C h a p t e r 1 6
Disorders of the Immune Response
371
Two new classes of antiretroviral therapy are the
entry
inhibitors
and
integrase inhibitors.
The entry inhibitors
prevent HIV from entering or fusing with the CD4
+
cell, thus blocking the virus from inserting its genetic
information into the CD4
+
T cell. The integrase inhibi-
tors block the integration step of the viral cycle, thus
preventing the HIV genome from integrating into the
host’s genome.
Because different drugs act at different stages of the
replication cycle, optimal treatment includes a combina-
tion of at least three antiretroviral drugs, referred to as
highly active antiretroviral therapy
(HAART). The goal
of HAART is a sustained suppression of HIV replica-
tion, resulting in an undetectable viral load and increas-
ing CD4
+
cell count. In general, antiviral therapies are
prescribed to slow the progression of AIDS and improve
the overall quality of life and survival time of persons
with HIV infection.
Preventive and therapeutic vaccines for HIV are also
being investigated.
80
The preventive vaccine would be
given to someone who is HIV negative, with the goal of
preventing infection if exposed to HIV. The therapeutic
vaccine would be used in people who are already infected
with HIV as a way to control HIV replication. In trials
to date, these vaccines have not proven beneficial.
A new preventive strategy has been approved by the
FDA in the United States. PrEP—pre-exposure prophy-
laxis—involves consistently taking antiretroviral medi-
cation that may interrupt infection if exposed to HIV
in high-risk settings. It is not 100% effective at prevent-
ing HIV infection; routine counseling on reducing risky
behaviors and routine evaluations for sexually transmit-
ted infections are still paramount. Individuals taking
PrEP also need to be routinely monitored for efficacy
and side effects of the medication.
HIV Infection in Pregnancy and in Infants
and Children
Transmission from mother to infant is the most com-
mon way that children become infected with HIV.
Human immunodeficiency virus may be transmitted
from infected women to their offspring in utero, dur-
ing labor and delivery, or through breast-feeding.
81
Most transmissions from mother to child occur during
childbirth when the mother’s infected blood in the birth
canal infects the baby. Breast-feeding, particularly in
poor countries, can account for one third to one half
of all mother-to-child transmission. Screening programs
for pregnant women and antiretroviral prophylaxis are
available for preventing mother-to-child transmission in
HIV-positive women. Epidemiologic estimates suggest
that coverage for antiviral prophylaxis to HIV-positive
women for prevention of mother-to-child transmis-
sion in low- to middle-income countries increased from
9% in 2004 to 33% in 2007 to 57% in 2011.
44,47
Diagnosis and Treatment.
Diagnosis of HIV infection
in children born to HIV-infected mothers is complicated
by the presence of maternal anti-HIV IgG antibody,
which crosses the placenta to the fetus.
82
Consequently,
infants born to HIV-infected women can be HIV anti-
body positive by ELISA up until 18 months of age even
though they are not infected with HIV. Polymerase
chain reaction testing for HIV DNA is used most often
to diagnose HIV infection in infants younger than 18
months of age. Two positive PCR tests are needed for
diagnosis. Children born to mothers with HIV infection
are considered uninfected if they become HIV antibody
negative after 18 months of age, have no other labora-
tory evidence of HIV infection, and have not met the
case definition criteria for AIDS in children.
The landmark Pediatric AIDS Clinical Trials Group
(PACTG) 076 study reported that perinatal transmis-
sion could be lowered by two-thirds, from 26% to 8%,
by administering zidovudine to the mother during preg-
nancy and labor and delivery and to the infant when
it is born.
83
The U.S. Public Health Service therefore
recommends that HIV counseling and testing should
be offered to all pregnant women.
84
The recommen-
dations also stress that women who test positive for
HIV antibodies should be informed of the perinatal
prevention benefits of zidovudine therapy and offered
HAART, which often includes zidovudine. This is
done because it has been found that women receiving
antiretroviral therapy who also have a viral load less
than 1000 copies/mL have very low rates of perinatal
transmission. Efavirenz, a non-nucleoside reverse tran-
scriptase inhibitor, has the potential for causing neural
tube defects within the first 6 weeks of pregnancy. HIV-
infected women of child-bearing age should be tested
for pregnancy and counseled regarding the potential
adverse effects prior to initiating HAART with efavi-
renz. If a woman is taking an efavirenz-based regimen
and pregnancy is determined after 6 weeks, then she
may continue the regimen as long as virologic suppres-
sion is maintained and the pregnancy is monitored.
79
Benefits of voluntary testing for mothers and newborns
include reduced morbidity because of intensive treat-
ment and supportive health care, the opportunity for
early antiretroviral therapy for mother and child, and
information regarding the risk of transmission from
breast milk.
Clinical Manifestations.
Children may have a differ-
ent clinical presentation of HIV infection than adults.
82
Failure to thrive, CNS abnormalities, and developmen-
tal delays are the most prominent primary manifesta-
tions of HIV infection in children. Children born with
HIV infection usually weigh less and are shorter than
noninfected infants. A major cause of early mortality for
HIV-infected children is
P. jiroveci
pneumonia, which
occurs early in children, with the peak age of onset at
3 to 6 months. For this reason, prophylaxis with tri-
methoprim-sulfamethoxazole should be started begin-
ning at 4 to 6 weeks for all infants born to HIV-infected
mothers, regardless of their CD4
+
cell count or infection
status.
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