Effect of high dose vitamin D3 on the HIV-1 reservoir : A pilot randomised controlled trial
© 2023 The Authors..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Journal of virus eradication - 9(2023), 3 vom: 15. Sept., Seite 100345 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pitman, Matthew C [VerfasserIn] |
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| Links: |
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| Themen: |
Cell proliferation |
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| Anmerkungen: |
Date Revised 28.09.2023 published: Electronic-eCollection ClinicalTrials.gov: NCT03426592 Citation Status Publisher |
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| doi: |
10.1016/j.jve.2023.100345 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362496633 |
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| 041 | |a eng | ||
| 100 | 1 | |a Pitman, Matthew C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effect of high dose vitamin D3 on the HIV-1 reservoir |b A pilot randomised controlled trial |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 28.09.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a ClinicalTrials.gov: NCT03426592 | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2023 The Authors. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a Trial registration: ClinicalTrials.gov NCT03426592 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cell proliferation | |
| 650 | 4 | |a DNA | |
| 650 | 4 | |a HIV | |
| 650 | 4 | |a Randomised controlled trial | |
| 650 | 4 | |a T-lymphocytes | |
| 650 | 4 | |a Vitamin D | |
| 700 | 1 | |a Meagher, Niamh |e verfasserin |4 aut | |
| 700 | 1 | |a Price, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Rhodes, Ajantha |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, J Judy |e verfasserin |4 aut | |
| 700 | 1 | |a Scher, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Allan, Brent |e verfasserin |4 aut | |
| 700 | 1 | |a Street, Alan |e verfasserin |4 aut | |
| 700 | 1 | |a McMahon, James H |e verfasserin |4 aut | |
| 700 | 1 | |a Rasmussen, Thomas A |e verfasserin |4 aut | |
| 700 | 1 | |a Cameron, Paul U |e verfasserin |4 aut | |
| 700 | 1 | |a Hoy, Jennifer F |e verfasserin |4 aut | |
| 700 | 1 | |a Kent, Stephen J |e verfasserin |4 aut | |
| 700 | 1 | |a Lewin, Sharon R |e verfasserin |4 aut | |
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