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Current use of statins reduces risk of HIV rebound on suppressive HAART.

Current use of statins reduces risk of HIV rebound on suppressive HAART.
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Drechsler H, Ayers C, Cutrell J, Maalouf N, Tebas P, Bedimo R,


Drechsler H, Ayers C, Cutrell J, Maalouf N, Tebas P, Bedimo R, (click to view)

Drechsler H, Ayers C, Cutrell J, Maalouf N, Tebas P, Bedimo R,

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PloS one 2017 03 0112(3) e0172175 doi 10.1371/journal.pone.0172175

Abstract
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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