Research for Child HIVers Needed

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.

Despite 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, according to researchers from the National Institutes of Health and other institutions.

Earlier studies have shown that adults with HIV are living longer because of improved multidrug antiretroviral regimens known as highly active antiretroviral therapy. However, limited information has existed about the effectiveness of HAART in improving the survival of children with HIV. The current analysis, published in the December 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 cofunded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Allergy and Infectious Diseases, both part of NIH. The study's first author is Michael T. Brady, MD, 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 2006.

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. Multiple 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," says Alan Guttmacher, MD, 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, MD. "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," says Lynne Mofenson, MD, 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," says 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."