Abstract
ObjectiveChanges in endothelial function, measured as flow-mediated dilation (FMD) of the brachial artery, has not been systematically assessed beyond 6 months of initiation of antiretroviral therapy (ART) when drug-related effects might offset initial improvements with virologic control.DesignWe assessed 6 and 12 month changes in FMD [presented as median (quartile 1, quartile 3)] and circulating HIV and cardiovascular biomarkers in 23 subjects initiating ART.ResultsThere were no significant changes in FMD at 6 or 12 months overall despite significant increases in CD4 cell count and HDL-C and reductions in HIV RNA level, MCP-1, IP-10, sVCAM-1, sTNFR2, and sCD14. However, there were significant differences (P = 0.04) in the changes in FMD between those receiving efavirenz [N = 12; −3.50% (−4.90%, 0.68%)] vs. protease inhibitors at 12 months [N = 11; 1.50% (−0.86%, 4.56%)]. The differences in changes in FMD between those receiving and not receiving emtricitabine/tenofovir/efavirenz were more pronounced and were significantly different at both 6 and 12 months (P<0.02 for both). Additional studies showed no significant differences in changes in 25-(OH)-vitamin D, PTH, FGF-23, of F2-isoprostane levels between efavirenz and PI use or between those receiving and not receiving emtricitabine/tenofovir/efavirenz.ConclusionEfavirenz use was associated with reduced FMD at 12 months compared to PI-based regimens while emtricitabine/tenofovir/efavirenz was associated with reduced FMD at both 6 and 12 months compared to those not receiving this combination. Long-term effects of antiretrovirals on endothelial function may play an important role in the risk of cardiovascular disease in HIV-infected patients.
Highlights
It has been suggested that both HIV infection itself and the antiretroviral therapies (ART) used to treat HIV contribute to the increased risk of cardiovascular disease (CVD) seen in this population [1]
It seems plausible to hypothesize that any initial improvements in flow-mediated dilation (FMD) with viral load reduction may subsequently be negated by ART-related toxic effects
We examined these possibilities in a prospective, 12-month study assessing changes in FMD in 23 subjects initiating ART
Summary
It has been suggested that both HIV infection itself and the antiretroviral therapies (ART) used to treat HIV contribute to the increased risk of cardiovascular disease (CVD) seen in this population [1]. In ACTG 5152s, endothelial function, as measured by flow-mediated dilation (FMD) of the brachial artery, improved with antiretroviral therapy, regardless of its component drugs or associated lipid abnormalities, over the first six months of treatment [3]. Is seems likely that specific ART regimens may lead to greater CVD risk than others. We examined these possibilities in a prospective, 12-month study assessing changes in FMD in 23 subjects initiating ART
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