The death rates of children with HIV have decreased ninefold
since doctors started prescribing cocktails of antiretroviral drugs
in the mid-1990s, concludes a large-scale study of the long-term
outcomes of children and adolescents with HIV in the United States.
In spite of this improvement, however, young people with HIV continue
to die at 30 times the rate of youth of similar age who do not
have HIV, found researchers from the National Institutes of Health
and other institutions.
Earlier studies have shown that adults with HIV are living longer because of
improved multi-drug antiretroviral regimens known as highly active
antiretroviral therapy (HAART). However, limited information has
existed about the effectiveness of HAART in improving the survival
of children with HIV. The current analysis, published in the Dec.
15 issue of the Journal of Acquired Immune Deficiency Syndromes,
delineates the effects of HAART on the rates and causes of death
for HIV-infected children and adolescents.
Conducted by the Pediatric AIDS Clinical Trials Group, the study was
co-funded by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD) and the National Institute of
Allergy and Infectious Diseases (NIAID), both part of NIH. The study’s
first author is Michael T. Brady, M.D., of Nationwide Children’s
Hospital in Columbus, Ohio.
In 1994, the mortality rate for HIV-infected children and youth
younger than 21 years of age in the United States was 7.2 deaths per
100 person years (a rate based on the number of children in the study
and the total number of years each child was followed). By 2000, that
rate had plummeted to 0.8 deaths per 100 person years and remained
stable through 2006. The mean age at death for HIV-infected youth in
the study more than doubled from 8.9 years in 1994 to 18.2 years in
Although this represents a dramatic improvement in survival, the
death rate for children with HIV is approximately 30 times higher than
that of similarly aged U.S. children who do not have HIV. Multi-organ
failure and kidney disease are now major causes of death for
HIV-infected children and adolescents. Infections also continue to
cause deaths in this group of patients. However, the type of infections
has changed, from infections traditionally associated with AIDS to
infections that are more common in children without HIV infection.
"The findings are very encouraging, but they still show a need for
improvement," said Alan Guttmacher, M.D., acting director of NICHD.
"For both adults and children, combination antiretroviral therapy is
highly effective in preventing the opportunistic infections and other
complications resulting from HIV infection. We must now better
understand and pursue treatments for children and adolescents to
address the other conditions resulting from HIV infection."
"Basic research and clinical studies funded by NIH beginning in the
1980s laid the foundation for the development of the more than two
dozen drugs now available to fight HIV, enabling many children infected
with the virus to live into adulthood,"said NIAID Director Anthony S.
Fauci, M.D. "Now we face the challenge of effectively treating the
consequences of long-term HIV infection in people who have been
infected since childhood."
Between 1993 and 2006, the researchers tracked 3,553 U.S. children
and adolescents infected with HIV. Of those children, 298 died. Growing
numbers of children with HIV began receiving HAART between 1994 and
2000, and death rates declined annually during that period. Nearly 60
percent of all deaths in the study occurred before 1997, before the
advent of HAART for the treatment of children; moreover, children who
died were almost four times as likely to have never received HAART as
those who survived.
"A wonderful change has occurred: Most HIV-infected children now
reach adulthood," said Lynne Mofenson, M.D., an author of the paper and
chief of the Pediatric, Adolescent and Maternal AIDS branch at NICHD.
"Will these children have a normal lifespan? Unfortunately, we don’t
have all the answers yet. Currently, we don’t have the means to prevent
all the complications of HIV infection."
In the early years of the study, secondary infections killed more
than one-third of the children who died, but from 2002 to 2006, that
proportion fell to less than one-fourth. Over time, children and
adolescents with HIV became more likely to die of kidney failure,
stroke, or AIDS-induced multiple organ failure.
To try to prevent these deaths, another long-term study of children
with HIV called the Pediatric HIV/AIDS Cohort Study is being funded by
NICHD, NIAID, the National Institute on Drug Abuse, the National
Institute on Deafness and Other Communication Disorders, the National
Heart, Lung, and Blood Institute, and the National Institute of Mental
Health. This study is monitoring how children and adolescents with the
virus grow and develop, what complications they experience, and whether
they experience side effects from their medication.
"To keep these children healthy, we need to learn more about how HIV
and anti-HIV drugs affect their growing bodies," said Dr. Mofenson. "We
took a big leap in our understanding with this study, and the next
pediatric cohort study will lead to even more improvements in
understanding HIV infection and its treatment in youth."
In addition to Drs. Brady and Mofenson, the other authors of the
article are James M. Oleske, M.D., M.P.H., of the University of
Medicine and Dentistry of New Jersey; Paige L. Williams, Ph.D., of the
Harvard School of Public Health; Carol Elgie of Frontier Science
Technology and Research Foundation; Wayne M. Dankner, M.D., of Parexel
International and Duke University Medical Center, and Russell B. Van
Dyke, M.D., of Tulane University.