FOR FURTHER INFORMATION CONTACT:Pam Barber, Columbus Children's Hospital, (614) 722-4598Amy Nance, Columbus Children's Hospital, (614) 722-4592
Embargoed for release May 7, 2002
FIRST STUDY OF ITS KIND SHOWS VALUABLE HIV PROTEASE INHIBITOR THERAPIES ENHANCE LIFE EXPECTANCIES FOR PEOPLE WITH HIV BUT CAN CAUSE ADVERSE EFFECTS
Drugs Injure Blood Vessel Cells, May Promote Coronary Artery Disease or Low Birth Weight Babies
BALTIMORE, MAY 7, 2002 --Breakthroughs in protease inhibitors (PIs), drug therapies designed to combat HIV, have enhanced the life expectancies of those infected with the virus. However, there is increasing evidence that PI therapies have significant adverse effects, including the promotion of coronary artery disease, possibly causing premature births in pregnant women.
In the first study of its kind, researchers at the Columbus Children's Research Institute Center of Developmental Pharmacology and Toxicology, located on the campus of Columbus Children's Hospital, tested the effects from PIs on the function and survival of vascular endothelial cells (cells that line blood vessels). The study showed there were direct toxicities from PIs to the endothelium. These direct toxicities may contribute to PI-related atherosclerosis (hardening of the arteries), which is typically seen only in older males, as well as an increased risk of PI-related low birth weight (LBW) babies born to HIV-positive women.
Investigator John Anthony Bauer, Ph.D., associate professor of Pediatrics, presented the findings Tuesday, May 7 at the 2002 Pediatric Academic Societies' (PAS) annual meeting in Baltimore.
"In the early '90s, the Food and Drug Administration (FDA) was under public and political pressure to fast-track PIs to make them available to the growing HIV-positive population," Dr. Bauer said. "In part, because of this, some of the adverse drug effects were not identified in the pre-marketing phase. As a result of the innovations with the PI drug class, HIV-positive patients are living longer, but only now are healthcare providers becoming aware of the complications."
The study examined adverse effects associated with PI drugs on blood vessel endothelial cells from humans. Because the endothelial cells act as a protective coating to keep vessels healthy, they are critical in maintaining the placenta where the cells form capillaries. The placenta's two-tube network system allows for nutrient and gas exchanges between the mother and fetus without the blood systems coming in contact with one another. Dosing of PI drugs throughout the pregnancy and at the time of delivery helps prevent vertical transmission of HIV between the mother and baby. However, other recent studies suggest that HIV PIs may promote at-birth problems, particularly LBW babies.
"Clinicians aggressively treat pregnant women with HIV drug therapies, including PIs, because it reduces the risk of passing HIV to the fetus, and also because we have no other option for treatment at this time," Dr. Bauer said. "We need to consider this population when developing new drugs to help reduce the risks associated with the current therapies, such as LBW babies and premature labor."
Given the importance of endothelial cell health for prevention of athlerosclerosis and maintaining a functional placenta, the studies tested if endothelial cells are vulnerable to PI toxicity. "When human endothelial cells were exposed to common concentrations of PIs, they were found to be more stressed than expected," Dr. Bauer said. "It has been recently shown that PI drugs can alter blood lipid levels, which might also promote atherosclerosis, but in our studies we showed for the first time that the endothelial cells that are so important in preventing vessel disease are also directly injured with these agents. As a result of our findings, our current goals are to determine exactly how this cell toxicity occurs and what specific components of the cell are being affected. This is the best way for us to rationally design newer and better therapies. Moving forward, we are hopeful that PI therapies can be redesigned without high levels of toxicity or strategies can be developed to protect the endothelial cells from PIs, thus making these drugs more valuable."
Columbus Children's Hospital ranks among the top 10 in National Institutes of Health research awards and grants to freestanding children's hospitals in the country. With nearly 500,000 patient visits each year, Children's Hospital is a 110-year-old pediatric healthcare network treating newborns through age 21. In 2001, the Children's Research Institute conducted more than 105 research projects. Pediatric Clinical Trials International (PCTI), a site management organization affiliated with the hospital, also coordinated more than 50 clinical trials. In addition to having one of the largest ambulatory programs in the country, Children's offers specialty programs and services. Each year, more than 75,000 consumers receive health and wellness education and 2,000 students from 100 institutions and 500 residents receive training at Children's. More information on Children's Hospital of Columbus is available by calling (614) 722-KIDS (5437) or through the hospital's Web site at http://www.columbuschildrens.com.
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