Matthew C. Pitman , Niamh Meagher , David J. Price , Ajantha Rhodes , J. Judy Chang , Barbara Scher , Brent Allan , Alan Street , James H. McMahon , Thomas A. Rasmussen , Paul U. Cameron , Jennifer F. Hoy , Stephen J. Kent , Sharon R. Lewin
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We hypothesised that a high dose of vitamin D<sub>3</sub> would reduce the size of the HIV-1 reservoir by reducing CD4<sup>+</sup> T cell proliferation.</p></div><div><h3>Methods</h3><p>We performed a randomised placebo-controlled trial evaluating the effect of 24 weeks of vitamin D<sub>3</sub> (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.</p></div><div><h3>Results</h3><p>We found no effect of vitamin D<sub>3</sub> 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 D<sub>3</sub> induced a significant increase in the proportion of central memory CD4<sup>+</sup> and CD8<sup>+</sup> T cells, a reduction in the proportion of senescent CD8<sup>+</sup> 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.</p></div><div><h3>Conclusions</h3><p>Vitamin D<sub>3</sub> 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 D<sub>3</sub> can be optimised to promote a continued depletion of the HIV-1 reservoir over time.</p></div><div><h3>Trial registration</h3><p>ClinicalTrials.gov <span>NCT03426592</span><svg><path></path></svg>.</p></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"9 3","pages":"Article 100345"},"PeriodicalIF":3.5000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of high dose vitamin D3 on the HIV-1 reservoir: A pilot randomised controlled trial\",\"authors\":\"Matthew C. Pitman , Niamh Meagher , David J. Price , Ajantha Rhodes , J. Judy Chang , Barbara Scher , Brent Allan , Alan Street , James H. McMahon , Thomas A. Rasmussen , Paul U. Cameron , Jennifer F. Hoy , Stephen J. Kent , Sharon R. Lewin\",\"doi\":\"10.1016/j.jve.2023.100345\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>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<sup>+</sup> T cells. Vitamin D<sub>3</sub> is a steroidal gene transcription regulator which exerts diverse effects on immune and epithelial cells including reductions in CD4<sup>+</sup> T cell proliferation and improvement in gut barrier integrity. We hypothesised that a high dose of vitamin D<sub>3</sub> would reduce the size of the HIV-1 reservoir by reducing CD4<sup>+</sup> T cell proliferation.</p></div><div><h3>Methods</h3><p>We performed a randomised placebo-controlled trial evaluating the effect of 24 weeks of vitamin D<sub>3</sub> (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.</p></div><div><h3>Results</h3><p>We found no effect of vitamin D<sub>3</sub> 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 D<sub>3</sub> induced a significant increase in the proportion of central memory CD4<sup>+</sup> and CD8<sup>+</sup> T cells, a reduction in the proportion of senescent CD8<sup>+</sup> 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. 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Additional studies are required to determine whether the dose and duration of vitamin D<sub>3</sub> can be optimised to promote a continued depletion of the HIV-1 reservoir over time.</p></div><div><h3>Trial registration</h3><p>ClinicalTrials.gov <span>NCT03426592</span><svg><path></path></svg>.</p></div>\",\"PeriodicalId\":17552,\"journal\":{\"name\":\"Journal of Virus Eradication\",\"volume\":\"9 3\",\"pages\":\"Article 100345\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2023-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Virus Eradication\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2055664023000316\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Virus Eradication","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2055664023000316","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Effect of high dose vitamin D3 on the HIV-1 reservoir: A pilot randomised controlled trial
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.
期刊介绍：
The Journal of Virus Eradication aims to provide a specialist, open-access forum to publish work in the rapidly developing field of virus eradication. The Journal covers all human viruses, in the context of new therapeutic strategies, as well as societal eradication of viral infections with preventive interventions.
The Journal is aimed at the international community involved in the prevention and management of viral infections. It provides an academic forum for the publication of original research into viral reservoirs, viral persistence and virus eradication and ultimately development of cures.
The Journal not only publishes original research, but provides an opportunity for opinions, reviews, case studies and comments on the published literature. It focusses on evidence-based medicine as the major thrust in the successful management of viral infections.The Journal encompasses virological, immunological, epidemiological, modelling, pharmacological, pre-clinical and in vitro, as well as clinical, data including but not limited to drugs, immunotherapy and gene therapy. It is an important source of information on the development of vaccine programs and preventative measures aimed at virus eradication.
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