INTERFERON AND RIBAVIRIN COMBINATION THERAPY INCREASES VITAMIN D LEVELS
A. Soumekh, K. Bichoupan, C. Constable, P. Benedict, M.L.C. Vachon, D.T. Dieterich, A.D. Branch
Mount Sinai School of Medicine
Background: Emerging data suggest that high 25(OH)D levels improve treatment outcomes. Ribavirin's mechanism of action is unknown. We hypothesized that treatment raises 25(OH)D levels, thereby enhancing efficacy. Methods: Subjects had HIV/HCV co-infection. All gave informed consent and completed at least 24 weeks of HRN-004, a multi-center retreatment trial of peg-IFN-alpha-2a/ribavirin. The Diasorin assay determined 25(OH)D in baseline (N=88) and 24-week samples (N=70). Changes in 25(OH)D and calcium were analyzed using the Wilcoxon Signed Ranks Test. Results: Most subjects were male; 86% had genotype 1 HCV; 15% (N=13) achieved an SVR. As predicted, 25(OH)D levels increased significantly during treatment, by a median of 2.20 ng/ml, p=0.037. Serum calcium, corrected for albumin, decreased significantly, by a median of -0.13 mg/dl, p=0.037, and fell below the lower-limit-of-normal in 12 subjects. In a multivariate logistic regression model, baseline 25(OH)D >18 ng/ml was the only variable significantly associated with SVR (OR, 5.077, p=0.043). Serum 25(OH)D and genotype were the only factors associated with cEVR (OR, 4.251, p=0.024; OR 12.105, P=0.005, respectively). Changes in 25(OH)D were significantly associated with EVR (OR, 1.059, p=0.050). Conclusions: We report two important findings about IFN/RBV treatment: Vitamin D levels increase, and calcium levels fall. Because treatment success is positively associated with vitamin D increases, the on-treatment increase in 25(OH)D may be a newly-discovered component of drug action. The drop in calcium may have adverse consequences, e.g., on bone. The potential of vitamin D and calcium supplements to improve outcome and to protect bone merits investigation (DA031095;DK090317).