Effect of High Dose Vitamin D Supplementation on HIV Latency

• Status: Completed
• Trial end date: 2019-05-21
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Melbourne
• Collaborators: Melbourne Health; Melbourne Sexual Health Centre; National Institute of Allergy and Infectious Diseases (NIAID); The Alfred; University of Illinois at Chicago
• Treatments: Cholecalciferol; Ergocalciferols; Vitamin D; Vitamins

Criteria

Inclusion Criteria:

• Written informed consent obtained

• At least 18 years of age

• Documented HIV-1 infection

• Receiving combination antiretroviral therapy continuously for at least 3 years

• Viral load suppressed below 40 copies/mL, or below assay limit of quantification where limit of quantification is above 40 copies/mL, for at least 3 years (excluding single episodes of HIV viral load 40-500 copies/mL where subsequent viral load was below 40 copies/mL or below assay limit of quantification where limit of quantification is above 40 copies/mL)

• Viral load < 40 copies/ml at screening

• Screening 25-hydroxyvitamin D level within 12 months prior to recruitment between 50nM and 125nM

• Agreement not to take any vitamin D containing compounds other than study drug between screening and conclusion of the study

• Agreement not to have vitamin D level checked by a treating doctor during the study unless medically required

Exclusion Criteria:

• Any planned change to ART regimen within next 12 months (other than switching tenofovir disoproxil fumarate to tenofovir alafenamide)

• Known current acute or chronic hepatitis B, known current acute or chronic hepatitis C or positive HBsAg or HCV PCR in blood at screening

• Completion of curative treatment for HCV within 6 months prior to screening

• HIV-2 infection

• Any vitamin D supplementation from 6 months prior to the screening 25(OH) vitamin D test until study commencement (including multivitamins containing vitamin D and cod liver oil)

• Any medical indication for vitamin D supplementation, eg osteoporosis, renal impairment (estimated glomerular filtration rate < 60ml/minute), liver cirrhosis

• Chronic diarrhoea or fat malabsorption

• Body mass index (BMI >= 35)

• Current hypercalcaemia (corrected calcium greater than 2.60mM), current primary hyperparathyroidism or any history of nephrolithiasis

• Current hyperthyroidism

• History of sarcoidosis or active tuberculosis

• Grade 3 or 4 abnormalities in screening pathology laboratory tests not already excluded by the above criteria at the discretion of the Principal Investigator

• Hypersensitivity to vitamin D preparations

• Concurrent medication with adverse interactions with vitamin D (eg oral glucocorticoids, phenytoin, carbamazepine, barbiturates, rifampicin, rifabutin, St John's wort, thiazide diuretics, digoxin, ketoconazole, itraconazole, nefazodone, isoniazid, cholestyramine, aluminium hydroxide, aripiprazole, danazol, orlistat, perhexiline or sucralfate use) or possible such use within next 12 months

• Current interferon, immune checkpoint blocker, histone deacetylase inhibitor, oral vitamin A or other oral vitamin A analogue (eg acitretin, isotretinoin or tretinoin, also known as all-trans retinoic acid or ATRA) usage or possible use within next 12 months

• Current participation in another interventional HIV cure study

• Pregnancy or breast-feeding

• Participants of child-bearing potential unwilling to use at least one form of effective contraception (with failure rate <1%, eg hormonal contraception, intrauterine device, abstinence, tubal ligation or partner with vasectomy) from at least 2 weeks prior to study commencement until at least 4 weeks after discontinuation of all study medication

• Inability to consent

• Inability to speak English

• Medicare ineligibility

• Major medical or psychiatric illness or substance misuse that could in the opinion of the investigator impair adherence to the study protocol