Go to the Women & Children Menu
4-307
Return to the
Pediatric
AIDS Menu
Overview
The National Institute
of Allergy and Infectious Diseases (NIAID)
has a lead role in research devoted to
children infected with the human
immunodeficiency virus (HIV), the virus that
causes the acquired immunodeficiency syndrome
(AIDS). NIAID-supported
researchers are developing and refining
treatments to prolong the survival and
improve the quality of life of HIV-infected
infants, children and adolescents. Many
promising therapies are being tested in the
Pediatric AIDS Clinical Trials Group (ACTG),
a nationwide clinical trials network jointly
sponsored by NIAID and the National Institute
of Child Health and Human Development
(NICHD). Scientists also are improving tests
for diagnosing HIV infection in infants soon
after birth so that therapy can begin as soon
as possible. Epidemiologic studies
are examining risk factors for transmission
as well as the course of HIV disease in
pregnant women and their babies in an era of
antiretroviral therapy. Researchers have
helped illuminate the mechanisms of HIV
transmission as well as the distinct features
of pediatric HIV infection and how the course
of disease and the usefulness of therapies
can differ in children and adults. Researchers also are
studying ways to prevent transmission of HIV
from mother to infant. Notably, Pediatric
ACTG investigators have demonstrated that a
specific regimen of zidovudine (AZT)
treatment, given to an HIV-infected woman
during pregnancy and to her baby after birth,
can reduce maternal transmission of HIV by
two-thirds. Many consider this finding to be
one of the most significant research advances
to date in the fight against HIV and AIDS.
Return to the
Pediatric
AIDS Menu
The Scope of the Problem
UNAIDS and the World
Health Organization (WHO) estimate that by
late 1996, 2.6 million children worldwide had
been infected with HIV and 1.3 million had
died as a result. By 2000, the WHO projects
that 5 to 10 million children will have been
infected with HIV, with another 5 to 10
million children orphaned by the HIV/AIDS
pandemic. In the United States,
through December 1996, 7,629 cases of AIDS in
children younger than 13 and 2,754 cases in
those aged 13 through 19 had been reported to
the Centers for Disease Control and
Prevention (CDC). Many other children are
currently infected with HIV but have not yet
developed AIDS. HIV infection ranks
seventh among the leading causes of death for
U.S. children 1 to 14 years of age. In many
cities in the northeastern United States, HIV
disease is the leading cause of death among
children ages 2 to 5.
Return to the
Pediatric
AIDS Menu
Transmission
Almost all HIV-infected
children acquire the virus from their mothers
before or during birth, a process called
perinatal
transmission. In the United States,
approximately 25 percent of pregnant
HIV-infected women not receiving AZT therapy
have passed on the virus to their
babies. Most perinatal
transmission, causing an estimated 50 to 80
percent of infections in children, probably
occurs late in pregnancy or during birth.
Although the precise mechanisms are unknown,
scientists think HIV may be transmitted when
maternal blood enters the fetal circulation,
or by mucosal exposure to virus during labor
and delivery. The role of the placenta in
maternal-fetal transmission is unclear and
the focus of ongoing research. The risk of perinatal
transmission is significantly increased if
the mother has advanced HIV disease,
increased levels of HIV in her bloodstream,
or fewer numbers of the immune system cells
-- CD4+ T cells -- that are the main targets
of HIV. Other factors that may
increase the risk of perinatal transmission
are maternal drug use, severe inflammation of
fetal membranes, or a prolonged period
between membrane rupture and delivery. A
recent study sponsored by NIAID and others
found that HIV-infected women who gave birth
more than four hours after the rupture of the
fetal membranes were nearly twice as likely
to transmit HIV to their infants, as compared
to women who delivered within four hours of
membrane rupture. HIV also may be
transmitted from a nursing mother to her
infant. Recent studies suggest that
breast-feeding introduces an additional risk
of HIV transmission of approximately 14
percent among women with chronic HIV
infection. The WHO recommends that all
HIV-infected women be advised as to both the
risks and benefits of breast-feeding of their
infants so that they can make informed
decisions. In countries where safe
alternatives to breast-feeding are readily
available and economically feasible, this
alternative should be encouraged. In general,
in developing countries where safe
alternatives to breast-feeding are not
readily available, the benefits of
breast-feeding in terms of decreased illness
and death due to other infectious diseases
greatly outweigh the potential risk of HIV
transmission. Prior to 1985 when
screening of the nation's blood supply for
HIV began, some children were infected
through transfusions with blood or blood
products contaminated with HIV. A small
number of children also have been infected
through sexual or physical abuse by
HIV-infected adults.
