title: Current use of statins reduces risk of HIV rebound on suppressive HAART.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Infectious Diseases Section, Medical Service, VA North Texas Health Care System, Dallas, Texas, United States of America.|Division of Infectious Diseases, Department of Medicine, University of Texas Southwestern School of Medicine, Dallas, Texas, United States of America.
authors.forename: Henning
authors.identifier: http://orcid.org/0000-0003-4026-9154
authors.initials: H
authors.lastname: Drechsler
authors.affiliation: Division of Biostatistics, Department of Clinical Sciences, University of Texas Southwestern School of Medicine, Dallas, Texas, United States of America.
authors.forename: Colby
authors.initials: C
authors.lastname: Ayers
authors.affiliation: Infectious Diseases Section, Medical Service, VA North Texas Health Care System, Dallas, Texas, United States of America.|Division of Infectious Diseases, Department of Medicine, University of Texas Southwestern School of Medicine, Dallas, Texas, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Cutrell
authors.affiliation: Infectious Diseases Section, Medical Service, VA North Texas Health Care System, Dallas, Texas, United States of America.|Division of Infectious Diseases, Department of Medicine, University of Texas Southwestern School of Medicine, Dallas, Texas, United States of America.
authors.forename: Naim
authors.initials: N
authors.lastname: Maalouf
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.affiliation: Infectious Diseases Section, Medical Service, VA North Texas Health Care System, Dallas, Texas, United States of America.|Division of Infectious Diseases, Department of Medicine, University of Texas Southwestern School of Medicine, Dallas, Texas, United States of America.
authors.forename: Roger
authors.initials: R
authors.lastname: Bedimo
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D015497:HIV-1; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014728:Veterans
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors