Dataset Information

Effect of high dose vitamin D₃ on the HIV-1 reservoir: A pilot randomised controlled trial.

ABSTRACT:

Introduction

Antiretroviral therapy for people living with HIV-1 must be taken lifelong due to the persistence of latent virus in long-lived and proliferating CD4⁺ T cells. Vitamin D₃ is a steroidal gene transcription regulator which exerts diverse effects on immune and epithelial cells including reductions in CD4⁺ T cell proliferation and improvement in gut barrier integrity. We hypothesised that a high dose of vitamin D₃ would reduce the size of the HIV-1 reservoir by reducing CD4⁺ T cell proliferation.

Methods

We performed a randomised placebo-controlled trial evaluating the effect of 24 weeks of vitamin D₃ (10,000 international units per day) on the HIV-1 reservoir and immunologic parameters in 30 adults on antiretroviral therapy; participants were followed for 12 weeks post-treatment. The primary endpoint was the effect on total HIV-1 DNA at week 24. Parameters were assessed using mixed-effects models.

Results

We found no effect of vitamin D₃ on the change in total HIV-1 DNA from week 0 to week 24 relative to placebo. There were also no changes in integrated HIV-1 DNA, 2-long-terminal repeat (2-LTR) circles or cell-associated HIV-1 RNA. Vitamin D₃ induced a significant increase in the proportion of central memory CD4⁺ and CD8⁺ T cells, a reduction in the proportion of senescent CD8⁺ T cells and a reduction in the natural killer cell frequency at all time points including week 36, 12 weeks after the study drug cessation. At week 36, there was a significant reduction in total HIV-1 DNA relative to placebo and persistently elevated 25-hydroxyvitamin D levels. No significant safety issues were identified.

Conclusions

Vitamin D₃ administration had a significant impact on the T cell differentiation but overall effects on the HIV-1 reservoir were limited and a reduction in HIV-1 DNA was only seen following cessation of the study drug. Additional studies are required to determine whether the dose and duration of vitamin D₃ can be optimised to promote a continued depletion of the HIV-1 reservoir over time.

Trial registration

ClinicalTrials.gov NCT03426592.

SUBMITTER: Pitman MC

PROVIDER: S-EPMC10518338 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Effect of high dose vitamin D3 on the HIV-1 reservoir: A pilot randomised controlled trial.

Pitman Matthew C MC Meagher Niamh N Price David J DJ Rhodes Ajantha A Chang J Judy JJ Scher Barbara B Allan Brent B Street Alan A McMahon James H JH Rasmussen Thomas A TA Cameron Paul U PU Hoy Jennifer F JF Kent Stephen J SJ Lewin Sharon R SR

Journal of virus eradication 20230829 3

<h4>Introduction</h4>Antiretroviral therapy for people living with HIV-1 must be taken lifelong due to the persistence of latent virus in long-lived and proliferating CD4+ T cells. Vitamin D3 is a steroidal gene transcription regulator which exerts diverse effects on immune and epithelial cells including reductions in CD4+ T cell proliferation and improvement in gut barrier integrity. We hypothesised that a high dose of vitamin D3 would reduce the size ...[more]

PMID: 37753336

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