C h a p t e r 1 6
Disorders of the Immune Response
363
Transfusions of whole blood or blood products
before 1985 resulted in the transmission of HIV. Since
1985, all blood donations in the United States have
been screened for HIV, dramatically reducing the trans-
mission risk to an extremely small number.
2
Currently,
all donated blood and plasma are screened for HIV-
associated antigen and antibodies to HIV. Screening
tests may be negative in the so-called
window period
,
the 1 to 6 months following a new HIV infection and
before seroconversion, the point at which HIV antibod-
ies can be detected in the blood. Therefore, the U.S.
Food and Drug Administration (FDA) requires blood
collection centers to screen potential donors through
interviews designed to identify behaviors known to
present a risk for HIV infection. In addition, nucleic
acid amplification testing (NAAT) of blood donors has
reduced the risk of transfusion transmission of both
HIV and hepatitis C virus to approximately 1 in 2 mil-
lion blood units.
51
Occupational HIV infection among health care
workers is uncommon. Universal blood and body
fluid precautions should be used in encounters with all
patients in the health care setting because HIV status is
not always known. Occupational risk of infection for
health care workers most often is associated with per-
cutaneous inoculation (e.g., needle stick) of blood from
a patient with HIV infection. Transmission is associated
with the size of the needle, amount of blood present,
depth of the injury, type of fluid contamination, stage
of illness of the patient, and viral load of the patient.
The average risk for HIV infection from percutaneous
exposure to HIV-infected blood is about 0.3%, and
about 0.09% after mucous membrane exposure.
52,53
The HIV-infected person is infectious even when no
symptoms are present. The point at which an infected
person converts from being negative for the presence of
HIV antibodies in the blood to being positive is called
seroconversion.
Seroconversion typically occurs within
1 to 3 months after exposure to HIV, but rarely can take
as long as 6 months. Recent data suggest that 50% of
transmissions occur during primary HIV infection and
early HIV infection.
54
The time after infection and before
seroconversion is known as the
window period.
During
the window period, a person’s HIV antibody test result
will be negative but he or she can still transmit the virus.
Molecular and Biologic Features of HIV
Infection
The primary etiologic agent of AIDS is HIV, an envel-
oped ribonucleic acid (RNA) retrovirus that carries its
genetic material in RNA rather than DNA. Two geneti-
cally different but antigenically related forms of HIV—
HIV-1 and HIV-2—have been isolated in people with
AIDS.
1–3
Human immunodeficiency virus-1 is the type
most commonly associated with AIDS in the United
States, Europe, and central Africa, whereas HIV-2
causes a similar disease principally in western Africa.
Human immunodeficiency virus-2 spreads more slowly
and causes disease more slowly than HIV-1. Specific
tests are now available for HIV-2, and blood collected
for transfusion is routinely screened for HIV-2. The
remaining discussion focuses on HIV-1, but the infor-
mation is generally applicable to HIV-2 as well.
HIV infects a limited number of cell types in the body,
including CD4
+
T lymphocytes, macrophages, and den-
dritic cells (see Chapter 15). The CD4
+
T cells are nec-
essary for recognition of foreign antigens, activating
antibody-producing B lymphocytes, and orchestrating
cell-mediated immunity, in which cytotoxic CD8
+
T cells
and NK cells directly destroy virus-infected cells, tuber-
cle bacilli, and foreign antigens. The phagocytic func-
tion of monocytes and macrophages is also influenced
by CD4
+
T cells.
The HIV is spherical and contains an electron-dense
core surrounded by a lipid envelope
1–3
(Fig. 16-8A). The
core contains an outer shell, or capsid, made up primar-
ily of a protein called p24; two copies of the genomic
RNA; and three viral enzymes (protease, reverse tran-
scriptase, and integrase). The viral core is surrounded
by a matrix protein called
p17
, which lies beneath the
viral envelope, a structure studded with two viral gly-
coproteins, gp120 and gp41, which are critical for the
infection of cells.
Replication of HIV occurs in eight steps
2,3
(see
Fig. 16-8B). Each of these steps provides insights into the
development of methods used for preventing or treat-
ing the infection. The
first step
involves the binding of
the virus to the CD4
+
T cell. Once HIV has entered the
bloodstream, it attaches to the surface of a CD4
+
T cell
by binding to the CD4 molecule, which acts as a high-
affinity receptor for the virus. This process is known as
attachment.
However, attaching to the CD4 molecule
is not sufficient for infection; the virus must also bind
with other surface molecules (chemokine coreceptors,
such as CCR5 and CXCR4) that bind the gp120 and
gp41 envelope glycoproteins. The chemokine corecep-
tors are critical components of the HIV infection pro-
cess: the virus can only infect cells expressing CD4
+
and
the coreceptors. People with defective coreceptors are
more resistant to development of HIV infection, despite
repeated exposure.
55
Research aimed at developing core-
ceptor-targeted viral entry inhibitors raises new hope for
bridging the gap toward a cure of HIV infection.
The
second step
of the replication process allows for
internalization of the virus. After attachment, the viral
envelope peptides fuse to the CD4
+
T-cell membrane.
Fusion results in an
uncoating
of the virus, allowing the
contents of the viral core (the two single strands of viral
RNA and the reverse transcriptase, integrase, and pro-
tease enzymes) to enter the host cell. The
third step
con-
sists of DNA synthesis. In order for HIV to reproduce,
it must change its RNA into DNA. It does this using
the
reverse transcriptase
enzyme. Reverse transcriptase
makes a copy of the viral RNA, and then in reverse
makes a complementary DNA (cDNA) strand. The
result is a double-stranded DNA that carries instruc-
tions for viral replication.
The
fourth step
is called
integration.
In dividing cells,
the cDNA enters the nucleus and, with the help of the
enzyme integrase, is inserted into the cell’s original DNA.
The integrated virus is called a
provirus
. In quiescent
