HIV In Infants and Children

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HIV Infection in Infants and Children

The
National Institute of Allergy and Infectious Diseases (NIAID) has a lead
role in research devoted to children infected with HIV (human
immunodeficiency virus), the virus that causes AIDS (acquired
immunodeficiency syndrome). NIAID-supported researchers are developing
and refining treatments to prolong the survival and improve the quality
of life of HIV-infected infants and children through the Pediatric AIDS
Clinical Trials Group (PACTG). The PACTG is a nationwide clinical trials
network jointly sponsored by NIAID and the National Institute of Child
Health and Human Development (NICHD). NIAID also supports research on
ways to prevent mother-to-child transmission (MTCT) of HIV through the
PACTG and its HIV Prevention Trials Network (HPTN), a global clinical
trials network designed to test promising nonvaccine strategies to
prevent the spread of HIV/AIDS.

In this era of antiretroviral therapy, epidemiologic studies such as
NIAID’s Women and Infant’s Transmission Study (WITS) are examining risk
factors for transmission as well as the course of HIV disease in
pregnant women and their babies. Researchers have helped illuminate the
mechanisms of HIV transmission, the distinct features of pediatric HIV
infection, and how the course of disease and the usefulness of therapies
can differ in children and adults.

A GLOBAL PROBLEM

According to UNAIDS (The Joint United
Nations Programme on HIV/AIDS) at the end of 2003, an estimated 2.5
million children worldwide under age 15 were living with HIV/AIDS.
Approximately 500,000 children under 15 had died from the virus or
associated causes in that year alone. As HIV infection rates rise in the
general population, new infections are increasingly concentrating in
younger age groups.

December 2003 UNAIDS/World Health Organization (WHO) worldwide statistics show

  • 700,000 children under age 15 were newly infected with HIV
  • Thirteen percent of all new HIV infections were in children under age 15
  • Three million children in sub-Saharan Africa, the region with the highest number of cases, are living with HIV

More than 95 percent of all HIV-infected people now live in
developing countries, which have also suffered 95 percent of all deaths
from AIDS. In those countries with the highest prevalence, UNAIDS
predicts that, between 2000 and 2020, 68 million people will die
prematurely as a result of AIDS. In seven sub-Saharan African countries,
mortality due to HIV/AIDS in children under age five has increased by
20 to 40 percent. Life expectancy for a child born in Botswana, the
country with the highest HIV prevalence in the world, has dropped below
40 years-a level not seen in that country since before 1950.

The United States has a relatively small percentage of the
world’s children living with HIV/AIDS. From the beginning of the
epidemic through the end of 2002, 9,300 American children under age 13
had been reported to the Centers for Disease Control and Prevention
(CDC) as living with HIV/AIDS. The vast majority of HIV-infected
children acquire the virus from their mothers before or during birth or
through breast feeding. Because of the widespread use of AZT and other
highly active antiretroviral therapy (HAART) in HIV-infected pregnant
women in the United States, only 92 new cases of pediatric AIDS were
reported in 2002. More than three times that number are infected with
HIV but have not yet developed AIDS.

  • The U.S. city with the highest rate of pediatric AIDS through
    2002 was New York City, followed by Miami, FL, and Washington, DC.
  • The disease disproportionately affects children in minority
    groups, especially African Americans. Out of 9,300 cases in children
    under 13 reported to the CDC through December 2002, 59 percent were
    black/non-Hispanic, 23 percent were Hispanic, 17 percent were
    white/non-Hispanic, and less than 1 percent were in other minority
    groups.

New anti-HIV drug therapies and promotion of voluntary testing
continue to positively effect the death rate. CDC reported a drop of 68
percent from 1998 to 2002 in the estimated number of children who died
from AIDS.

TRANSMISSION

Almost all HIV-infected children acquire the
virus from their mothers before or during birth or through
breastfeeding. In the United States, approximately 25 percent of
pregnant HIV-infected women not receiving AZT therapy have passed on the
virus to their babies. The rate is significantly higher in developing
countries.

Prior to 1985 when screening of the nation’s blood supply for HIV
began, some children as well as adults 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.

PREGNANCY AND BIRTH

Most MTCT, estimated to cause
more than 90 percent of infections worldwide in infants and 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 MTCT 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 are maternal drug use,
severe inflammation of fetal membranes, or a prolonged period between
membrane rupture and delivery. A study sponsored by NIAID and others
found that HIV-infected women who gave birth more than 4 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 4 hours
of membrane rupture.

BREASTFEEDING

HIV also may be transmitted from a
nursing mother to her infant. Studies have suggested that breastfeeding
introduces an additional risk of HIV transmission of approximately 10 to
14 percent among women with chronic HIV infection. In developing
countries, an estimated one-third to one-half of all HIV infections are
transmitted through breastfeeding.

WHO recommends that all HIV-infected women be advised about both the
risks and benefits of breastfeeding for their infants so they can make
informed decisions. In countries where safe alternatives to
breastfeeding are readily available and economically feasible, this
alternative should be encouraged. In general, in developing countries
where safe alternatives to breastfeeding are not readily available, the
benefits of breastfeeding in terms of decreased illness and death due to
other infectious diseases greatly outweigh the potential risk of HIV
transmission.

PREVENTING MOTHER-TO-CHILD TRANSMISSION

In 1994, a landmark
study conducted by the PACTG 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 MTCT by two-thirds, from 25 percent to 8 percent. In the study,
AZT therapy was initiated in the second or third trimester and continued
during labor, and infants were treated for 6 weeks following birth. AZT
produced no serious side effects in mothers or infants. Long-term
follow up of the infants and mothers is ongoing.

A few years later, another PACTG study found that the risk of
transmitting HIV from an HIV-positive mother to her newborn infant could
be reduced to 1.5 percent in those women who received antiretroviral
treatment and appropriate medical and obstetrical care during pregnancy.

Combination therapies have been shown to be beneficial in treating HIV-infected adults, and current guidelines have

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