NCT03426592

Effect of High Dose Vitamin D Supplementation on HIV Latency

Effect of High Dose Vitamin D Supplementation on HIV Latency: A Pilot Randomized Controlled Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: University of Melbourne · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

HIV persists despite antiretroviral therapy (ART) and is associated with chronic inflammation. This inflammation is thought to prevent an effective immune response against the virus and is mediated at least in part by gut epithelial permeability and microbial translocation. HIV accumulates preferentially within Th17 cells with time on ART; these memory CD4+ T cells are highly susceptible to HIV infection and are concentrated within the gut. Vitamin D promotes gut epithelial integrity in animal models and exerts anti-inflammatory effects on the human immune system including down-modulation of Th17 cell frequency. This study will evaluate whether high dose vitamin D is able to reduce immune activation and Th17 cell frequency, to improve gut barrier integrity and the gut microbiome and reduce HIV persistence in participants on long-term suppressive ART.

Detailed description

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.

Conditions

• Human Immunodeficiency Virus

Interventions

Type	Name	Description
DRUG	Vitamin D3, 10000 Intl Units Oral Capsule	Vitamin D capsule. Over-encapsulated to mimic placebo oral capsule. Eligible study participants will be randomized 1:1 to vitamin D or placebo one capsule daily from week 0 to week 24. All participants will be advised to achieve 1 gram daily dietary calcium intake whilst on study. Blood and urine will be taken at 0, 12, 24 and 36 weeks to evaluate the primary and secondary endpoints. Rectal swabs will be taken at 0, 24 and 36 weeks. All participants will continue antiretroviral therapy throughout the study.
DRUG	Placebo oral capsule	Capsule containing oleic acid. Over-encapsulated to mimic vitamin D3 capsule. Eligible study participants will be randomized 1:1 to vitamin D or placebo one capsule daily from week 0 to week 24. All participants will be advised to achieve 1 gram daily dietary calcium intake whilst on study. Blood and urine will be taken at 0, 12, 24 and 36 weeks to evaluate the primary and secondary endpoints. Rectal swabs will be taken at 0, 24 and 36 weeks. All participants will continue antiretroviral therapy throughout the study.

Timeline

• Start date: 2018-01-29
• Primary completion: 2019-05-21
• Completion: 2019-05-21
• First posted: 2018-02-08
• Last updated: 2019-06-05

Locations

4 sites across 1 country: Australia