+ T-cells to change their role in immune system defenses.
The new role is to be an “HIV factory,” making up to 10 billion new viral
particles daily. In addition, the immune system is made weaker by
removing some CD4+ T-cells from circulation. In early HIV infection
before HIV disease is evident, the immune system can still attack and
destroy most of the newly created virus particles. With time, however, the
number of HIV particles overwhelms the immune system. Gradually,
CD4+ T-cell counts fall, viral numbers (viral load) rise, and without
treatment, the patient eventually dies of opportunistic infection or cancer.
Everyone who has AIDS has HIV infection; however, not everyone who has
HIV infection has AIDS. The distinction is the number of CD4+ T-cells and
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whether any opportunistic infections have occurred. A healthy adult
usually has at least 800 to 1000 CD4+ T-cells per cubic millimeter (mm3)
of blood. This number is reduced in the person with HIV disease.
Some people develop an acute infection within 4 weeks of first being
infected. Manifestations of this acute HIV infection can be fever, night
sweats, chills, headache, and muscle aches, which are similar to those of
any viral infection—not just HIV. A sore throat and rash also may
accompany this acute HIV infection. With time, these symptoms cease
and the person feels well again, although a “war is going on” between
HIV and the immune system.
As time passes, more CD4+ T-cells are infected and taken out of
service. The count decreases, and those that remain function poorly. Poor
CD4+ T-cell function leads to these immune system abnormalities:
• Lymphocytopenia (decreased numbers of lymphocytes)
• Increased production of incomplete and nonfunctional antibodies
• Abnormally functioning macrophages
As the CD4+ T-cell level drops, the patient is at risk for bacterial,
fungal, and viral infections, as well as opportunistic cancers. Opportunistic
infections are those caused by organisms that are present as part of the
body's normal environment and are kept in check by normal immune
function. They occur because of the profound immunosuppression in the
person with AIDS.
A diagnosis of AIDS requires that the person be HIV positive and have
either a CD4+ T-cell count of less than 200 cells/mm3 or less than 14%
(even if the total CD4+ count is above 200 cells/mm3) or an opportunistic
infection. Once AIDS is diagnosed, even if the patient's T-cell count goes
higher than 200 cells/mm3 or if the percentage rises above 14%, or the
infection is successfully treated, the AIDS diagnosis remains and the
patient does not revert to being just HIV positive.

HIV Classification.
The Centers for Disease Control and Prevention (CDC) currently defines
four stages of HIV disease. In this definition, laboratory confirmation of
HIV infection (by enzyme-linked immunosorbent assay [ELISA] and
Western blot analysis) plus CD4+ T-lymphocyte count or percentage and
the presence or absence of the 27 AIDS-defining conditions (Table 19-1)
determine the classification (Centers for Disease Control and Prevention
[CDC], 2013b). The person with HIV infection can transmit the virus to others
at all stages of disease, but the recently infected person with a high viral load
and those at end stage without drug therapy can be particularly infectious.
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TABLE 19-1
Centers for Disease Control and Prevention Classification of Aids-Defining
Conditions in Adults

Stage 1 CDC Case Definition describes a patient with a CD4+ T-cell count
of greater than 500 cells/mm3 or a percentage of 29% or greater. A
person at this stage has no AIDS-defining illnesses.
Stage 2 CDC Case Definition describes a patient with a CD4+ T-cell count
between 200 and 499 cells/mm3 or a percentage between 14% and
28%.
 A person at this stage has no AIDS-defining illnesses.
Stage 3 CDC Case Definition describes any patient with a CD4+ T-cell
count of less than 200 cells/mm3 or a percentage of less than 14%. A
person who has higher CD4+ T-cell counts or percentages but who
also
has an AIDS-defining illness meets the Stage 3 CDC Case
Definition.
Stage 4 CDC Case Definition is used to describe any patient with a
confirmed HIV infection but no information regarding CD4+ T-cell
counts, CD4+ T-cell percentages, and AIDS-defining illnesses is
available.
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HIV Progression.
The time from the beginning of HIV infection to development of AIDS
ranges from months to years. The range depends on how HIV was
acquired, personal factors, and interventions. For people who have been
transfused with HIV-contaminated blood, for example, AIDS often
develops quickly. For those who become HIV positive as a result of a
single sexual encounter, the period is much longer before progression to
AIDS. Other personal factors that influence progression to AIDS include
frequency of re-exposure to HIV, presence of other sexually transmitted
diseases (STDs), nutrition status, and stress.