The study also found a 75 percent drop in the overall death rate among VA's HIV patients between 1993 and 2001, consistent with other evidence that HAART--which became available in 1996 and was quickly adopted by VA practitioners--may prolong survival. "Fears about vascular disease as a side effect of these drugs shouldn't keep patients and their doctors from using the best treatments available, consistent with guidelines," said study leader Samuel A. Bozzette, MD, PhD, an infectious disease specialist with the VA San Diego Health Care System.
Though the study is the largest of its kind to date, it analyzed data only from an eight-year span--1993 to 2001--and may not reflect the rate of serious vascular disease with longer-term use of HAART.
"It's reasonable to expect that metabolic abnormalities will be harmful to people with HIV over a longer time frame," said Bozzette, who is also affiliated with the University of California at San Diego and the RAND Corporation. He said HIV patients must be monitored carefully for vascular disease and other side effects, and treated accordingly.
The increased use of potent combinations of anti-HIV drugs has led to a sharp decline in the number of AIDS-related death since 1996. Today, patients infected with HIV are leading longer, healthier lives. However, the drugs helping to keep them alive--usually a combination of reverse transcriptase inhibitors and protease inhibitors--can also cause serious side effects, affecting the heart, blood, kidneys, liver and nervous system.
Protease inhibitors, in particular, have been associated with metabolic abnormalities such as blood-sugar imbalances and diabetes, redistribution of body fat, or "protease paunch," and defects in how the body metabolizes fat. Over time this could damage the vessels that supply blood to the heart or brain, resulting in angina, heart attack, stroke or other life-threatening conditions.
On the other hand, there is some evidence that HIV itself can cause vascular disease, and HAART may protect against this damage by suppressing the virus. Research is ongoing to better understand how HIV, HAART and vascular disease are interrelated. Of the 36,766 patients included in the study, only 21,659 were still alive at the end of the eight-year study period, reflecting the deadly toll of HIV and AIDS. However, the rate of death from any cause dropped sharply from 1993--when 2,273 of 16,763 patients died--to 2001, when 410 of 17,891 patients died.
According to the Centers for Disease Control and Prevention, 800,000 to 900,000 Americans are living with HIV infection. VA, the nation's largest health-care system, is also the nation's largest single provider of health care to those with HIV. In fiscal year 2001, more than 18,500 veterans received care for HIV at VA medical centers and clinics. VA's national databases-- a unique, integrated system for electronically tracking patient information and an array of quality indicators--enabled the study authors to extract anonymous information on HIV patients and analyze their health histories.
Bozzette and colleagues conducted their research through VA's Quality Enhancement Research Initiative for HIV, Center for Research in Patient Oriented Care, and Center for Quality Management in Public Health. Collaborating on the study were Christopher F. Ake, PhD, of VA; Henry K. Tam, PhD, of VA and UCSD; Sophia W. Chang, MD, MPH, of VA; and Thomas A. Louis, PhD, of The Johns Hopkins Bloomberg School of Public Health.
The study was funded by VA, which spends up to $8 million annually on HIV-related research, and several pharmaceutical companies participating in the Oversight Committee for the Evaluation of the Metabolic Complications of Highly Active Antiretroviral Therapy, a group convened by the European Agency for the Evaluation of Medicinal Products.
Journal
New England Journal of Medicine