ACAPULCO, Mexico When physicians began using zidovudine (ZDV) to prevent maternal transmission of HIV infection, there was a perception in the United States that HIV/AIDS was no longer a pediatric problem.
That perception appears to be a misperception.
"In the United States, we often hear that pediatric HIV/AIDS is such a small problem that it really does not warrant that much research of AIDS in children," said Brigitta Mueller, MD, visiting scientist at the National Institutes of Health. "And it is true in the United States, only 1% of AIDS cases occur in children younger than 13 years. However, on a global scale, 10% of all AIDS cases are children; 1.3 million children have recognized HIV infection.
"In 1996, it's estimated that over 1 million infections occurred, 8,500 infections per day; 1,000 per day in children. These are staggering numbers," added Mueller, who spoke here at the First World Congress of Pediatric Infectious Diseases. Sixty-five percent of these children live in sub-Saharan Africa.
To add to the tragedy, more than 9 million children younger than 15 years have lost their mothers to HIV/AIDS.
In 1996, preliminary data suggested there were about 7,500 U.S. children younger than 13 with AIDS. More than 80% of these are younger than 5 years old. About 90% have vertically acquired disease. And more than 80% are among minorities.
"We as pediatricians often forget about the adolescents," she said, "but also 2,354 adolescents between 13 and 19 years of age; and 18,955 young men and women between the age of 20 and 24 were diagnosed with AIDS. These people were almost certainly infected as young people and adolescents."
The greatest proportion of increases in cases has occurred in women, adolescents and young adults and minorities. Most of the infections in these patient groups have occurred from heterosexual contacts or injecting drug use. Only 2% of adolescent male HIV cases were from heterosexual contact, but more than 50% of female adolescents were infected through heterosexual contact.
Vertical transmission is the most common form of transmission for children, but not all children who are born to HIV-infected mothers become infected. Thirteen percent to 25% will be infected in utero or during delivery; another 10% will be infected through breast feeding.
"We know that transmission does not take place at one single moment in time. About one-third of vertical transmissions will occur during pregnancy; most cases will occur during the birth process and some during breast feeding, especially in developing countries, where breast milk is still safer than using the water to make formula," she said.
There has been a lot of discussion trying to determine what is a risk factor for maternal transmission; maternal viral load and CD4 counts probably play a role as does the duration of the delivery, she said.
Although pediatric AIDS is still a U.S. problem, the information provided from ACTG 076 was a "high point" in pediatric AIDS research, Mueller said. ACTG 076 was the study that found that the risk of maternal-fetal transmission could be reduced if ZDV was given during pregnancy.
The regimen calls for women to receive oral ZDV while pregnant, then IV ZDV during delivery; and for the baby to receive oral ZDV for six weeks after birth. The regimen was found to be well-tolerated by both mothers and children. However, it is a complicated regimen for people in developing countries to follow. "A lot more has to be done to ease the regimen," she said.
The infection progresses differently in children than adults. Children usually have a more rapid course. About one-third will be in the rapid progressor group. These children become sick within the first four months of life, often associated with a dramatic decrease in CD4 counts. It is likely that these are the children who became infected during pregnancy, according to Mueller.
Most children with HIV fall into an intermediate group. They become symptomatic within the first few years of life.
"Fortunately, there is also a growing group of children who follow an adult equivalent. They become symptomatic within eight to 10 years," she said.
CD4 counts are age-dependent. Young children have high CD4 counts. Therefore, a young child with CD4 counts under 750 is considered severely immunocompromised. For older children, cell counts have to fall below 200 cells before they are considered severely immunocompromised.
Viral load also shows itself differently in children. When adults become infected, they have an initial peak that then comes down rapidly and stays down for many years until the patient progresses to AIDS and then the viral load starts to increase again. Most children, however, have high initial viral loads. Most children are in the 500,000 copies/ml range. In comparison, adults are in the 50,000 copies/ml range.
"If children don't get treated, the viral load stay up in that range for years, so it is not just an initial peak as has been described in adults. Children's viral loads stay up there for up to three years, and very slowly come down," she said.
Baseline HIV RNA was predictive of AIDS progression in adults but what that means for a child is uncertain. "In children, the data are just emerging; we are trying to make sense out of the data we have. There is a difference between symptomatic and asymptomatic children. Rapid progressors showed earlier and greater increase in viral load than slow progressors, concurrent with a decrease in CD4 counts."
Mueller said that viral load measurements are important for both individual patients and for the rapid development of new therapies, and they should be incorporated into patient management. But do not base treatment decisions on viral load alone. "Other measurements like CD4 counts, weight loss and clinical progression should not be forgotten or put aside. They are important," she said.
Mueller said more information about the disease in children is needed to better understand the risk factors for transmission as well as progression. "To prevent maternal transmission, [we need] regimens that are feasible for developing countries, vaccines for prophylaxis and vaccines to preserve the immune system," she said.
In addition, more affordable antiretroviral agents that are simple to store and administer are needed. Combination formulations of antiretroviral agents would also be helpful, she said.
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