Return to the
Pediatric
AIDS Menu
Preventing Perinatal HIV Transmission
In 1994, a landmark
study conducted by the Pediatric ACTG
demonstrated that AZT, given to HIV-infected
women who had very little or no prior
antiretroviral therapy and CD4+ T cell counts
above 200/mm3, reduced the risk of
maternal-infant transmission by two-thirds,
from 25 percent to 8 percent. In the study, known as
ACTG 076, AZT therapy was initiated in the
second or third trimester and continued
during labor, and infants were treated for
six weeks following birth. AZT produced no
serious side effects in mothers or infants;
long-term follow-up of the infants and
mothers is ongoing. Researchers have
subsequently shown that this AZT regimen has
reduced perinatal transmission in other
populations in which it has been used.
Several recent observational studies in the
United States and Europe indicate that
similar reductions in perinatal HIV
transmission can be achieved by using this
regimen in regular clinical care
settings. Following up on the
success of ACTG 076, the Pediatric ACTG has
begun new perinatal HIV prevention trials
that build on the AZT regimen. These trials
include additional antiretrovirals in an
attempt to reduce perinatal HIV transmission
even more than that achieved by AZT
alone. The AZT regimen used in
ACTG 076 is not always available because of
cost and logistical demands. Therefore, NIAID
is pursuing a global strategy that assesses
whether simpler and less costly regimens for
preventing mother-to-infant HIV transmission
can be effective in various settings. Because a significant
amount of perinatal HIV transmission occurs
around the time of birth, and the risk of
maternal-fetal transmission depends, in part,
on the amount of HIV in the mother's blood,
it may be possible to reduce transmission
using drug therapy only around the time of
birth. NIAID has planned other
studies that will assess the effectiveness of
this approach as well as the role of new
antiretrovirals, microbicides and other
innovative strategies in reducing the risk of
perinatal transmission.
Return to the
Pediatric
AIDS Menu
Diagnosis
HIV infection is often
difficult to diagnose in very young children.
Infected babies, especially in the first few
months of life, often appear normal and may
exhibit no telltale signs that would allow a
definitive diagnosis of HIV infection.
Moreover, all children born to infected
mothers have antibodies to HIV, made by the
mother's immune system, that cross the
placenta to the baby's bloodstream before
birth and persist for up to 18 months.
Because these maternal antibodies reflect the
mothers but not the infants
infection status, the test is not useful in
newborns or young infants. In the past few years,
investigators have demonstrated the utility
of highly accurate blood tests in diagnosing
HIV infection in children 6 months of age and
younger. One laboratory technique called
polymerase chain reaction (PCR) can detect
minute quantities of the virus in an infant's
blood. Another procedure allows physicians to
culture a sample of an infant's blood and
test it for the presence of HIV. Currently, PCR assays
or HIV culture techniques can identify at
birth about one-third of infants who are
truly HIV-infected. With these techniques,
approximately 90 percent of HIV-infected
infants are identifiable by 2 months of age,
and 95 percent by 3 months of age. One
innovative new approach to both RNA and DNA
PCR testing uses dried blood spot specimens,
which should make it much simpler to gather
and store specimens in field settings.
