Effect of High Dose Vitamin D Supplementation on HIV Latency

The major barrier to a cure for HIV infection is the persistence of latently infected CD4+ T cells on antiretroviral therapy (ART). HIV is concentrated in vivo in Th17 cells in blood and the gastrointestinal tract. Th17 cells are critical mediators of mucosal immunity against bacteria and fungi and are rapidly depleted in the gut following HIV acquisition with subsequent gut epithelial permeability, microbial translocation and ensuing chronic inflammation which is not completely reversed on ART. Such inflammation may contribute to HIV persistence by potentiating T cell proliferation and thereby clonal expansion of infected cells, by exacerbating CD8+ T cell exhaustion and potentially by promoting viral replication despite ART. Vitamin D has pleiotropic effects on the immune system including directing naïve CD4+ T cells away from the Th17 phenotype toward an anti-inflammatory regulatory T cell phenotype. It may also have beneficial effects on dendritic cell and CD8+ T cell immunity. Furthermore, vitamin D has been shown in animal models to strengthen gut epithelial integrity and in healthy volunteers to promote a more diverse gut microbiome. The investigators plan to perform a pilot randomized double-blind placebo-controlled trial of high dose vitamin D supplementation in HIV-infected participants on suppressive ART and to determine its effect on immune activation, Th17 cell frequency, gut barrier integrity, the gut microbiome and HIV persistence.