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Baseline Vitamin D Deficiency Decreases the Effectiveness of Statins in HIV-Infected Adults on Antiretroviral Therapy

Hileman, Corrilynn O. MD, MS; Tangpricha, Vin MD; Sattar, Abdus MS, PhD; McComsey, Grace A. MD

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 15th, 2017 - Volume 74 - Issue 5 - p 539–547
doi: 10.1097/QAI.0000000000001281
Clinical Science

Objective: Vitamin D deficiency is common in HIV. Statins may increase vitamin D, and it is unknown whether vitamin D modifies the effect of statins on cardiovascular disease.

Design: SATURN-HIV was a 96-week, randomized, placebo-controlled trial designed to evaluate the effect of rosuvastatin on immune activation and subclinical vascular disease in HIV-infected adults on antiretroviral therapy. This analysis focuses on the prespecified secondary endpoint 25-hydroxyvitamin D [25(OH)D] concentrations.

Methods: Mixed effects linear modeling and analysis of variance were used to assess the rosuvastatin effect on plasma 25(OH)D concentrations over time and to determine whether baseline vitamin D modifies the rosuvastatin effect on changes in outcomes over the trial.

Results: Hundred forty-seven adults were randomized (72 to rosuvastatin and 75 to placebo); 78% were men, 68% African American, with a mean age of 45 years. Baseline 25(OH)D concentrations were similar (overall mean 18 ng/mL) with 65% of participants below 20 ng/mL. Changes in 25(OH)D at 96 weeks were small and not significant within- or between-rosuvastatin and placebo groups. There were significant group by vitamin D status interactions for changes in low-density lipoprotein–cholesterol, proportion of patrolling monocytes expressing tissue factor (CD14dimCD16+TF+), lipoprotein-associated phospholipase A2, and common carotid artery intima media thickness at most time points. For each of these outcomes, the beneficial effects of rosuvastatin were either not apparent or attenuated in participants with 25(OH)D <20 ng/mL.

Conclusions: Although 25(OH)D did not change with rosuvastatin, baseline vitamin D deficiency decreased the effectiveness of rosuvastatin. Vitamin D supplementation may be warranted for deficient patients initiating statin therapy.

*Department of Medicine, Division of Infectious Diseases, MetroHealth Medical Center, Cleveland, OH;

Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH;

Division of Endocrinology, Metabolism & Lipids, Emory University School of Medicine, Atlanta, GA;

§Endocrinology, Altanta VA Medical Center, Atlanta, GA;

Division of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH;

Department of Pediatrics, Division of Pediatric Infectious Diseases and Rheumatology, Rainbow Babies and Children's Hospital of University Hospitals Health System, Cleveland, OH; and

#Departments of Pediatrics and Medicine, Case Western Reserve University School of Medicine, Cleveland, OH.

Correspondence to: Corrilynn O. Hileman, MD, MS, Case Western Reserve School of Medicine, 2500 MetroHealth Drive, Cleveland, OH 44109 (e-mail: corrilynn.hileman@case.edu).

Supported by the National Institutes of Health (Grant numbers K23HL116209 to COH, UL1TR000454 to VT, HD070490 and NR012642 to GAM). Study drugs were provided by Astra Zeneca. Technical assistance was provided by the Center for AIDS Research, Case Western Reserve University (P30 AI36219).

C.O.H. has served on a medical advisory board for Gilead Sciences. G.A.M. has received research grants from BMS, Gilead Sciences, Merck, and GSK and has served as a consultant to BMS, Viiv/GSK, ICON, and Gilead. The remaining authors have no conflicts of interest to disclose.

Received August 04, 2016

Accepted December 19, 2016

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