HIV Infected: Face New Challenges
NANCY WALSH (New York Bureau)
BOSTON — The increased survival among HIV-infected children seen with effective prevention of perinatal transmission and the widespread adoption of highly-active antiretroviral therapy has been accompanied by the emergence of a new generation of clinical, public health, and social challenges.
The median age of more than 3,500 infected children followed at U.S. clinical trial sites is now 15 years, and some patients are in their early 20s. The median age at death—9 years in 1994—had risen to 18 years by 2006, said Dr. Lynne Mofenson, chief of the Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md.
Although mortality has decreased, it remains 30 times higher for HIV-infected children than for uninfected children. There also has been a shift in causes of death, with fewer children dying from AIDS-related opportunistic infections and central nervous system disease and more succumbing to end-stage AIDS with multiple organ failure, or to sepsis or renal failure, Dr. Mofenson said at the 15th Conference on Retroviruses and Opportunistic Infections.
Aside from the disease itself, these young patients and their caregivers today face multiple challenges including drug resistance, complications of therapy, and issues related to adherence and mental health, Dr. Mofenson said.
Several studies have found an increase in primary drug resistance among newly infected infants. For instance, data from New York State showed a 58% increase in resistance between 1998 and 2002, reaching 19%. This was primarily accounted for by mutations conferring resistance to the nonnucleoside reverse transcriptase inhibitors (J. Acquir. Immune Defic. Syndr. 2006;42:614–9).
Another series found resistance among 24% of infected children, with 10% being resistant to at least two classes of antiretroviral drugs, Dr. Mofenson said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.
Multidrug resistance is a particular problem for older children who were treated with monotherapy or dual therapy before triple therapy became the standard of care. Few choices remain for these children, particularly because many drugs available for adult patients have no pediatric formulations or dosing guidelines. “Without additional drugs, some HIV-infected children will run out of treatment options,” she said.
Investigations by the Pediatric Spectrum of Disease Project found that in 2001, 44% of children had already received two or more highly-active antiretroviral treatment (HAART) regimens, and 3% had received five or more regimens. “This is only going to increase over time,” she said.
These children increasingly face potentially severe complications of long-term therapy, particularly during puberty when as-yet unidentified physiologic changes appear to result in the development of hypercholesterolemia, which has been reported in up to 67% of children on therapy, and lipodystrophy, which has been reported in up to 47%.
Additionally, in one series, hyperinsulinemia was found in 60% of children, although insulin resistance was uncommon, she said.
Risk factors that have been identified for the development of these metabolic abnormalities include duration of antiretroviral therapy and the use of protease inhibitors and nucleoside reverse transcriptase inhibitors.
In one study from England, carotid intima thickness was significantly greater among 83 HIV-infected children, compared with a control group of 59 healthy children (Circulation 2005;112:103–9).
