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. 2019 Apr 20;9(4):e028444.
doi: 10.1136/bmjopen-2018-028444.

"VSports在线直播" Effect of metformin on the size of the HIV reservoir in non-diabetic ART-treated individuals: single-arm non-randomised Lilac pilot study protocol

Jean-Pierre Routy  1   2 , Stéphane Isnard  1   3 , Vikram Mehraj  1   3 , Mario Ostrowski  4   5 , Nicolas Chomont  6 , Petronela Ancuta  6 , Rosalie Ponte  1   3 , Delphine Planas  6 , Franck P Dupuy  1   3 , Jonathan B Angel  7 ; Lilac Study Group
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Effect of metformin on the size of the HIV reservoir in non-diabetic ART-treated individuals: single-arm non-randomised Lilac pilot study protocol

Jean-Pierre Routy et al. BMJ Open. .

Abstract

Introduction: People living with HIV (PLWH) on antiretroviral therapy (ART) do not progress to AIDS. However, they still suffer from an increased risk of inflammation-associated complications. HIV persists in long-lived CD4+ T cells, which form the major viral reservoir. The persistence of this reservoir despite long-term ART is the major hurdle to curing HIV. Importantly, the size of the HIV reservoir is larger in individuals who start ART late in the course of infection and have a low CD4+/CD8+ ratio. HIV reservoir size is also linked to the levels of persistent inflammation on ART. Thus, novel strategies to reduce immune inflammation and improve the host response to control the HIV reservoir would be a valuable addition to current ART VSports手机版. Among the different strategies under investigation is metformin, a widely used antidiabetic drug that was recently shown to modulate T-cell activation and inflammation. Treatment of non-diabetic individuals with metformin controls inflammation by improving glucose metabolism and by regulating intracellular immunometabolic checkpoints such as the adenosin 5 monophosphate activated protein kinase and mammalian target of rapamycin, in association with microbiota modification. .

Methods and analysis: 22 PLWH on ART for more than 3 years, at high risk of inflammation or the development of non-AIDS events (low CD4+/CD8+ ratio) will be recruited in a clinical single-arm pilot study V体育安卓版. We will test whether supplementing ART with metformin in non-diabetic HIV-infected individuals can reduce the size of the HIV reservoir as determined by various virological assays. The expected outcome of this study is a reduction in both the size of the HIV reservoir and inflammation following the addition of metformin to ART, thus paving the way towards HIV eradication. .

Ethics and dissemination: Ethical approval: McGill university Health Centre committee number MP-37-2016-2456. Canadian Canadian Institutes of Health Research/Canadian HIV Trials Network (CTN) protocol CTNPT027. Results will be made available through publication in peer-reviewed journals and through the CTN website V体育ios版. .

Trial registration number: NCT02659306. VSports最新版本.

Keywords: HIV reservoir; immune activation; metformin; pilot study V体育平台登录. .

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VSports - Conflict of interest statement

Competing interests: J-PR has performed contract research and/or served on Advisory Boards for Gilead Sciences Canada, Merck Canada, Abbvie, ViiV Healthcare, Bristol Myers Squibb, Janssen, Argos Pharmaceuticals from InnaVirVax and has served on the Advisory Board of Theravectys. JBA has performed contract research and/or served on Advisory Boards for Gilead Sciences Canada, Merck Canada, Abbvie, ViiV Healthcare, Bristol Myers Squibb, Janssen and Argos Pharmaceuticals. MO has performed contract research and/or served on Advisory Boards for Gilead Sciences Canada, Merck Canada, Abbvie, ViiV Healthcare, Bristol Myers Squibb and Janssen V体育官网入口. NC has received research funding from Merck & Co. and from InnaVirVax and has served on the Advisory Board of Theravectys.

"V体育官网入口" Figures

Figure 1
Figure 1
Study design depicting study visits, intervention and laboratory assessments. ART, antiretroviral therapy; HbA1c, glycosylated haemoglobin; VL, viral load.
See this image and copyright information in PMC

References

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