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.