The use of combinations of antiretroviral drugs including nucleoside analogs, protease inhibitors (PIs) and reverse transcriptase inhibitors - collectively termed highly active anti-retroviral therapy (HAART) - has resulted in a dramatic improvement in health status for a large number of HIV-infected individuals.
Side effects in many users, however, cause non-adherence to treatment regimes and concern over their long-term use in the management of chronic HIV infection. The adverse effects of PIs include abnormalities in lipid metabolism, insulin resistance, and premature atherosclerosis. Whether the latter is caused directly by the drugs or as a consequence of lipid abnormalities and insulin resistance has not been clear- until now.
A report in the February 3 issue of the Journal of Clinical Investigation shows that HIV protease inhibitors directly promote atherosclerosis in mice. Led by Eric Smart, the researchers from the University of Kentucky Medical School in Lexington also examined the situation in human cells, and found that protease inhibitors induced changes in particular cells (called macrophages) that are like those seen in atherosclerotic lesions.
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