A randomized, controlled trial of the effect of rilpivirine versus efavirenz on cardiovascular risk in healthy volunteers

Samir Gupta, James E. Slaven, Lisa M. Kamendulis, Ziyue Liu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objectives: The HIV NNRTI rilpivirine is being evaluated as a possible agent for HIV pre-exposure prophylaxis. We have recently shown that the NNRTI efavirenz may impair endothelial function assessed as flow-mediated dilation (FMD), but whether this impairment is also found with rilpivirine is unknown. We sought to compare cardiovascular risk profiles between efavirenz and rilpivirine in healthy volunteers. Methods: We performed a prospective, randomized, open-label trial in 40 HIV-uninfected healthy volunteers who were randomized 1:1 to either efavirenz or rilpivirine. Vascular indices, metabolic parameters, inflammatory biomarkers and oxidative stress were measured before and after 4 weeks of treatment. This study is registered at ClinicalTrials.gov (NCT01585038). Results: There were no significant differences in 4 week mean (SD) changes in FMD between efavirenz and rilpivirine [0.089 (3.65)% versus 0.63 (2.42) %;P=0.77]. There were also no significant differences in 4 week changes in high-sensitivity C-reactive protein, IL-6, soluble vascular cell adhesion molecule-1, HDL-cholesterol, triglycerides or homeostasis model assessment-insulin resistance. However, efavirenz led to significant increases in total cholesterol [19.39 (23.9) versus 25.78 (16.5) mg/dL; P,0.001], LDL cholesterol [13.29 (19.5) versus 22.24 (13.4) mg/dL; P=0.009] and F2-isoprostanes [92.7 (178.6) versus 2101.4 (215.7) pg/mL; P=0.019] compared with rilpivirine. Two participants from each study group discontinued prematurely for adverse events. Conclusions: There were no significant differences in the changes in endothelial function over 1 month between the efavirenz and rilpivirine groups, although efavirenz had worse lipid changes compared with rilpivirine. Longerterm studies are required for confirmation.

Original languageEnglish (US)
Article numberdkv195
Pages (from-to)2889-2893
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume70
Issue number10
DOIs
StatePublished - Oct 1 2015

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Rilpivirine
efavirenz
Healthy Volunteers
Randomized Controlled Trials
HIV
Dilatation
F2-Isoprostanes
Vascular Cell Adhesion Molecule-1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

A randomized, controlled trial of the effect of rilpivirine versus efavirenz on cardiovascular risk in healthy volunteers. / Gupta, Samir; Slaven, James E.; Kamendulis, Lisa M.; Liu, Ziyue.

In: Journal of Antimicrobial Chemotherapy, Vol. 70, No. 10, dkv195, 01.10.2015, p. 2889-2893.

Research output: Contribution to journalArticle

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title = "A randomized, controlled trial of the effect of rilpivirine versus efavirenz on cardiovascular risk in healthy volunteers",
abstract = "Objectives: The HIV NNRTI rilpivirine is being evaluated as a possible agent for HIV pre-exposure prophylaxis. We have recently shown that the NNRTI efavirenz may impair endothelial function assessed as flow-mediated dilation (FMD), but whether this impairment is also found with rilpivirine is unknown. We sought to compare cardiovascular risk profiles between efavirenz and rilpivirine in healthy volunteers. Methods: We performed a prospective, randomized, open-label trial in 40 HIV-uninfected healthy volunteers who were randomized 1:1 to either efavirenz or rilpivirine. Vascular indices, metabolic parameters, inflammatory biomarkers and oxidative stress were measured before and after 4 weeks of treatment. This study is registered at ClinicalTrials.gov (NCT01585038). Results: There were no significant differences in 4 week mean (SD) changes in FMD between efavirenz and rilpivirine [0.089 (3.65){\%} versus 0.63 (2.42) {\%};P=0.77]. There were also no significant differences in 4 week changes in high-sensitivity C-reactive protein, IL-6, soluble vascular cell adhesion molecule-1, HDL-cholesterol, triglycerides or homeostasis model assessment-insulin resistance. However, efavirenz led to significant increases in total cholesterol [19.39 (23.9) versus 25.78 (16.5) mg/dL; P,0.001], LDL cholesterol [13.29 (19.5) versus 22.24 (13.4) mg/dL; P=0.009] and F2-isoprostanes [92.7 (178.6) versus 2101.4 (215.7) pg/mL; P=0.019] compared with rilpivirine. Two participants from each study group discontinued prematurely for adverse events. Conclusions: There were no significant differences in the changes in endothelial function over 1 month between the efavirenz and rilpivirine groups, although efavirenz had worse lipid changes compared with rilpivirine. Longerterm studies are required for confirmation.",
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N2 - Objectives: The HIV NNRTI rilpivirine is being evaluated as a possible agent for HIV pre-exposure prophylaxis. We have recently shown that the NNRTI efavirenz may impair endothelial function assessed as flow-mediated dilation (FMD), but whether this impairment is also found with rilpivirine is unknown. We sought to compare cardiovascular risk profiles between efavirenz and rilpivirine in healthy volunteers. Methods: We performed a prospective, randomized, open-label trial in 40 HIV-uninfected healthy volunteers who were randomized 1:1 to either efavirenz or rilpivirine. Vascular indices, metabolic parameters, inflammatory biomarkers and oxidative stress were measured before and after 4 weeks of treatment. This study is registered at ClinicalTrials.gov (NCT01585038). Results: There were no significant differences in 4 week mean (SD) changes in FMD between efavirenz and rilpivirine [0.089 (3.65)% versus 0.63 (2.42) %;P=0.77]. There were also no significant differences in 4 week changes in high-sensitivity C-reactive protein, IL-6, soluble vascular cell adhesion molecule-1, HDL-cholesterol, triglycerides or homeostasis model assessment-insulin resistance. However, efavirenz led to significant increases in total cholesterol [19.39 (23.9) versus 25.78 (16.5) mg/dL; P,0.001], LDL cholesterol [13.29 (19.5) versus 22.24 (13.4) mg/dL; P=0.009] and F2-isoprostanes [92.7 (178.6) versus 2101.4 (215.7) pg/mL; P=0.019] compared with rilpivirine. Two participants from each study group discontinued prematurely for adverse events. Conclusions: There were no significant differences in the changes in endothelial function over 1 month between the efavirenz and rilpivirine groups, although efavirenz had worse lipid changes compared with rilpivirine. Longerterm studies are required for confirmation.

AB - Objectives: The HIV NNRTI rilpivirine is being evaluated as a possible agent for HIV pre-exposure prophylaxis. We have recently shown that the NNRTI efavirenz may impair endothelial function assessed as flow-mediated dilation (FMD), but whether this impairment is also found with rilpivirine is unknown. We sought to compare cardiovascular risk profiles between efavirenz and rilpivirine in healthy volunteers. Methods: We performed a prospective, randomized, open-label trial in 40 HIV-uninfected healthy volunteers who were randomized 1:1 to either efavirenz or rilpivirine. Vascular indices, metabolic parameters, inflammatory biomarkers and oxidative stress were measured before and after 4 weeks of treatment. This study is registered at ClinicalTrials.gov (NCT01585038). Results: There were no significant differences in 4 week mean (SD) changes in FMD between efavirenz and rilpivirine [0.089 (3.65)% versus 0.63 (2.42) %;P=0.77]. There were also no significant differences in 4 week changes in high-sensitivity C-reactive protein, IL-6, soluble vascular cell adhesion molecule-1, HDL-cholesterol, triglycerides or homeostasis model assessment-insulin resistance. However, efavirenz led to significant increases in total cholesterol [19.39 (23.9) versus 25.78 (16.5) mg/dL; P,0.001], LDL cholesterol [13.29 (19.5) versus 22.24 (13.4) mg/dL; P=0.009] and F2-isoprostanes [92.7 (178.6) versus 2101.4 (215.7) pg/mL; P=0.019] compared with rilpivirine. Two participants from each study group discontinued prematurely for adverse events. Conclusions: There were no significant differences in the changes in endothelial function over 1 month between the efavirenz and rilpivirine groups, although efavirenz had worse lipid changes compared with rilpivirine. Longerterm studies are required for confirmation.

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