Statin Therapy and Mortality in HIV-Infected Individuals; A Danish Nationwide Population-Based Cohort Study

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 i...

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Vydané v:	PloS one Ročník 8; číslo 3; s. e52828
Hlavní autori:	Rasmussen, Line D., Kronborg, Gitte, Larsen, Carsten S., Pedersen, Court, Gerstoft, Jan, Obel, Niels
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 04.03.2013 Public Library of Science (PLoS)
Predmet:	Acquired immune deficiency syndrome Adult AIDS Anti-HIV Agents - pharmacology Anti-HIV Agents - therapeutic use Anti-inflammatory agents Antiretroviral drugs Antiretroviral Therapy, Highly Active Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - drug therapy Cardiovascular Diseases - mortality Cohort analysis Comorbidity Denmark Denmark - epidemiology Diabetes mellitus Diabetes Mellitus - drug therapy Diabetes Mellitus - mortality Diagnosis Failure analysis Female Forecasts and trends Health risk assessment Highly active antiretroviral therapy HIV HIV Infections - drug therapy HIV Infections - mortality HIV patients Human immunodeficiency virus Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Identification methods Inflammation Male Medical diagnosis Medicine Middle Aged Mortality Patient outcomes Physiological aspects Poisson density functions Population studies Population-based studies Predictive control Regression analysis Renal Insufficiency, Chronic - drug therapy Renal Insufficiency, Chronic - mortality Statins Statistical analysis Studies Survival Analysis Therapy Viral Load Denmark
ISSN:	1932-6203, 1932-6203
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Shrnutí:	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. 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. 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)}. 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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: NO has received research funding from Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, GlaxoSmithKline, Abbott, Boehringer Ingelheim, Janssen-Cilag and Swedish Orphan Drugs. CP has received research funding from Abbott, Gilead and Merck Sharp & Dohme. JG has received research funding from Abbott, Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, Pharmasia, GlaxoSmithKline, Swedish Orphan Drugs and Boehringer Ingelheim. CSL has received research funding from Baxter and Crucell/SBL vaccines. GK and LDR report no conflicts of interest. The potential conflicts of interest described above do not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. Conducted the literature review: LDR. Statistical expertise: LDR NO. Revised the article critically for important intellectual content: LDR GK CSL CP JG NO. Performed the final approval of the article: LDR GK CSL CP JG NO. Obtained the funding: CP GK CSL JG NO. Performed the administrative, technical, or logistic support: LDR NO. Conceived and designed the experiments: LDR JG NO. Analyzed the data: LDR GK CSL CP JG NO. Contributed reagents/materials/analysis tools: CP GK CSL JG NO. Wrote the paper: LDR.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0052828