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Background: There is substantial heterogeneity in both the rate of increase and plateau of CD4+ T cell count (CD4) in response to effective therapy (HAART) initiation. Since vitamin D can have immunoregulatory function, we investigated whether higher serum levels of 25 hydroxyvitamin D (25OHD) were associated with improved CD4 recovery following HAART initiation in HIV-infected men who have sex with men (MSM).
Methods: 25OHD level was measured following HAART initiation in 636 HIV-infected MSM with at least one post-HAART CD4 measurement. Anchoring at HAART start, CD4 over time was modeled using an exponential decay nonlinear mixed effects model with three random effects for the intercept, rate of increase and plateau. We assessed the effect of higher seasonally-adjusted post-HAART 25OHD levels on the rate of increase and plateau of CD4, controlling for age, pre-HAART CD4 nadir, and race.
Results: At HAART initiation, the median age was 42.3 years, the median pre-HAART CD4 nadir was 260 cells/ml, and 25.8% of men were of black race. The median post-HAART 25OHD level was 22.6 ng/ml (interquartile range [IQR]: 16.1, 29.9; 56.4 nmol/L) assessed at median time of 2.2 years (IQR: 1.7, 2.4) after initiation. The overall predicted median CD4 plateau was 523 cells/mm3 (IQR: 343, 751) and the median time to CD4 plateau was 11.3 years. A higher post-HAART 25OHD level was significantly associated with both the rate of CD4 increase and plateau, with a 10% faster rate (p< 0.01) and a 3% higher plateau (p< 0.01) per 10 ng/ml (25 nmol/L) 25OHD. The Figure shows the expected difference in CD4 rebound comparing the 75%ile of 25OHD level in the cohort to the 25%ile.

Adjusted effect of higher 25OHD levels on CD4+ T cell count rebound following HAART initiation
[Adjusted effect of higher 25OHD levels on CD4+ T cell count rebound following HAART initiation]


Conclusions: Vitamin D levels may modestly augment the extent of quantitative CD4 increase following HAART initiation. Interventional trials are needed to determine whether supplementation at HAART initiation provides consequential clinical benefits.

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