To help determine whether the benefits of the therapies outweigh the negative side effects, researchers at Washington University School of Medicine in St. Louis compared the occurrence of metabolic syndrome in HIV-infected patients to non-infected people.
The researchers report in the journal Clinical Infectious Diseases that the incidence of metabolic syndrome among their HIV-infected population is about 26 percent, essentially the same that in age-matched people not infected with the virus. The type or duration of HIV therapy did not affect the rate of metabolic syndrome.
Metabolic syndrome involves a constellation of symptoms, often related to obesity, that increase the risk for diabetes and heart disease. A diagnosis of metabolic syndrome is made when a patient has at least three of the following symptoms: abdominal obesity, high triglyceride levels, low HDL (good) cholesterol, elevated blood glucose and hypertension.
Since the mid 1990s, most HIV-infected patients have been treated with highly active antiretroviral therapy (HAART). During those years, there have been major reductions in morbidity and mortality from AIDS, but HAART and its major class of drugs, protease inhibitors, seem to be related to metabolic changes that increase the risk of cardiovascular disease.
"When HAART first became widespread in the mid- to late 1990's, clinicians began to notice really unusual things such as more deposition of fat around the mid-belly along with fat loss in the extremities, as well as extreme elevations in cholesterol or triglycerides," says first author Kristin E. Mondy, M.D., assistant professor of medicine in the Division of Infectious Diseases. "They were the sorts of changes you might otherwise see in obese people, and most HIV-infected patients were far from obese."
But as HAART medications have improved, the metabolic changes have become less pronounced. In addition, because physicians are aware of potential side effects such as elevated cholesterol and triglycerides, they watch for those problems and put many HIV-infected patients on cholesterol-lowering drugs along with HAART therapy.
Mondy says as HAART drugs have improved and physicians have found ways to stay on top of the side effects, HIV has become more of a chronic disease, like diabetes, than the death sentence it once was. And this study suggests that as HIV-infected patients live longer, they've begun to develop problems that probably are related neither to their disease nor to the therapy.
The researchers studied 471 patients from the Washington University HIV Clinic and compared them to HIV-negative people from the National Health and Nutrition Examination Survey (NHANES). Those included from the NHANES group were closely matched to HIV-infected subjects by age, sex, race and smoking status. The rate of metabolic syndrome in the HIV-infected group was 25.5 percent and in the NHANES group was 26.5 percent.
"Overall, the HIV-infected people tended to weigh less and to have lower HDL levels, higher triglycerides and lower glucose levels," says the study's senior investigator, Kevin E. Yarasheski, Ph.D., associate professor of medicine. "But it didn't seem that HIV therapy was influencing their risk for metabolic syndrome as much as the more traditional risk factors that everyone faces."
When Yarasheski, Mondy and their colleagues crunched the numbers, they found that HIV-infected patients with metabolic syndrome were more likely to be diabetic, to be older, white and have a high body-mass index. The type or duration of HIV therapy was not an independent risk factor.
Ironically, another important risk factor for metabolic syndrome was a high CD4 cell count.
That's a crucial number in HIV treatment. The CD4 count rises and falls as the patient's immune system gets stronger and weaker. Higher CD4 counts mean a healthier patient.
"As CD4 counts went up, weight also seemed to climb," Mondy says. "There's that old saying about being fat and happy. When these people are healthy and doing well, many tend to gain some weight, and that can put them at risk."
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Kristin Mondy |
Mondy says it's important to replicate these findings, but she says a strength of this study is that researchers were able to look at significant numbers of African-American men and women. Among HIV-infected African-American women, the rate of obesity was almost 45 percent. She says with rates that high, it's probably time to start investigating the efficacy of exercise and other weight-loss methods in HIV-infected people.
"The mortality risk from HIV still outweighs all other risks," says Mondy. "But as therapies have improved and people are living longer, clinicians have to be concerned about these other health problems."
And when it comes to metabolic syndrome, HIV-infected people aren't the only group at risk.
"It is a global problem in our society," Yarasheski says. "The metabolic syndrome is clearly too common in HIV-infected people, but it's too common in everyone. This is a public-health problem, and it's not limited to any particular group of people."
Mondy K, Overton ET, Grubb J, Tong S, Seyfried W, Powderly W, Yarasheski K. Metabolic syndrome in HIV-infected patients from an urban, Midwestern U.S. outpatient population. Clinical Infectious Diseases , vol. 44: pp. 726-734. March 1, 2007 DOI: 10.1086/511679
This research was supported by grants from the National Institutes of Health.
Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
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Metabolic syndrome as common in HIV-infected people as in general population