TY - JOUR
T1 - A randomized, placebo-controlled, double-blinded clinical trial of colchicine to improve vascular health in people living with HIV
AU - Hays, Allison G.
AU - Schär, Michael
AU - Barditch-Crovo, Patricia
AU - Bagchi, Shashwatee
AU - Bonanno, Gabriele
AU - Meyer, Joseph
AU - Afework, Yohannes
AU - Streeb, Valerie
AU - Stradley, Samuel
AU - Kelly, Shannon
AU - Anders, Nicole M.
AU - Margolick, Joseph B.
AU - Lai, Shenghan
AU - Gerstenblith, Gary
AU - Weiss, Robert G.
N1 - Funding Information:
Funding: National Institutes of Health (HL125059, HL147660), the American Heart Association (AHA 17GRNT33670943), and the Clarence Doodeman Endowment in Cardiology at Johns Hopkins University School of Medicine. Colchicine levels were determined by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (NIH grants P30CA006973 and UL1TR003098, and the Shared Instrument Grant S10OD020091). A.G.H. is supported by the Magic that Matters Fund of Johns Hopkins Medicine, NIH/NHLBI 1R01HL147660, and the Johns Hopkins Center for AIDS Research (P30AI094189).
Funding Information:
Funding: National Institutes of Health (HL125059, HL147660), the American Heart Association (AHA 17GRNT33670943), and the Clarence Doodeman Endowment in Cardiology at Johns Hopkins University School of Medicine. Colchicine levels were determined by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (NIH grants P30CA006973 and UL1TR003098, and the Shared Instrument Grant S10OD020091). A.G.H. is supported by the Magic that Matters Fund of Johns Hopkins Medicine, NIH/NHLBI 1R01HL147660, and the Johns Hopkins Center for AIDS Research (P30AI094189)
Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Objectives:People living with HIV (PWH) experience an increased burden of coronary artery disease (CAD) believed to be related, in part, to an interplay of chronically increased inflammation and traditional risk factors. Recent trials suggest cardiovascular benefits of the anti-inflammatory, colchicine, in HIV-seronegative CAD patients. However, the impact of colchicine on impaired vascular health, as measured by coronary endothelial function (CEF), an independent contributor to CAD, has not been studied in PWH. We tested the hypothesis that colchicine improves vascular health in PWH.Design:This was a randomized, placebo-controlled, double-blinded trial in 81 PWH to test whether low-dose colchicine (0.6 mg daily) improves CEF over 8-24 weeks.Methods:Coronary and systemic endothelial function and serum inflammatory markers were measured at baseline, and at 8 and 24 weeks. The primary endpoint was CEF, measured as the change in coronary blood flow from rest to that during an isometric handgrip exercise, an endothelial-dependent stressor, measured with non-invasive MRI at 8 weeks.Results:Colchicine was well tolerated and not associated with increased adverse events. However, there were no significant improvements in coronary or systemic endothelial function or reductions in serum inflammatory markers at 8 or 24 weeks with colchicine as compared to placebo.Conclusions:In PWH with no history of CAD, low-dose colchicine was well tolerated but did not improve impaired coronary endothelial function, a predictor of cardiovascular events. These findings suggest that this anti-inflammatory approach using colchicine in PWH does not improve vascular health, the central, early driver of coronary atherosclerosis.
AB - Objectives:People living with HIV (PWH) experience an increased burden of coronary artery disease (CAD) believed to be related, in part, to an interplay of chronically increased inflammation and traditional risk factors. Recent trials suggest cardiovascular benefits of the anti-inflammatory, colchicine, in HIV-seronegative CAD patients. However, the impact of colchicine on impaired vascular health, as measured by coronary endothelial function (CEF), an independent contributor to CAD, has not been studied in PWH. We tested the hypothesis that colchicine improves vascular health in PWH.Design:This was a randomized, placebo-controlled, double-blinded trial in 81 PWH to test whether low-dose colchicine (0.6 mg daily) improves CEF over 8-24 weeks.Methods:Coronary and systemic endothelial function and serum inflammatory markers were measured at baseline, and at 8 and 24 weeks. The primary endpoint was CEF, measured as the change in coronary blood flow from rest to that during an isometric handgrip exercise, an endothelial-dependent stressor, measured with non-invasive MRI at 8 weeks.Results:Colchicine was well tolerated and not associated with increased adverse events. However, there were no significant improvements in coronary or systemic endothelial function or reductions in serum inflammatory markers at 8 or 24 weeks with colchicine as compared to placebo.Conclusions:In PWH with no history of CAD, low-dose colchicine was well tolerated but did not improve impaired coronary endothelial function, a predictor of cardiovascular events. These findings suggest that this anti-inflammatory approach using colchicine in PWH does not improve vascular health, the central, early driver of coronary atherosclerosis.
KW - clinical trial
KW - coronary artery disease
KW - coronary endothelial function
KW - HIV
KW - inflammation
UR - http://www.scopus.com/inward/record.url?scp=85106069541&partnerID=8YFLogxK
U2 - 10.1097/QAD.0000000000002845
DO - 10.1097/QAD.0000000000002845
M3 - Article
C2 - 33587443
AN - SCOPUS:85106069541
SN - 0269-9370
VL - 35
SP - 1041
EP - 1050
JO - AIDS
JF - AIDS
IS - 7
ER -