title: A randomized, controlled trial of the effect of rilpivirine versus efavirenz on cardiovascular risk in healthy volunteers.
abstract: OBJECTIVE
  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 -5.78 (16.5) mg/dL; P < 0.001], LDL-cholesterol [13.29 (19.5) versus -2.24 (13.4) mg/dL; P = 0.009] and F2-isoprostanes [92.7 (178.6) versus -101.4 (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. Longer-term studies are required for confirmation.
authors.affiliation: Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, IN, USA sgupta1@iu.edu.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: Department of Biostatistics, Indiana University School of Medicine and School of Public Health, Indianapolis, IN, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Slaven
authors.affiliation: Department of Environmental Health, Indiana University, Bloomington, IN, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Kamendulis
authors.affiliation: Department of Biostatistics, Indiana University School of Medicine and School of Public Health, Indianapolis, IN, USA.
authors.forename: Ziyue
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D048588:Benzoxazines / Q000009:adverse effects* / Q000627:therapeutic use; D001663:Bilirubin / Q000378:metabolism; D015415:Biomarkers; D066126:Cardiotoxicity; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003521:Cyclopropanes; D028441:F2-Isoprostanes / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D018384:Oxidative Stress; D000068696:Rilpivirine / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D015415:Biomarkers; D003521:Cyclopropanes; D028441:F2-Isoprostanes; D000068696:Rilpivirine; C098320:efavirenz; D001663:Bilirubin