Important note: Information in this article was accurate in August 2000. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, August 28, 2000
Prepared by AIDS Weekly editors from staff and other reports
NewsRx -- Although researchers in the United States have been able to confirm that protease inhibitors (PI) cause hyperglycemia, hyperlipidemia, and lipodystrophy in HIV infected patients who take these antivirals, they still do not understand the mechanisms behind the complications.
"Although HIV related morbidity and mortality rates in patients with advanced HIV infection who are treated with combination antiretroviral drugs have declined, significant metabolic adverse effects associated with these regimens have been increasingly recognized," wrote S. Tsiodras and colleagues, Harvard University, Massachusetts. "However, since data from patients studied before and after initiation of protease inhibitor therapy are scant, the true effect of PIs on these metabolic changes remains unknown."
The researchers examined temporal trends in serum glucose and lipid levels after the initiation of PI therapy, and assessed whether the changes were independent of virological response and improvement in disease severity. They also sought to determine risk factors associated with the development of hyperglycemia, hyperlipidemia, and lipodystrophy in these patients ("Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy - A 5-year cohort study," Arch Intern Med 2000 Jul 10;160(13):2050-6.
They conducted a five-year historical cohort analysis in a population of 221 HIV infected patients. The patients were observed in the Infectious Diseases Clinic of a tertiary care center from October 1, 1993, to July 31, 1998.
The researchers obtained clinical and laboratory data from medical records and a computerized database. The incidences of hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and lipodystrophy were the main outcome measures. They estimated adjusted incidence rate ratios (IRRs) with Poisson regression analysis. They also performed mixed regression analyses. This allowed them to examine effects of PIs on serum lipid and glucose levels, modeled as continuous outcomes.
"The cumulative incidence of new-onset hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and lipodystrophy was 5%, 24%, 19%, and 13%, respectively," wrote Tsiodras et al. "Most of these events occurred after initiation of PI therapy. Protease inhibitors were independently associated with hyperglycemia (adjusted IRR, 5.0; 95% confidence interval [CI], 1.3-19.4), hypercholesterolemia (adjusted IRR, 2.8; 95% CI, 1.5-5.2), hypertriglyceridemia (adjusted IRR, 6.1; 95% CI, 3.1-11.7), and lipodystrophy (adjusted IRR, 5.1; 95% CI, 1.9-13.9)."
They found that lipodystrophy complications were also associated with the use of anabolic steroids and psychotropic medications. When potential intermediate variables (e.g., virological suppression and increase in body weight) were included, they did not reduce the magnitude of the association with PIs, reported Tsiodras et al.
According to the researchers, there was a stronger association between hypertriglyceridemia and ritonavir than there was with other PIs (Wald test, P=.02). However, the incidence of hyperglycemia, hypercholesterolemia, and lipodystrophy did not vary significantly across the different types of PIs used.
"Longitudinal mixed models confirmed that serum lipid levels were more substantially affected by antiretroviral therapy, particularly PIs, than serum glucose levels," concluded Tsiodras et al. "Similarly, controlling for surrogate markers did not abolish the strong association between PIs and increase in serum lipid levels. We found an independent association between PI use and hyperglycemia, hyperlipidemia, and lipodystrophy that is not explained by the antiviral and therapeutic effect of PIs."
For additional information, contact S. Tsiodras, Harvard University, School of Medicine, Beth Israel Deaconess Medical Center, Division of Infectious Diseases, West Campus, 1 Autumn St., Kennedy Bldg, 6th Floor, Boston, Massachusetts 02215, USA.
Key points reported in this study are:
This article was prepared by AIDS Weekly editors from staff and other reports.
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