Return to the
Pediatric
AIDS Menu
Progression of HIV Disease in Children
Researchers have
observed two general patterns of illness in
HIV-infected children. About 20 percent of
children develop serious disease in the first
year of life; most of these children die by
age 4 years. The remaining 80
percent of infected children have a slower
rate of disease progression, many not
developing the most serious symptoms of AIDS
until school entry or even adolescence. A recent report from a
large European registry of HIV-infected
children indicated that half of the children
with perinatally acquired HIV disease were
alive at age 9. Another study, of 42
perinatally HIV-infected children who
survived beyond 9 years of age, found about
one-quarter of the children to be
asymptomatic with relatively intact immune
systems. The factors responsible
for the wide variation observed in the rate
of disease progression in HIV-infected
children are a major focus of the NIAID
pediatric AIDS research effort. The Women and
Infants Transmission Study, a multisite
perinatal HIV study funded by NIH, has found
that maternal factors including Vitamin A
level and CD4 counts during pregnancy, as
well as infant viral load and CD4 counts in
the first several months of life, can help
identify those infants at risk for rapid
disease progression who may benefit from
early aggressive therapy.
Return to the
Pediatric
AIDS Menu
Signs and Symptoms of Pediatric HIV Disease
Many children with HIV
infection do not gain weight or grow
normally. HIV-infected children frequently
are slow to reach important milestones in
motor skills and mental development such as
crawling, walking and speaking. As the
disease progresses, many children develop
neurologic problems such as difficulty
walking, poor school performance, seizures,
mental retardation and cerebral palsy. Like adults with HIV
infection, children with HIV develop
life-threatening opportunistic infections
(OIs), although the incidence of various OIs
differs in adults and children. For example,
toxoplasmosis is seen less frequently in
HIV-infected children than in HIV-infected
adults, while serious bacterial infections
occur more commonly in children than in
adults. Also, as children with HIV become
sicker, they may suffer from chronic diarrhea
due to opportunistic pathogens. Pneumocystis carinii
pneumonia (PCP) is the leading cause of death
in HIV-infected children with AIDS. PCP, as
well as cytomegalovirus (CMV) disease,
usually are new infections in children,
whereas in adults these diseases result from
the reactivation of latent infections. A lung disease called
lymphocytic interstitial pneumonitis (LIP),
rarely seen in adults, also occurs frequently
in HIV-infected children. This condition,
like PCP, can make breathing progressively
more difficult and often results in
hospitalization. Children with HIV
suffer the usual childhood bacterial
infections -- only more frequently and more
severely than uninfected children. These
bacterial infections can cause seizures,
fever, pneumonia, recurrent colds, diarrhea,
dehydration and other problems that often
result in extended hospital stays and
nutritional problems. HIV-infected children
frequently have severe candidiasis, a yeast
infection that can cause unrelenting diaper
rash and infections in the mouth and throat
that make eating difficult.
Return to the
Pediatric
AIDS Menu
Treatment of HIV-Infected Children
Anti-HIV Therapies.
NIAID investigators are defining the best
treatments for pediatric patients. Largely
due to studies in the Pediatric ACTG, four
anti-HIV agents are currently approved for
use in children. In addition, two protease
inhibitors are now approved for children with
HIV disease. Most doctors consider giving
anti-HIV therapy to children who have
HIV-related symptoms or who have laboratory
evidence of immunosuppression. NIAID-supported
researchers have demonstrated that two
treatment regimens -- ddI alone or in
combination with AZT -- are each superior to
AZT alone in children who have had little or
no previous antiretroviral therapy. Many
other promising new antiretroviral regimens
are being assessed for use in children in the
Pediatric ACTG, including various
combinations of nevirapine, d4T, lamivudine
(3TC), and 1592U89. The Institute also is
undertaking clinical trials of new protease
inhibitors in pediatric patients, as well as
novel treatment approaches such as gene
therapy. The overall trend in both adult and
pediatric HIV disease management is for early
and aggressive use of combination
antiretroviral therapy to keep HIV virus
replication at as low a level as possible.
