Statin therapy and mortality in HIV-infected individuals; a Danish nationwide population-based cohort study

PLoS One. 2013;8(3):e52828. doi: 10.1371/journal.pone.0052828. Epub 2013 Mar 4.

Abstract

Background: Recent studies have suggested that statins possess diverse immune modulatory and anti-inflammatory properties. As statins might attenuate inflammation, statin therapy has been hypothesized to reduce mortality in HIV-infected individuals. We therefore used a Danish nationwide cohort of HIV-infected individuals to estimate the impact of statin use on mortality before and after a diagnosis of cardiovascular disease, chronic kidney disease or diabetes.

Methods: We identified all Danish HIV-infected individuals (1,738) who initiated HAART after 1 January 1998, and achieved virological suppression within 180 days. Date of first redemption of a prescription of statin was obtained from the Danish National Prescription Registry. We used Poisson regression analysis to assess adjusted mortality rate ratios (aMRR). First, time was censored at date of virological failure (VL >500 copies/ml). Second, time was not censored at virological failure. All analyses were adjusted for potential confounders.

Results: In the analyses confined to observation time without virological failure (+ censoring) statin therapy was associated with a non-statistically significant reduced rate of death (aMRR 0.75; 95% CI: 0.33-1.68). No difference was observed in the analysis with no censoring (aMRR 1.17; 95% CI: 0.66-2.07). Use of statin seemed to reduce mortality in individuals after a diagnosis of comorbidity {(+ censoring: aMRR: 0.34; 95% CI: 0.11-1.04), (-censoring: aMRR: 0.64; 95% CI: 0.32-1.29)}. No difference in rate of death could be detected before first date of diagnosis of comorbidity {(+ censoring: aMRR: 1.12; 95% CI: 0.34-3.62), (-censoring: aMRR: 0.90; 95% CI: 0.28-2.88)}.

Conclusion: Statin therapy might reduce all-cause mortality in HIV-infected individuals, but the impact on individuals with no comorbidity seems small or absent. An unambiguous proof of a causal relation can only be obtained in a randomized controlled trial, but the sample size predicted may be prohibitive for its conduct.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / mortality
  • Comorbidity
  • Denmark / epidemiology
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / mortality
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / mortality
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / mortality
  • Survival Analysis
  • Viral Load

Substances

  • Anti-HIV Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors

Grants and funding

The authors thank the NOVO Nordic Foundation, University of Southern Denmark and the Clinical Institute of Copenhagen University for financial support of the Danish HIV cohort study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.