Associations between 25-hydroxyvitamin D and immunologic, metabolic, inflammatory markers in treatment-naive HIV-infected persons: the ANRS CO9 «COPANA» cohort study

Camille Legeai, Corinne Vigouroux, Jean-Claude Souberbielle, Olivier Bouchaud, Faroudy Boufassa, Jean-Philippe Bastard, Robert Carlier, Jacqueline Capeau, Cécile Goujard, Laurence Meyer, Jean-Paul Viard, ANRS-COPANA Cohort Study Group, Christine Rouzioux, Véronique Avettand-Fenoël, Claudine Duvivier, Fatima Touam, Rodolphe Thiébaut, Laurence Meyer, Faroudy Boufassa, Marie-Aline Charles, Rosemary Dray-Spira, Camille Legeai, Badra Boumaza, Abdellatif Essabbani, Remonie Seng, Gilles Pialoux, Laurence Slama, Philippe Bonnard, Catherine Chakvetadze, Thomas L' Yavanc, Jacqueline Capeau, Corinne Vigouroux, Soraya Fellahi, Jean-Philippe Bastard, Jean-Paul Viard, Aline Maignan, Alain Sobel, Eric Oksenhendler, Laurence Gérard, Daniel Séréni, Caroline Lascoux-Combe, Claire Pintado, Olivier Taulera, Le Van Dien, Jeannine Delgado, Sylvie Parlier, Jean-Michel Molina, Thierry Saint-Marc, Samuel Ferret, Juliette Pavie, Jean-François Bergmann, Agathe Rami, Maguy Parrinello, Pierre-Marie Girard, Bénédicte Lefebvre, Alysa Krain, Catherine Lupin, Serge Herson, Hassiba Remidi, Malik Iguertsira, Smaïl Nafissa, Anne Simon, Nadia Edeb, Dominique Salmon-Céron, Loïc Guillevin, Tassadit Tahi, Marie Pierre Pietri, Laurence Weiss, Marie-Laure Lucas, Magalie Ptak, Delphine Tisne-Dessus, Christelle Jalbert, Patrick Yeni, Golriz Pahlavan, Bao Phung, Nadia El-Alami Talbi, Zahia Ramani, Giovanna Catalano, Julia Zelie, Bilguissa Diallo, Cindy Godard, François Boué, Véronique Chambrin, Imad kansau, Marie-Thérèse Rannou, Mariem Raho, Dominique Bornarel, Hélène Schoen, Robert Carlier, Bruno Fantin, Agnès Uludag, Ali Tadlaoui, Caroline Poder, Robin Dhote, Michelle Bentata, Tuna Lukiana, Patricia Honoré, Olivier Bouchaud, Xuan Tuyet, Jean-François Delfraissy, Cécile Goujard, Fabrice Chaix, Erwan Fourn, Katia Bourdic, Yves Levy, Cécile Dumont, André Cabié, Christelle Baringthon, Isabelle Poizot-Martin, Geneviève Fabre, Olivia Zaegel-Faucher, Alena Ivanova, Caroline Debreux, Jacques Moreau, Martine Schlossers, Saadia Mokhtari, Evelyne Van Der Gheynst, Marie-Christine Thiebaut-Drobacheff, Adeline Foltzer, Catherine Bourdeaux, Bruno Hoen, Jean-François Faucher, Helder Gil, Didier Neau, Charles Cazanave, Thierry Pistone, Michel Dupon, Jean-Marie Ragnaud, Isabelle Raymond, Laetitia Lacaze-Buzy, Caroline Palacin, Philippe Morlat, Sabrina Caldato, Isabelle Louis, Mojgan Hessamfar, Jacques Reynes, Claude Crisol, Vincent Baillat, Corinne Merle De Boever, Christine Tramoni, Louis Bernard, Pascale Nau, Gaëlle Sajole, Carine Sèvre, Antoine Soufflet, Patrick Guadagnin, Frédéric Bastides, Patrick Choutet, François Raffi, Olivier Mounoury, Véronique Reliquet, Delphine Brosseau, Thierry May, Amandine Briault, Simone Wassoumbou, Antoine Chéret, Séverine Bonne, Yazdan Yazdanpanah, Thomas Huleux, Emmanuelle Aïssi, David Rey, Christine Cheneau, Mahsa Mohseni Zadeh, Aurélie Richard, Gilles Blaison, Martin Martinot, Anne Pachard, Djamila Makhloufi, François Jeanblanc, Jean-Louis Touraine, Laurent Cotte, Claude Augustin-Normand, Joseph Koffi Patrick Miailhes, Sophie Pailhes, Isabelle Schlienger, Philippe Perré, Jean Luc Esnault, Isabelle Suaud, Camille Legeai, Corinne Vigouroux, Jean-Claude Souberbielle, Olivier Bouchaud, Faroudy Boufassa, Jean-Philippe Bastard, Robert Carlier, Jacqueline Capeau, Cécile Goujard, Laurence Meyer, Jean-Paul Viard, ANRS-COPANA Cohort Study Group, Christine Rouzioux, Véronique Avettand-Fenoël, Claudine Duvivier, Fatima Touam, Rodolphe Thiébaut, Laurence Meyer, Faroudy Boufassa, Marie-Aline Charles, Rosemary Dray-Spira, Camille Legeai, Badra Boumaza, Abdellatif Essabbani, Remonie Seng, Gilles Pialoux, Laurence Slama, Philippe Bonnard, Catherine Chakvetadze, Thomas L' Yavanc, Jacqueline Capeau, Corinne Vigouroux, Soraya Fellahi, Jean-Philippe Bastard, Jean-Paul Viard, Aline Maignan, Alain Sobel, Eric Oksenhendler, Laurence Gérard, Daniel Séréni, Caroline Lascoux-Combe, Claire Pintado, Olivier Taulera, Le Van Dien, Jeannine Delgado, Sylvie Parlier, Jean-Michel Molina, Thierry Saint-Marc, Samuel Ferret, Juliette Pavie, Jean-François Bergmann, Agathe Rami, Maguy Parrinello, Pierre-Marie Girard, Bénédicte Lefebvre, Alysa Krain, Catherine Lupin, Serge Herson, Hassiba Remidi, Malik Iguertsira, Smaïl Nafissa, Anne Simon, Nadia Edeb, Dominique Salmon-Céron, Loïc Guillevin, Tassadit Tahi, Marie Pierre Pietri, Laurence Weiss, Marie-Laure Lucas, Magalie Ptak, Delphine Tisne-Dessus, Christelle Jalbert, Patrick Yeni, Golriz Pahlavan, Bao Phung, Nadia El-Alami Talbi, Zahia Ramani, Giovanna Catalano, Julia Zelie, Bilguissa Diallo, Cindy Godard, François Boué, Véronique Chambrin, Imad kansau, Marie-Thérèse Rannou, Mariem Raho, Dominique Bornarel, Hélène Schoen, Robert Carlier, Bruno Fantin, Agnès Uludag, Ali Tadlaoui, Caroline Poder, Robin Dhote, Michelle Bentata, Tuna Lukiana, Patricia Honoré, Olivier Bouchaud, Xuan Tuyet, Jean-François Delfraissy, Cécile Goujard, Fabrice Chaix, Erwan Fourn, Katia Bourdic, Yves Levy, Cécile Dumont, André Cabié, Christelle Baringthon, Isabelle Poizot-Martin, Geneviève Fabre, Olivia Zaegel-Faucher, Alena Ivanova, Caroline Debreux, Jacques Moreau, Martine Schlossers, Saadia Mokhtari, Evelyne Van Der Gheynst, Marie-Christine Thiebaut-Drobacheff, Adeline Foltzer, Catherine Bourdeaux, Bruno Hoen, Jean-François Faucher, Helder Gil, Didier Neau, Charles Cazanave, Thierry Pistone, Michel Dupon, Jean-Marie Ragnaud, Isabelle Raymond, Laetitia Lacaze-Buzy, Caroline Palacin, Philippe Morlat, Sabrina Caldato, Isabelle Louis, Mojgan Hessamfar, Jacques Reynes, Claude Crisol, Vincent Baillat, Corinne Merle De Boever, Christine Tramoni, Louis Bernard, Pascale Nau, Gaëlle Sajole, Carine Sèvre, Antoine Soufflet, Patrick Guadagnin, Frédéric Bastides, Patrick Choutet, François Raffi, Olivier Mounoury, Véronique Reliquet, Delphine Brosseau, Thierry May, Amandine Briault, Simone Wassoumbou, Antoine Chéret, Séverine Bonne, Yazdan Yazdanpanah, Thomas Huleux, Emmanuelle Aïssi, David Rey, Christine Cheneau, Mahsa Mohseni Zadeh, Aurélie Richard, Gilles Blaison, Martin Martinot, Anne Pachard, Djamila Makhloufi, François Jeanblanc, Jean-Louis Touraine, Laurent Cotte, Claude Augustin-Normand, Joseph Koffi Patrick Miailhes, Sophie Pailhes, Isabelle Schlienger, Philippe Perré, Jean Luc Esnault, Isabelle Suaud

Abstract

Objectives: Low 25(OH)D has been associated with dyslipidemia, insulin resistance and inflammation in both general and HIV-infected (mostly treated) populations. We investigated these associations in antiretroviral-naïve HIV-infected persons.

Design: We measured plasma 25(OH)D, metabolic, immunologic and inflammatory markers in 355 persons (204 Whites, 151 Blacks) at enrollment in the ANRS COPANA cohort.

Methods: 25(OH)D levels were categorized <10 ng/mL (severe deficiency) and <20 ng/mL (deficiency). Statistical analyses were adjusted for sampling season, ethnicity and the interaction between season and ethnicity.

Results: 25(OH)D insufficiency (<30 ng/mL), deficiency (<20 ng/mL) and severe deficiency (<10 ng/mL) were highly prevalent (93%, 67% and 24% of patients, respectively). Blacks had significantly lower 25(OH)D than Whites (median: 13 vs. 17 ng/mL, P<0.001), with markedly less pronounced seasonal variation. Smoking and drinking alcohol were associated with having a 25 OHD level<10 ng/mL. In patients with 25(OH)D<10 ng/mL, the proportion of persons with a CD4 count<100/mm(3) was higher than in patients with 25(OH)D≥10 ng/mL (18.8% vs. 10.7%, P = 0.04). Persons with 25 OHD<10 ng/mL had higher levels of hsCRP (1.60 mg/L [IQR: 0.59-5.76] vs. 1.27 mg/L [0.58-3,39], P = 0.03) and resistin (16.81 ng/L [IQR: 13.82-25.74] vs. 11.56 ng/L [IQR: 8.87-20.46], P = 0.02), and, among Blacks only, sTNFR2 (2.92 ng/mL [2.31-4.13] vs. 2.67 ng/mL, [1.90-3.23], P = 0.04). The strength and significance of the association between CD4<100/mm(3) and 25 OHD<10 ng/mL were reduced after adjustment on sTNFR1, sTNFR2, and hsCRP levels. In multivariate analysis, a CD4 count <100/mm(3), resistin concentration and smoking were independently associated with 25(OH)D<10 ng/mL.

Conclusions: Severe vitamin D deficiency was associated with low CD4 counts and increased markers of inflammation in ARV-naïve HIV-infected persons.

Conflict of interest statement

Competing Interests: Jean-Paul Viard has received travel grants, consultancy fees, honoraria or study grants from Abbott, Boehringer-Ingelheim, Bristol-Myers-Squibb, Gilead Sciences, Glaxo-Smith-Kline, Janssen-Cilag, Merck-Sharp & Dohme-Chibret. None of these were related to the present work, and this does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. 25(OH)D plasma levels according to…
Figure 1. 25(OH)D plasma levels according to sampling dates in White and Black patients.
Jan: January; Jul: July O and X symbols depict individual 25(OH)D plasma levels in White and Black patients, respectively.

References

    1. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357: 266–281.
    1. Norman AW, Bouillon R (2010) Vitamin D nutritional policy needs a vision for the future. Exp Biol Med 235: 1034–1045.
    1. Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, et al. (2010) Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: recommendations for clinical practice. Autoimmunity Rev 9: 709–715.
    1. Adams JS, Hewison M (2010) Update in vitamin D. J Clin Endocrinol Metab. 95: 471–478.
    1. Pilz S, Dobnig H, Nijpels G, Heine RJ, Stehouwer CD, et al. (2009) Vitamin D and mortality in older men and women. Clin Endocrinol 71: 666–672.
    1. Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, et al. (2008) Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med 168: 1340–1349.
    1. Joergensen C, Gall MA, Schmedes A, Tarnow L, Parving HH, et al. (2010) Vitamin D levels and mortality in type 2 diabetes. Diabetes Care 33: 2238–2243.
    1. Ng K, Meyerhardt JA, Wu K, Feskanich D, Hollis BW, et al. (2008) Circulating 25-hydroxyvitamin D levels and survival in patients with colorectal cancer. J Clin Oncol 26: 2984–2991.
    1. Zittermann A, Schleithoff SS, Götting C, Fuchs U, Kuhn J, et al. (2009) Calcitriol deficiency and 1-year mortality in cardiac transplant recipients. Transplantation 87: 118–124.
    1. Pilz S, Iodice S, Zittermann A, Grant WB, Gandini S (2011) Vitamin D status and mortality risk in CKD: a meta-analysis of prospective studies. Am J Kidney Dis 58: 374–382.
    1. Dao CN, Patel P, Overton ET, Rhame F, Pals SL, et al. (2011) Low vitamin D among HIV-infected adults: prevalence of and risk factors for low vitamin D levels in a cohort of HIV-infected adults and comparison to prevalence among adults in the US general population. Clin Infect Dis 52: 396–405.
    1. Childs K, Welz T, Samarawickrama A, Post FA (2012) Effects of vitamin D deficiency and combination antiretroviral therapy on bone in HIV-positive patients. AIDS 26: 253–262.
    1. Boxer RS, Dauser DA, Walsh SJ, Hager WD, Kenny AM (2008) The association between vitamin D and inflammation with the 6-minute walk and frailty in patients with heart failure. J Am Geriatr Soc 56: 454–461.
    1. Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, et al. (2006) Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure : a double-blind, randomized, placebo-controlled study. Am J Clin Nutr 83: 754–759.
    1. Hyppönen E, Berry D, Cortina-Borja M, Power C (2010) 25-hydroxyvitamin D and pre-clinical alterations in inflammatory and hemostatic markers : a cross sectional analysis in the 1958 British birth cohort. PLoS ONE 5 5: e10801 doi/
    1. von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, et al. (2010) Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nature Immunol 11: 344–349.
    1. Mehta S, Giovanucci E, Mugusi FM, Spiegelman D, Aboud S, et al. (2010) Vitamin D status of HIV-infected women and its association with HIV disease progression, anemia, and mortality. PLoS ONE 5(1): e8770 doi:
    1. Viard JP, Souberbielle JC, Kirk O, Knysz B, Losso M, et al. (2011) Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study. AIDS 25: 1305–1315.
    1. Sudfeld CR, Wang M, Aboud S, Giovannucci EL, Mugusi FM, et al. (2012) Vitamin D and HIV progression among Tanzanian adults initiating antiretroviral Therapy. PLoS ONE 7(6): e40036 doi:
    1. Ross AC, Judd S, Kumari M, Hileman C, Storer N, et al. (2011) Vitamin D is linked to carotid intima-media thickness and immune reconstitution in HIV-positive individuals. Antiviral Ther 16: 555–563.
    1. Aziz M, Livak B, Burke-Miller J, French A, Glesby MJ, et al. (2013) Vitamin D insufficiency may impair CD4 recovery among Women’s Interagency HIV Study (WIHS) participants with advanced disease on HAART. AIDS 27: 573–578.
    1. Vescini F, Cozzi-Lepri A, Borderi M, Re MC, Maggiolo F, et al. (2011) Prevalence of hypovitaminosis D and factors associated with vitamin D deficiency and morbidity among HIV-infected patients enrolled in a large Italian cohort. J Acquir Immune Defic Syndr 58: 163–72.
    1. Sudfeld CR, Giovanucci EL, Isanaka S, Aboud S, Mugusi FM, et al. (2013) Vitamin D status and incidence of pulmonary tuberculosis, opportunistic infections, and wasting among Tanzanian adults initiating antiretroviral therapy. J Infect Dis 207: 1370–1378.
    1. Hammond E, McKinnon E, Glendenning P, Williams R, Mallal S, et al. (2012) Association between 25-OH vitamin D and insulin is independent of lipoatrophy in HIV. Clin Endocrinol (Oxf) 76: 201–206.
    1. Szep Z, Guaraldi G, Shah SS, Lo Re 3rd V, Ratcliffe SJ, et al. (2011) Vitamin D deficiency is associated with type 2 diabetes mellitus in HIV infection. AIDS 25: 525–529.
    1. Choi AI, Lo JC, Mulligan K, Schnell A, Kalapus SC, et al. (2011) Association of vitamin D insufficiency with carotid intima-media thickness in HIV-infected persons. Clin Infect Dis 52: 941–944.
    1. Shikuma CM, Seto T, Liang CY, Bennett K, DeGruttola V, et al. (2012) Vitamin D levels and markers of arterial dysfunction. AIDS Res Human Retroviruses 28: 793–797.
    1. Lai H, Gerstenblith G, Fishman EK, Brinker J, Kickler T, et al. (2012) Vitamin D deficiency is associated with silent coronary artery disease in cardiovascularly asymptomatic African Americans with HIV infection. Clin Infect Dis 54: 1747–1755.
    1. Boufassa F, Goujard C, Viard JP, Carlier R, Lefebvre B, et al. (2012) Immune deficiency could be an early risk factor for altered insulin sensitivity in antiretroviral-naïve HIV-1-infected patients; the ANRS COPANA cohort. Antiviral Ther 17: 91–100.
    1. Baker JV, Lundgren JD (2011) Cardiovascular implications from untreated human immunodeficiency virus infection. Eur Heart J 32: 945–951.
    1. Lang S, Mary-Krause M, Cotte L, Gilquin J, Partisani M, et al. (2010) Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus–infected patients. A case-control study nested within the French hospital database on HIV ANRS cohort CO4. Arch Intern Med. 170: 1228–1238.
    1. Nixon DE, Landay AL (2010) Biomarkers of immune dysfunction in HIV. Curr Opin HIV AIDS 5: 498–503.
    1. Feingold KR, Krauss RM, Pang M, Doerrler W, Jensen P, et al. (1993) The hypertriglyceridemia of acquired immunodeficiency syndrome is associated with an increased prevalence of low density lipoprotein subclass pattern B. J Clin Endocrinol Metab. 76: 1423–1427.
    1. Allavena C, Delpierre C, Cuzin L, Rey D, Viget N, et al. (2012) High frequency of vitamin D deficiency in HIV-infected patients: effects of HIV-related factors and antiretroviral drugs. J Antimicrob Chemother 67: 2222–2230.
    1. Schwartz DR, Lazar MA (2011) Human resistin: found in translation from mouse to man. Trends Endocrinol Metab 22: 259–265.
    1. Coussens AK, Wilkinson RJ, Hanifa Y, Nikolayevskyy V, Elkington PT, et al. (2012) Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proc Natl Acad Sci USA 109: 15449–15454.
    1. Jorde R, Grimnes G (2011) Vitamin D and metabolic health with special reference to the effects of vitamin D on serum lipids. Prog Lipid Res 50: 303–132.
    1. Lin E, Armstrong-Moore D, Liang Z, Sweeney JF, Torres WE, et al. (2011) Contribution of adipose tissue to plasma 25-hydroxyvitamin D concentrations during weight loss following gastric bypass surgery. Obesity 19: 588–94.
    1. Lorente-Cebriàn S, Eriksson A, Dunlop T, Mejhert N, Dahlman I, et al. (2012) Differential effects of 1α,25-dihydroxycholecalciferol on MCP-1 and adiponectin production in human white adipocytes. Eur J Nutr 51: 335–342.
    1. Menendez C, Lage M, Peino R, Baldelli R, Concheiro P, et al. (2001) Retinoic acid and vitamin D(3) powerfully inhibit on vitro leptin secretion by human adipose tissue. J Endocrinol 170: 425–431.
    1. Tsuji K, Maeda T, Kawane T, Matsunuma A, Horiuchi N (2010) Leptin stimulates fibroblast growth factor 23 expression in bone and suppresses renal 1alpha,25-dihydroxyvitamin D3 synthesis in leptin-deficient mice. J Bone Miner Res 25: 1711–1723.
    1. Agarwal R, Hynson JE, Hecht TJ, Light RP, Sinha AD (2011) Short-term vitamin D receptor activation increases serum creatinine due to increased production with no effect on the glomerular filtration rate. Kidney Int 80: 1073–1079.
    1. Rosenvinge MM, Gedela K, Copas AJ, Wilkinson A, Sheehy CA, et al. (2010) Tenofovir-linked hyperparathyroidism is independently associated with the presence of vitamin D deficiency. J Acquir Immune Defic Syndr 54: 1127–1134.
    1. Signorello LB, Shi J, Cai Q, Zheng W, Williams SM, et al. (2011) Common variation in Vitamin D pathway genes predicts circulating 25-hydroxyvitamin D levels among African Americans. PLoS ONE 6(12): e28623 doi:
    1. Wright NC, Chen L, Niu J, Neogi T, Javiad K, et al. (2012) Defining physiologically « normal » vitamin D in African Americans. Osteoporos Int 23: 2283–2291.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner