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EFFECTS OF VITAMIN D SUPPLEMENTATION ON CAROTID INTIMA-MEDIA THICKNESS IN HIV+ YOUTH
Allison R. Eckard1, Paolo Raggi2, Mary Ann O'Riordan3, Julia C. Rosebush4, Danielle Labbato3, Ann Chahroudi4, Joshua H. Ruff4, Chris T. Longenecker3, Vin Tangpricha4, Grace A. McComsey3
1Med Univ of South Carolina, Charleston, SC, USA,2Mazankowski Alberta Heart Inst, Edmonton, Canada,3Case Western Reserve Univ, Cleveland, OH, USA,4Emory Univ, Atlanta, GA, USA
HIV+ youth are at an increased risk of cardiovascular disease (CVD). Vitamin D deficiency is associated with CVD risk in HIV, but it is not known whether supplementation could affect this risk.
This is a 24-month randomized, active-control, double-blind trial comparing 2 different monthly vitamin D3 doses [60,000 (medium) or 120,000 (high) IU/month] vs. control of 18,000 IU/month in 8-26 year old HIV+ youth on ART with baseline 25-hydroxyvitamin D (25(OH)D) ≤30 ng/mL & HIV-1 RNA <1000 copies/mL. Carotid IMT was measured at baseline & 24 months. Comparisons of changes in IMT were made between the HIV+ control arm vs. combined supplementation arms (medium+high) & within these groups using appropriate two-sample tests. A matched healthy uninfected group was enrolled in a similarly-designed parallel study for comparison.
We enrolled 102 HIV+ subjects: 64% men, 89% black, median age of 20 years. HIV & ART duration were 8 & 3 years, respectively with a CD4 count of 652 cells/mm³. Baseline 25(OH)D was similar between groups (controls: 17 (11, 21) vs. supplementation group: 18 (14, 22) ng/mL; P=0.49) and increased to 32 (25, 38) and 41 (31, 46) ng/mL in the control and supplementation (medium+high) dose groups at 24 months, respectively (within & between groups P<0.001). Baseline bulb (0.65 vs. 0.63 mm, P=0.13) and common carotid artery (CCA) IMT (0.69 vs. 0.56 mm, P=0.81) were similar between groups. Over 24 months, bulb & CCA IMT decreased only in the control arm (Figure 1), with changes in bulb IMT being significantly different than supplementation arm at 24 months (P=0.02). Overall, changes in bulb IMT were significantly correlated with changes in 25(OH)D (R=0.43, P=0.001). In multivariable regression models, larger increases in 25(OH)D were associated with greater IMT increases. In contrast to the findings in HIV+ subjects, among the healthy uninfected group (N=88), there were no differences in changes in IMT between the control vs. supplementation arms and no significant correlations between changes in 25(OH)D and changes in IMT.
A modest vitamin D3 dose of 18,000 IU/month given over 24 months resulted in significant decreases in carotid IMT compared to high monthly doses of 60,000 or 120,000 IU. These results suggest a potential for a less optimal effect of high-dose vitamin D supplementation in this population, an effect that was not seen in the parallel HIV-uninfected study. On-going analyses are underway to better understand these surprising findings.