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

Samir Gupta, Changyu Shen, Sharon Moe, Lisa M. Kamendulis, Mitchell Goldman, Michael P. Dubé

Research output: Contribution to journalArticle

37 Citations (Scopus)

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. 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; -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. 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.

Original languageEnglish
Article numbere45716
JournalPLoS One
Volume7
Issue number9
DOIs
StatePublished - Sep 20 2012

Fingerprint

efavirenz
compound A 12
Tenofovir
proteinase inhibitors
Protease Inhibitors
prospective studies
Dilatation
Prospective Studies
HIV
F2-Isoprostanes
Drug therapy
Biomarkers
Brachial Artery
Vitamin D
1-methylcyclopropene
CD4 Lymphocyte Count
vitamin D
arteries
cardiovascular diseases
drug therapy

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Worsening Endothelial Function with Efavirenz Compared to Protease Inhibitors : A 12-Month Prospective Study. / Gupta, Samir; Shen, Changyu; Moe, Sharon; Kamendulis, Lisa M.; Goldman, Mitchell; Dubé, Michael P.

In: PLoS One, Vol. 7, No. 9, e45716, 20.09.2012.

Research output: Contribution to journalArticle

Gupta, Samir ; Shen, Changyu ; Moe, Sharon ; Kamendulis, Lisa M. ; Goldman, Mitchell ; Dubé, Michael P. / Worsening Endothelial Function with Efavirenz Compared to Protease Inhibitors : A 12-Month Prospective Study. In: PLoS One. 2012 ; Vol. 7, No. 9.
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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. 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; -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. 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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