370
U N I T 4
Infection and Immunity
The mitochondria control many of the oxidative
chemical reactions that release energy from glucose and
other organic molecules and transform it into adenosine
triphosphate (ATP), which cells use as an energy source.
In the absence of normal mitochondrial function, cells
revert to anaerobic metabolism, generating lactic acid.
The mitochondrial disorders seen in persons with HIV
infection are attributed to a class of drugs called the
nucleoside/nucleotide analog reverse transcriptase inhib-
itors
(NRTIs), particularly the thymidine analogs.
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The
most common presentations are lipoatrophy and periph-
eral neuropathy, although patients may not experience
both. Patients may also present with nonspecific gastro-
intestinal symptoms, including nausea, vomiting, and
abdominal pain. They may develop altered liver function
and lactic acidosis. Since the recognition of the ascend-
ing polyneuropathy syndrome and reports of hepatic
failure due to combination therapy with stavudine and
didanosine, reports of life-threatening events due to
mitochondrial toxicities have dramatically decreased.
Diagnosis andTreatment
A diagnosis of HIV infection may be prompted by
a number of scenarios, including positive results of a
screening test, accompanying signs and symptoms of an
acute HIV infection, or manifestations of an immuno-
deficiency state. Unfortunately, there are approximately
250,000 persons living with HIV infection in the United
States who are not aware of their infection or their risk
of transmitting it, and therefore are missing the oppor-
tunity to benefit from early treatment.
Diagnostic Methods.
The most accurate and inex-
pensive method for identifying HIV infection is the
HIV antibody test. The first commercial assays for
HIV were introduced in 1985 to screen donated
blood. Since then, use of antibody detection tests
has been expanded to include evaluating persons at
increased risk for HIV infection. The HIV antibody
test procedure consists of screening with an
enzyme
immunoassay
(EIA), also known as
enzyme-linked
immunosorbent assay
(ELISA), followed by a con-
firmatory test such as the
Western blot assay,
which
is performed if the EIA is positive.
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The EIA detects
antibodies produced in response to HIV infection. In
an EIA, antibodies to HIV in the blood sample bind to
HIV antigens in the test material.
56
The Western blot
is a more sensitive assay than the EIA that looks for
the presence of antibodies to specific viral antigens.
56
In the case of a false-positive EIA result, the Western
blot test can identify the person as uninfected.
Polymerase chain reaction
(PCR) is a technique for
detecting HIV DNA (see Chapter 14). Polymerase
chain reaction detects the presence of the virus rather
than the antibody to the virus, which the EIA and
Western blot tests detect. Polymerase chain reaction
is useful in diagnosing HIV infection in infants born
to infected mothers because these infants have their
mothers’ HIV antibodies regardless of whether the
children are infected. Polymerase chain reaction is
also useful in determining acute HIV infection as the
antibody tests are negative in early infection.
Technologic advances have led to new forms of
testing, such as the oral test, home testing kits, and
the new rapid blood test. Oral fluids contain antibod-
ies to HIV. In the late 1990s, the FDA approved the
OraSure test. The OraSure uses a cotton swab, which
is inserted into the mouth for 2 minutes, placed in a
transport container with preservative, and then sent to
a laboratory for EIA and Western blot testing. Home
HIV testing kits can be bought over the counter. The
kits, approved by the FDA, allow persons to collect
their own blood sample through a finger-stick pro-
cess, mail the specimen to a laboratory for EIA and
confirmatory Western blot tests, and receive results
by telephone in 3 to 7 days. In November 2002, the
FDA approved the Ora Quick Rapid HIV-1 Antibody
Test.
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The Ora Quick uses a whole-blood specimen
from a fingerstick and can provide results in about
20 minutes. Reactive, or positive, test results require
confirmation using Western blot testing on the serum.
Persons with a reactive result need to be told that the
preliminary test was positive and that they need a con-
firmatory test. The use of a rapid test should facili-
tate people receiving the results of their HIV test more
regularly because they do not need to return for their
test results 2 weeks later unless it is positive or there is
concern that the person may be in the window period
before seroconversion. The newest development
in HIV testing is a combined antigen-antibody test
(p24 antigen, HIV antibodies), which has the advan-
tage of early detection of HIV, potentially within
2 weeks of infection.
Treatment.
Currently, there is no cure for HIV infec-
tion. The medications that are currently available to
treat HIV infection decrease the amount of virus in the
body, but they do not eradicate HIV.
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The treatment of
HIV infection is one of the most rapidly evolving fields
in medicine.
There currently are five different classes of HIV
antiretroviral medications: nucleoside and nucleotide
analog reverse transcriptase inhibitors; nonnucleoside
reverse transcriptase inhibitors; protease inhibitors;
entry inhibitors; and the newest class, integrase inhibi-
tors. Each class of agents attempts to interrupt the life
cycle of the HIV at different points (see Fig. 16-8).
Reverse transcriptase inhibitors
inhibit HIV replica-
tion by acting on the enzyme reverse transcriptase.
Nucleoside analog reverse transcriptase inhibitors
and
nucleotide reverse transcriptase inhibitors
act by block-
ing the elongation of the DNA chain by stopping more
nucleosides from being added.
Nonnucleoside reverse
transcriptase inhibitors
work by binding to the reverse
transcriptase enzyme so it cannot copy the virus’s RNA
into DNA.
Protease inhibitors
bind to the protease
enzyme and inhibit its action. This inhibition prevents
cleavage of the polypeptide chain into individual pro-
teins, which would be used to construct a new virus.
