Vitamin D Status Impacts Genital Mucosal Immunity and Markers of HIV-1 Susceptibility in Women

Abstract

While vitamin D insufficiency is known to impact a multitude of health outcomes, including HIV-1, little is known about the role of vitamin D-mediated immune regulation in the female reproductive tract (FRT). We performed a pilot clinical study of 20 women with circulating 25(OH)D levels <62.5 nmol/L. Participants were randomized into either weekly or daily high-dose oral vitamin D supplementation groups. In addition to serum vitamin D levels, genital mucosal endpoints, including soluble mediators, immune cell populations, gene expression, and ex vivo HIV-1 infection, were assessed. While systemic vitamin D levels showed a significant increase following supplementation, these changes translated into modest effects on the cervicovaginal factors studied. Paradoxically, post-supplementation vitamin D levels were decreased in cervicovaginal fluids. Given the strong correlation between vitamin D status and HIV-1 infection and the widespread nature of vitamin D deficiency, further understanding of the role of vitamin D immunoregulation in the female reproductive tract is important.

Keywords: HIV-1 susceptibility; immune regulation; vitamin D supplementation.

Figure 1

Vitamin D supplementation increased mean serum 25(OH)D concentration to above adequate levels >75 nmol/L (30 ng/mL). Women were sampled before and after 8 weeks of either weekly (n = 10) or daily (n = 10) high-dose vitamin D. (A) Grouped mean (± SD) serum 25(OH)D concentrations from both weekly and daily arms (n = 20) before and after vitamin D supplementation. (B) Mean (± SD) serum 25(OH)D concentrations from weekly and daily supplementation arms. * Denotes significant difference between baseline and treatment; ** denotes significant difference between daily and weekly supplementation groups following treatment.

Figure 2

Quantitative real-time PCR was performed on RNA isolated from vaginal biopsies taken at V2 baseline versus V3 post-supplementation. The relative changes in gene expression were calculated using the 2-ΔΔCt method, and expressed as positive or negative fold change compared to V2 with 1 or -1 as reference points, respectively.