Scientific American, 7/98, Catherine M. Wilfert, Ross E. McKinney, page
74
When Children Harbor HIV
HIV Infection is particularly difficult to combat in the young
Children infected with HIV face more obstacles to staying well than adults do. The
virus tends to behave more aggressively in the young, leading more rapidly to the immune
dysfunction of AIDS and to death. Fewer anti-HIV drugs are available for children (those
younger than 13 years), and pediatricians have inadequate childbased data on which to
construct treatment plans. Moreover, the therapeutic strategies thought best from a
medical standpoint can be difficult for families to carry out.
HIV infected children almost always contract the virus from their mothers, during
gestation or through breast-feeding. Roughly two thirds acquire the virus at delivery or
in the days leading up to birth. Worldwide, more than a million children are infected now,
and about 1,500 babies join the afflicted every day, primarily in developing nations.
HIV's aggressiveness in children becomes evident quickly. Infants typically become
symptomatic during the first year of life-much faster than adults, who commonly feel fine
for several years. Similarly, a large fraction of infected babies-up to 16 percent-die
before their fourth birthday because of rapid destruction of the immune system and
development of many of the same opportunistic infections that can fell grown-ups. Very few
adults succumb that quickly.
Beyond becoming sicker more quickly, children can also show effects not observed in older
patients. HIV can invade the young brain early in the disease course. Because this organ
is still immature and evolving in children, the invasion may impair intellectual
development and motor functioning and lead to coordination problems. These effects can be
permanent. Adults may suffer brain dysfunction, too, but usually not until much later
In addition, physical growth may be retarded (both height and weight), even in the absence
of other symptoms. Effective antiviral therapy brings the growth rate back to normal,
however-an observation that allows changes in height and weight to serve as indirect
indicators of whether a treatment plan is controlling the virus.
All children contract more bacterial infections than adults do, simply because they have
not had the years of exposures that build up immunity. When the immune system is depressed
by HIV, vulnerability increases. Consequently, about 20 percent of pediatric AIDS victims
battle serious, recurring bacterial infections, such as meningitis or pneumonia. Some
undergo repeated bouts of viral infections, such as chicken pox, that rarely recur in
their peers.
Scientists now have some sense of why HIV becomes destructive more swiftly in youngsters.
Children often have high viral loads-large concentrations of HIV RNA (viral genes) in
their blood-an indication that the amount of infectious virus in the system is also high.
Adults generally have comparably elevated viral loads soon after contracting HIV, but the
levels drop within months, whereas those in infants remain elevated for years.
Persistently high virus burdens, which can be harder to reduce than small ones, are
associated with faster disease progression and shorter survival.
Treatment Dilemmas
Aside from the inherent challenges of treating patients who harbor large
amounts of HIV in their system, therapy for children can be problematic for other reasons.
Logic suggests that the optimal treatment approaches for adults should work best in
children. In other words, children, like adults, should ideally receive combinations of
three or four different drugs, including one or more from the class known as the protease
inhibitors. (Single anti-HIV drugs have limited value when used on their own, and they
promote viral resistance that undermines the drugs' effectiveness.) Yet this understanding
is difficult to translate into effective action.
Part of the problem is that even in the industrial nations, where health care systems and
medical supplies are extensive, fewer drugs are available for children than for adults.
Because many children cannot swallow pills, they often need liquids or syrups, but certain
anti-HIV compounds are insoluble in water or taste sickening.
Further, drug companies historically have waited to test medications on children until the
agents proved effective in adults. Aside from delaying drug approvals, the paucity of
studies in children has meant that pediatricians frequently resort to guesswork in
choosing drug dosages for children, who must be given amounts calibrated to body size.
Fortunately, the tide is changing. New anti-HIV drugs are being tested more rapidly in
children, and ongoing studies are finally examining three- and four-agent drug regimens
analogous to the aggressive treatment plans of adults.
If the problems of drug availability and dosing were resolved, the intensive regimens
would still be extraordinarily demanding. Three or more agents must be given two or three
times a day, every day, 365 days a year And doses cannot be missed, or HIV can become
resistant to the medications.
