C h a p t e r 1 6
Disorders of the Immune Response
365
doubling time of approximately 0.3 days during the first
2 to 3 weeks of infection.
The problem is that, over years, the CD4
+
T-cell
count gradually decreases through this process, and
the number of viruses detected in the blood of persons
infected with HIV increases. The depletion of CD4
+
T cells after infection is due to the cytopathic effect of
the virus, resulting from production of viral particles,
as well as death of unaffected cells. Other infected
cells, such as macrophages and dendritic cells, may also
die, resulting in destructive changes in the lymphoid
organs. Until the CD4
+
T-cell count falls to a very low
level, a person infected with HIV can remain asymp-
tomatic, although active viral replication is still taking
place and serologic tests can identify antibodies to HIV.
These antibodies, unfortunately, do not convey protec-
tion against the virus. Although symptoms are not evi-
dent, the infection proceeds on a microbiologic level,
including the invasion and selective destruction of CD4
+
T cells. The continual decline of CD4
+
T cells, which
are pivotal cells in the immune response, strips the HIV-
infected person of protection against common organ-
isms and cancerous cells.
Classification and Stages of HIV Infection
The definitions and classification systems for HIV and
AIDS have been evolving, due in part to improvements
in diagnostic and therapeutic capabilities, including
increased use of new HIV-testing technologies. In 1993,
the Centers for Disease Control and Prevention (CDC)
developed a classification system that emphasized the
clinical importance of the CD4
+
T-cell count along with
a list of AIDS-defining conditions (Chart 16-3).
56
The
1993 classification system, which was revised in 2008,
highlights the central importance of the CD4
+
T-cell
count and percentages, which are objective measures of
immunosuppression routinely used in the care of HIV-
infected persons
57
(Table 16-2). It distinguishes three
stages of HIV infection based on CD4
+
T-cell counts and
total T-cell percentages: stage one >500 cells/
μ
L (29%);
stage two 200 to 499 cells/
μ
L (14% to 28%); and stage
three (AIDS) <200 cells/
μ
L (<14%). An undetermined
stage has also been included.
Clinical Course.
The typical course of HIV infection is
characterized by three phases, which usually occur over
a period of 8 to 12 years. These are the primary infec-
tion phase, chronic asymptomatic or latency phase, and
overt AIDS phase (Fig. 16-9).
56
When initially infected with HIV, many persons
have an acute mononucleosis-like syndrome known
as
primary infection.
This acute phase (stage 1) may
include fever, fatigue, myalgias, sore throat, night
sweats, gastrointestinal problems, lymphadenopathy,
maculopapular rash, and headache. Fever and malaise
are the symptoms most commonly associated with pri-
mary infection.
46,57
During primary infection, there is
an increase in viral replication, which leads to very high
viral loads, sometimes greater than 1,000,000 copies/
mL, and a decrease in the CD4
+
T-cell count. The signs
and symptoms of primary HIV infection usually appear
1 to 4 weeks after exposure to HIV, and have an aver-
age duration of 7 to 10 days.
57
After several weeks, the
immune system acts to control viral replication and
reduces the viral load to a lower level, where it often
remains for several years. This relatively stable level
of virus is referred to as the set point. People who are
diagnosed with HIV infection while they are in the pri-
mary infection phase may have a unique opportunity
for treatment. Some experts hypothesize that treatment,
if started early, may reduce the number of HIV-infected
CD4
+
memory T cells; protect the functioning of HIV-
infected CD4
+
T cells and cytotoxic T cells; and poten-
tially help to maintain a homogeneous viral population
that will be better controlled by antiretroviral therapy
and the immune system.
46,58
CHART 16-3
Conditions Included in the 1993 AIDS
Surveillance Case Definition
Candidiasis of bronchi, trachea, or lungs
Candidiasis, esophageal
Cervical cancer, invasive*
Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal (>1 month
duration)
Cytomegalovirus disease (other than liver, spleen, or
nodes)
Cytomegalovirus retinitis (with loss of vision)
Encephalopathy, HIV related
Herpes simplex: chronic ulcer(s) (>1 month duration)
or bronchitis, pneumonitis, or esophagitis
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal (>1 month’s duration)
Kaposi sarcoma
Lymphoma, Burkitt (or equivalent term)
Lymphoma, immunoblastic (or equivalent term)
Lymphoma, primary, of brain
Mycobacterium avium-intracellulare complex
or Mycobacterium kansasii, disseminated or
extrapulmonary
Mycobacterium tuberculosis, any site (pulmonary* or
extrapulmonary)
Mycobacterium, other species or unidentified species,
disseminated or extrapulmonary
Pneumocystis jiroveci pneumonia
Pneumonia, recurrent*
Progressive multifocal leukoencephalopathy
Salmonella septicemia, recurrent
Toxoplasmosis of the brain
Wasting syndrome due to HIV
*Added to the 1993 expansion of the AIDS surveillance case
definition.
From Centers for Disease Control and Prevention. 1993
Revised classification system for HIV infection and expanded
surveillance case definition for AIDS among adolescents and
adults. MMWR Recomm Rep. 1992;41(RR-17):19.
