title: Worsening endothelial function with efavirenz compared to protease inhibitors: a 12-month prospective study.
abstract: 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.
  
  
  METHODS
  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; -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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. sgupta1@iupui.edu
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Changyu
authors.initials: C
authors.lastname: Shen
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Kamendulis
authors.forename: Mitchell
authors.initials: M
authors.lastname: Goldman
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dubé
mesh_terms: D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; C000717427:FGF23 protein, human; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D000089703:Fibroblast Growth Factor-23; C098320:efavirenz