Anyone who has had to treat a generally well infant for a simple ear infection knows how
easy it is to forget a dose. Sadly, families of HIV positive children are often less
equipped than most to cope with the stringent demands of intensive anti-HIV therapy. They
may be poor disorganized or headed by a single mother who is ailing herself. Families can
also be reluctant to tell others about a child's HIV status. They may therefore allow
children to skip having medicine at day care or school. Health professionals who treat
these children may thus face the awful task of considering with a family whether
aggressive combination therapy can be handled or whether a less optimal drug regimen
should be used.
Now a new therapeutic quandary has emerged. In the past, treatment for infants was
sometimes delayed for weeks or months after birth. Recent findings in adults suggest,
however, that beginning combination therapy promptly after diagnosis is better for
limiting viral replication and for establishing immunity.
That conclusion in itself is not especially problematic. But the research also implies
that starting powerful therapy immediately at birth - when HIV is usually contracted - can
potentially prevent infection or significantly delay progression to AIDS in infected
infants. Unfortunately, physicians often cannot confirm infection until perhaps two weeks
after delivery, when the virus reaches detectable levels in the blood. To best protect
affected infants, physicians might have to prescribe intensive therapy for all neonates
born to HIV positive women, including for the majority who normally evade HIV infection.
In view of the drawbacks of aggressive anti-HIV therapy complexity, toxicity and expense
many doctors are understandably reluctant to take that course.
Prevention: For Too Few
As always, prevention is the best medicine. The approach used to block
mother-to-infant (vertical) transmission in the industrial nations grew out of a joint
U.S.-French clinical trial called the Pediatric AIDS Clinical Trials Group Protocol 076.
In that landmark 1994 study, HIV infected women took zidovudine (AZT) orally from as early
as the l4th week of pregnancy. During delivery, they were given the drug intravenously.
The newborns were started on zidovudine immediately and kept on it for six weeks. Whereas
26 percent of infants born to untreated mothers acquired HIV infection, only 8 percent of
infants in the treatment group suffered that fate. Neither mothers nor infants showed any
untoward effects from the therapy.
Since 1994, widespread application of the 076 protocol has dramatically reduced
mother-child transmission in the U.S. and parts of Europe.. To protect women as well as
their babies, a group of experts recommends that combination therapy including zidovudine
should be offered to pregnant women, who must, however, be informed of gaps in data on
safety, toxicity and improved efficacy.
Exactly how zidovudine blocks vertical transmission is a mystery. Given alone, the drug
will not lower viral concentrations profoundly. Hence, although women with lower viral
loads are less likely (albeit still able) to pass the virus to their babies, the medicine
is not helping by markedly reducing viral levels in this case. The drug might work
primarily by blocking infection during delivery; when virus-laden maternal secretions can
infect the mucosal surfaces of the infants' eyes, mouth and gastrointestinal tract and
gain access to the bloodstream.
The picture in the developing nations is considerably bleaker than in the U.S. Because
women in those countries typically have limited or no access to prenatal care, the
expensive 076 protocol has not been feasible. A simpler intervention is therefore
essential-ideally consisting of a single dose of medicine at labor to the mother and,
possibly, one to her baby. If the treatment were inexpensive enough, it could be given
without testing for HIV, which would be valuable because in many areas testing is too
expensive or leads to stigmatization. (A woman infected with HIV may be ostracized or
abandoned by her husband if her condition is revealed, even when he is the source of the
disease.)
Studies are under way in the developing world to assess new preventive approaches [see
"Coping with HIV's Ethical Dilemmas," on page 86]. Some involve shorter courses
of zidovudine. Others rely on different drugs.
Earlier this year one of those trials-in Thailand-found that oral zidovudine given for an
average of 25 days at the end of pregnancy and throughout labor and delivery can reduce
the transmission rate by half. Unfortunately, both the reduced course of zidovudine and
the HIV testing that has to precede it are still beyond the grasp of many people.
Physicians who provide care for children or pregnant women infected with HIV continue to
be frustrated by troubling contradictions. Methods proved to limit mother-child
transmission are available but are too complicated and costly for universal use in the
countries with the most pediatric HIV disease. In industrial countries, aggressive
therapeutic regimens akin to those now helping adults could extend life for youngsters,
but many children lack the supports they require for adhering to those treatment programs.
In rich and poor nations alike, the need for simpler approaches to prevention and
treatment is urgent.