TY - JOUR
T1 - Current use of statins reduces risk of HIV rebound on suppressive HAART
AU - Drechsler, Henning
AU - Ayers, Colby
AU - Cutrell, James
AU - Maalouf, Naim
AU - Tebas, Pablo
AU - Bedimo, Roger
N1 - Funding Information:
HD, CA, JC, and NM declare that they have no conflicts of interest. PT is a consultant for Merck Pharmaceuticals and member of the Glaxo Adjudication Committee. RB has received research funding from Merck & Co and from Bristol-Myers Squibb and serves in the Scientific Advisory Board of Merck & Co, Bristol-Myers Squibb, and Theratechnologies. This does not alter our adherence to PLOS ONE policies on sharing data and materials as detailed in the PLOS ONE online guide for authors ( http://www.PLOSone.org/static/editorial.action#competing ).
Publisher Copyright:
© 2017, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Background: Despite compelling evidence for activity against HIV-1 in vitro, a virologic effect of statins has not been shown in clinical studies. Given their short plasma half-lives, such an effect may be transient and only apparent during ongoing exposure. Methods: We studied all HIV infected US-Veterans who started HAART 1995-2011, had a documented HIV viral load (VL) >1000 copies/mL, reached an undetectable VL on HAART, and had ≥1 follow-up VL within 13 months. We defined virologic failure (VF) as the first VL <1,000 copies/mL or the first of 2 consecutive VL >200 copies/mL. We built a time-updated drug exposure model for antiretrovirals (ARVs), statins, and other cardiovascular drugs (CVMs), investigating current use (yes/no), recent use (proportion of days used), and categorical use (ever/never). We used both multiply adjusted and inverse-probability-weighted (IPW) Cox models to explore the association between statin and CVM use and VF. Results: 19,324 veterans met inclusion criteria. Median follow-up was 13 months (IQR: 5-32 months); 63% experienced VF after a median time of 9 months (IQR 4-21 months). Almost 1/3 patients ever used statins but exposure comprised only 41% of follow-up time covered after initial prescription. Unadjusted, current statin use was associated with a hazard ratio (HR) for VF of 0.60 (CI: 0.56-0.65). This remained statistically significant after multivariate adjustment (MVA) for demographics, HIV and HAART parameters [HR 0.81 (CI: 0.75-0.88), p<0.001] and IPW (truncation <1%/>99%) HR: 0.83 (CI: 0.75-0.92), p<0.001]. No independent association was observed for other CVMs. The association between categorical-statin use and VF after MVA was much weaker: HR 0.94 (CI: 0.88-1.00, p = 0.04). Conclusion: Current statin exposure was associated with reduced risk of VF in univariate, multivariate, and inverse-probability-weighted models. Our results highlight the importance of time-updated medication exposure models for observational studies.
AB - Background: Despite compelling evidence for activity against HIV-1 in vitro, a virologic effect of statins has not been shown in clinical studies. Given their short plasma half-lives, such an effect may be transient and only apparent during ongoing exposure. Methods: We studied all HIV infected US-Veterans who started HAART 1995-2011, had a documented HIV viral load (VL) >1000 copies/mL, reached an undetectable VL on HAART, and had ≥1 follow-up VL within 13 months. We defined virologic failure (VF) as the first VL <1,000 copies/mL or the first of 2 consecutive VL >200 copies/mL. We built a time-updated drug exposure model for antiretrovirals (ARVs), statins, and other cardiovascular drugs (CVMs), investigating current use (yes/no), recent use (proportion of days used), and categorical use (ever/never). We used both multiply adjusted and inverse-probability-weighted (IPW) Cox models to explore the association between statin and CVM use and VF. Results: 19,324 veterans met inclusion criteria. Median follow-up was 13 months (IQR: 5-32 months); 63% experienced VF after a median time of 9 months (IQR 4-21 months). Almost 1/3 patients ever used statins but exposure comprised only 41% of follow-up time covered after initial prescription. Unadjusted, current statin use was associated with a hazard ratio (HR) for VF of 0.60 (CI: 0.56-0.65). This remained statistically significant after multivariate adjustment (MVA) for demographics, HIV and HAART parameters [HR 0.81 (CI: 0.75-0.88), p<0.001] and IPW (truncation <1%/>99%) HR: 0.83 (CI: 0.75-0.92), p<0.001]. No independent association was observed for other CVMs. The association between categorical-statin use and VF after MVA was much weaker: HR 0.94 (CI: 0.88-1.00, p = 0.04). Conclusion: Current statin exposure was associated with reduced risk of VF in univariate, multivariate, and inverse-probability-weighted models. Our results highlight the importance of time-updated medication exposure models for observational studies.
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U2 - 10.1371/journal.pone.0172175
DO - 10.1371/journal.pone.0172175
M3 - Article
C2 - 28249009
AN - SCOPUS:85014418041
SN - 1932-6203
VL - 12
JO - PloS one
JF - PloS one
IS - 3
M1 - e0172175
ER -