Worsening Endothelial Function with Efavirenz Compared to Protease Inhibitors: A 12-Month Prospective Study

Gupta, Samir K.; Shen, Changyu; Moe, Sharon M.; Kamendulis, Lisa M.; Goldman, Mitchell; Graham, Susan Marie; Dubé, Michael P.
September 2012
PLoS ONE;Sep2012, Vol. 7 Issue 9, Special section p1
Academic Journal
Objective: Changes 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. Design: We 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. Results: There 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; 23.50% (24.90%, 0.68%)] vs. protease inhibitors at 12 months [N= 11; 1.50% (20.86%, 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. Conclusion: Efavirenz 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.


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