title: Endothelial, inflammatory, coagulation, metabolic effects and safety of etravirine in HIV-uninfected volunteers.
abstract: The innate proatherosclerotic properties of non-nucleoside reverse transcriptase inhibitors have not previously been examined. Therefore, we performed a pilot study of etravirine (ETR) in healthy volunteers over 28 days. This investigation also allowed us to evaluate the safety of ETR over a period commonly used for HIV postexposure prophylaxis. ETR 200 mg twice daily was given to 28 healthy HIV-uninfected volunteers over 28 days. Flow-mediated dilation (FMD) of the brachial artery and circulating markers of inflammation, coagulation, and metabolism were measured at entry and at day 28. These circulating markers were also measured at day 35. Of the initial 28 subjects, 23 completed both entry and day 28 procedures. Two subjects were discontinued due to development of rash. No other major toxicities developed. The change in FMD over 28 days was minimal and not significant (0.03 [-3.21, 0.97] %; p=0.36). The post hoc estimated detectable absolute change in FMD with the 23 subjects in our study was 2.26%, which is an effect size that has been associated with future cardiovascular event rates in the general population; thus our study had sufficient power to find clinically relevant changes in FMD. In addition, there were no significant changes in any of the circulating markers from entry to day 28 or from day 28 to day 35. ETR did not demonstrate any innate proatherosclerotic properties over 28 days in these HIV-uninfected volunteers. ETR was generally well tolerated. Larger studies are warranted to confirm that ETR can be used safely as part of HIV postexposure prophylaxis regimens.
authors.affiliation: Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, USA. sgupta1@iupui.edu
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Deming
authors.initials: D
authors.lastname: Mi
authors.forename: Ziyue
authors.initials: Z
authors.lastname: Liu
authors.forename: Chandan
authors.initials: C
authors.lastname: Saha
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood* / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D001916:Brachial Artery; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D018023:HIV Seronegativity / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010865:Pilot Projects; D011724:Pyridazines / Q000009:adverse effects / Q000494:pharmacology*; D011743:Pyrimidines; D012039:Regional Blood Flow
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine