Page 399 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART IV Clinical Virology
388
increases. The long-term effect of this approach on rate of
them into a test strain of HIV, which is then used to infect
progression to AIDS has yet to be determined.
Pregnant women infected with HIV should be treated
cells in culture. Another laboratory test can determine the
tropism of the patient’s isolate (i.e., whether it uses CCR5 as
with two nucleosides and a protease inhibitor. A typical
regimen would include lamivudine, ZDV, and lopinavir/
its coreceptor). If so, then maraviroc can be used for
ritonavir. In addition, ZDV should be given to the neonate.
These drugs appear not to damage the fetus, although rare
instances of mitochondrial dysfunction and death attrib-
Immune Reconstitution Inflammatory Syndrome
uted to ZDV have been reported. The reader is urged to treatment.
Immune reconstitution inflammatory syndrome (IRIS)
consult the current information regarding the use of these
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may occur in HIV-infected patients who are treated with
drugs in pregnancy. A full discussion is beyond the scope
a HAART regimen and who are coinfected with other
of this book.
microbes such as HBV, HCV, M. tuberculosis, M. avium
Entry Inhibitors
gondii. In this syndrome, an exacerbation of clinical
symptoms occurs because the antiretroviral drugs
Table 45–3 describes two entry inhibitors, enfuvirtide and
enhance the ability to mount an inflammatory response.
maraviroc. Enfuvirtide (Fuzeon) is the first of a new class
of anti-HIV drugs known as fusion inhibitors (i.e., they
HIV-infected patients with a low CD4 count have a
prevent the fusion of the viral envelope with the cell mem-
reduced capacity to produce inflammation, but HAART
brane). Enfuvirtide is a synthetic peptide that binds to gp41
symptoms become more pronounced. To avoid IRIS, the
on the viral envelope, thereby blocking the entry of HIV
coinfection should be treated prior to instituting HAART
into the cell. It must be administered by injection and is
whenever possible.
quite expensive. restores the inflammatory response, and as a result,
Maraviroc (Selzentry) also prevents the entry of HIV
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into cells. It blocks the binding of the gp120 envelope
Prevention
protein of HIV to CCR-5, which is an important corecep-
tor on the cell surface. Before prescribing maraviroc, a
experimental vaccines have failed to induce protective
laboratory test (Trofile assay) should be performed to
antibodies, protective cytotoxic T cells, or mucosal immu-
ensure that the tropism of the patient’s strain of HIV is
nity. Prevention consists of taking measures to avoid
CCR5. Maraviroc should be used in combination with
exposure to the virus (e.g., using condoms, not sharing
other antiretroviral drugs in patients infected with CCR5-
needles, and discarding donated blood that is contami-
tropic strains of HIV and in treatment-experienced adults
nated with HIV).
infected with an HIV strain that is resistant to other anti-
Postexposure prophylaxis (PEP), such as that given
retroviral drugs.
exposure, employs three drugs: the preferred regimen con-
Integrase Inhibitors after a needle-stick injury or a high-risk nonoccupational
sists of the combination of tenofovir and emtricitabine
Raltegravir (Isentress) is the first drug to inhibit the
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(given as Truvada) plus raltegravir. Three alternative drug
HIV-encoded integrase (see Table 45–3). It is recom-
regimens are available. PEP should be given as soon as pos-
mended for use in patients who have been treated with
other antiretroviral drugs but continue to produce sig-
also be used for preexposure prophylaxis (PrEP) in indi-
nificant levels of HIV. Two additional integrase inhibi-
viduals at high risk of infection, such as men who have sex
tors are available: dolutegravir (Tivicay) and elvitegravir
with men.
(Stribild).
Two steps can be taken to reduce the number of cases of
HIV infection in children: antiretroviral therapy should be
Resistance to Antiretroviral Drugs
given to HIV-infected mothers and neonates, and HIV-
Drug-resistant mutants of HIV have emerged that signifi-
cantly affect the ability of both reverse transcriptase inhibi-
antiretroviral drugs is dependent on several factors, so cur-
tors and protease inhibitors to sustain their clinical efficacy.
rent guidelines should be consulted. In addition, the risk of
neonatal HIV infection is lower if delivery is accomplished
Approximately 10% of newly infected patients are infected infected mothers should not breast feed. The choice of
with a strain of HIV resistant to at least one antiretroviral
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by cesarean section rather than by vaginal delivery. Cir-
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drug. Laboratory tests to detect mutant strains include both
cumcision reduces HIV infection.
Several drugs are commonly taken by patients in the
genotypic and phenotypic analysis. Genotyping reveals the
presence of specific mutations in either the reverse tran-
infections (Table 45–4). Some examples are trimethoprim-
scriptase (RT) or protease (PR) genes. Phenotyping deter-
sulfamethoxazole to prevent Pneumocystis pneumonia, flu-
mines the ability of the virus to grow in cell culture in the
presence of the drug. One method of phenotyping recovers
conazole to prevent recurrences of cryptococcal meningitis,
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