Opportunistic
Infections. Many medications used to
treat adults with opportunistic infections
are effective in children when given in
appropriate doses. For example, 85 percent of
HIV-infected children are able to tolerate
trimethoprim-sulfamethoxazole (TMP/SMX) for
PCP. This drug is extremely effective in
preventing new or recurrent PCP in children
and is the first choice for pediatric
patients, as it is in adult patients. NIAID
studies are assessing alternative treatments
to prevent PCP in children who do not benefit
from or cannot tolerate TMP/SMX. NIAID investigators are
developing pediatric formulations of other
agents commonly used against OIs, and to
understand how children absorb and metabolize
these drugs. Immune Product
Studies. Clinical trials sponsored by
NIAID and NICHD have demonstrated that
intravenous immunoglobulin (IVIG), a
preparation containing many types of
antibodies, can reduce bacterial infections
frequent in children with AIDS. However, the
NIAID study suggested that the benefits of
IVIG are confined to those patients who had
not received TMP/SMX as preventive therapy
for PCP. Studies are now underway to assess
whether specially made immune globulin
products with extra antibodies to HIV can
further improve the health status of children
with HIV.
Return to the
Pediatric
AIDS Menu
AIDS in Adolescents
Adolescents account for
a rapidly growing percentage of the reported
AIDS cases in the United States. Although
less than 1 percent of AIDS patients in the
United States are between 13 and 19 years of
age, this figure underestimates the
significance of HIV transmission during
adolescence. Since the average
period of time from HIV infection to the
development of AIDS is 10 years, the majority
of people in their twenties with AIDS were
likely infected as adolescents. Approximately
20 percent of all reported cases of AIDS in
the United States have occurred in young
adults between the ages of 20 and 29. Several recent studies
have found that increasing numbers of
teenagers are becoming infected with HIV,
especially in poor, urban areas as well as in
rural areas of the South. Surveys of military
recruits and Job Corps participants as well
as blinded seroprevalance studies indicate
that as many as one in 20 individuals aged 15
to 20 years from certain populations in the
northeastern and southern United States are
HIV-infected.
Return to the
Pediatric
AIDS Menu
Psychosocial Issues
A disproportionate
number of children with AIDS belong to
minority groups: 84 percent of children
reported with AIDS in 1996 in the United
States were black or Hispanic. Most live in
inner cities, where poverty, illicit drug
use, poor housing and limited access to and
use of medical care and social services add
to the challenges of HIV disease. A mother
and child with HIV usually are not the only
family members with the disease. Often, the
mother's sexual partner is infected, and
other children in the family may be infected
as well. Frequently, a mother with AIDS does
not survive to care for her HIV-infected
child. Management of the
complex medical and social problems of
families affected by HIV requires a
multidisciplinary case management team,
integrating medical, social, mental health
and educational services. NIAID provides
special funding to many of its clinical
research sites to provide for services, such
as transportation, day care, and the
expertise of social workers, crucial to
families devastated by HIV.
Return to the
Pediatric
AIDS Menu
Resources
AIDS Clinical Trials
Information Service. For information
about pediatric and adult AIDS clinical
trials open to enrollment, call (800)
TRIALS-A, 9 a.m. to 7 p.m. Eastern Time,
Monday through Friday. National AIDS
Hotline. Staffed 24 hours a day, seven
days a week. (800) 342-AIDS. The National
Pediatric HIV Resource Center. (800)
362-0071. The Pediatric AIDS
Foundation. (415) 883-1796. The Pediatric Branch
of the National Cancer Institute conducts
clinical trials for HIV-infected children on
the NIH campus in Bethesda, Md. (301)
402-0696.
Go to the Women & Children
Menu Go to the HIVpositive.us Main
Menu
4-307
39