Effect of High Dose Vitamin D Supplementation on HIV Latency

NCT03426592 | Completed Phase 2

• 1 other identifier: 2016.362
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Human Immunodeficiency Virus

Keywords

HIV; Inflammation; Vitamin D; Immunomodulation; Virus latency

Outcome Measures

Primary Outcomes (1)

• Change in total HIV DNA level

  The difference between the vitamin D and placebo arms in the mean change in frequency of total HIV DNA within CD4+ T cells from week 0 to week 24

  weeks 0 and 24

Secondary Outcomes (15)

• Change in other DNA markers of HIV persistence

  Weeks 0, 12, 24, 36

• Change in cell-associated HIV RNA

  Weeks 0, 12, 24, 36

• Change in proportion of immune cells

  Weeks 0, 12, 24, 36

• Change in T cell subset phenotype

  Weeks 0, 12, 24, 36

• Change in HIV-specific immunity

  Weeks 0, 12, 24, 36

Study Arms (2)

Vitamin D3, 10000 Intl Units Oral Capsule

ACTIVE COMPARATOR

Vitamin D3, 10000 Intl Units Oral Capsule, daily for 6 months

Drug: Vitamin D3, 10000 Intl Units Oral Capsule

Placebo oral capsule

PLACEBO COMPARATOR

Oleic acid capsule by mouth, daily for 6 months

Drug: Placebo oral capsule

Interventions

Vitamin D3, 10000 Intl Units Oral Capsule DRUG

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.

Also known as: Treatment Group

Vitamin D3, 10000 Intl Units Oral Capsule

Placebo oral capsule DRUG

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.

Also known as: Control Group

Placebo oral capsule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Melbourne: lead
• Melbourne Health: collaborator
• The Alfred: collaborator
• Melbourne Sexual Health Centre: collaborator
• University of Illinois at Chicago: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (4)

The Peter Doherty Institute for Infection and Immunity

Melbourne, Victoria, 3000, Australia

Location

The Alfred Hospital - Department of Infectious Diseases

Melbourne, Victoria, 3004, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Melbourne Sexual Health Centre

Melbourne, Victoria, 3053, Australia

Location

Related Publications (1)

• Pitman MC, Meagher N, Price DJ, Rhodes A, Chang JJ, Scher B, Allan B, Street A, McMahon JH, Rasmussen TA, Cameron PU, Hoy JF, Kent SJ, Lewin SR. Effect of high dose vitamin D3 on the HIV-1 reservoir: A pilot randomised controlled trial. J Virus Erad. 2023 Aug 29;9(3):100345. doi: 10.1016/j.jve.2023.100345. eCollection 2023 Sep.

  PMID: 37753336 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Inflammation

Interventions

Cholecalciferol; Control Groups

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Sharon Lewin, FRACP PhD

  The Peter Doherty Institute for Infection and Immunity, University of Melbourne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, The Peter Doherty Institute for Infection and Immunity

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: February 8, 2018
• Study Start: January 29, 2018
• Primary Completion: May 21, 2019
• Study Completion: May 21, 2019
• Last Updated: June 5, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4)