Biological Trace Element Research

, Volume 171, Issue 1, pp 63–70 | Cite as

Serum Zinc Concentration and C-Reactive Protein in Individuals with Human Immunodeficiency Virus Infection: the Positive Living with HIV (POLH) Study

  • Krishna C. Poudel
  • Elizabeth R. Bertone-Johnson
  • Kalpana Poudel-Tandukar
Article

Abstract

Low zinc levels and chronic inflammation are common in individuals infected with human immunodeficiency virus (HIV). Zinc deficiency may promote systemic inflammation, but research on the role of zinc in inflammation among HIV-positive individuals taking account of anti-retroviral therapy is lacking. We assessed the association between serum zinc and C-reactive protein (CRP) concentration in a cohort of HIV-positive individuals. A cross-sectional survey was conducted among 311 HIV-positive individuals (177 men and 134 women) aged 18–60 years residing in Kathmandu, Nepal. High-sensitive or regular serum CRP concentrations were measured by the latex agglutination nephelometry or turbidimetric method, and zinc concentrations were measured by the atomic absorption method. Relationships were assessed using multiple linear regression analysis. The geometric means of zinc in men and women were 73.83 and 71.93 ug/dL, respectively, and of CRP were 1.64 and 0.96 mg/L, respectively. Mean serum CRP concentration was significantly decreased with increasing serum zinc concentration across zinc tertiles (P for trend = 0.010), with mean serum CRP concentration in the highest tertile of serum zinc concentration was 44.2 % lower than that in the lowest tertile. The mean serum CRP concentrations in men and women in the highest tertile of serum zinc concentrations were 30 and 35.9 % lower, respectively, than that in the lowest tertile (P for trend = 0.263 and 0.162, respectively). We found a significant inverse relation between log zinc and log CRP concentrations (beta for 1 unit change in log zinc; β = −1.79, p = 0.0003). Serum zinc concentration may be inversely associated with serum CRP concentration in HIV-positive individuals.

Keywords

Zinc Inflammation HIV infection C-reactive protein Nepal 

References

  1. 1.
    Deeks SG, Tracy R, Douek DC (2013) Systemic effects of inflammation on health during chronic HIV infection. Immunity 39:633–645CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G et al (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12:1365–1371CrossRefPubMedGoogle Scholar
  3. 3.
    Papagno L, Spina CA, Marchant A, Salio M, Rufer N et al (2004) Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLoS Biol 2:E20CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Smith MZ, Bastidas S, Karrer U, Oxenius A (2013) Impact of antigen specificity on CD4+ T cell activation in chronic HIV-1 infection. BMC Infect Dis 13:100CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Wittkop L, Bitard J, Lazaro E, Neau D, Bonnet F et al (2013) Effect of cytomegalovirus-induced immune response, self antigen-induced immune response, and microbial translocation on chronic immune activation in successfully treated HIV type 1-infected patients: the ANRS CO3 Aquitaine Cohort. J Infect Dis 207:622–627CrossRefPubMedGoogle Scholar
  6. 6.
    Feldman JG, Goldwasser P, Holman S, DeHovitz J, Minkoff H (2003) C-reactive protein is an independent predictor of mortality in women with HIV-1 infection. J Acquir Immune Defic Syndr 32:210–214CrossRefPubMedGoogle Scholar
  7. 7.
    Lau B, Sharrett AR, Kingsley LA, Post W, Palella FJ et al (2006) C-reactive protein is a marker for human immunodeficiency virus disease progression. Arch Intern Med 166:64–70CrossRefPubMedGoogle Scholar
  8. 8.
    Graham NM, Sorensen D, Odaka N, Brookmeyer R, Chan D et al (1991) Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS. J Acquir Immune Defic Syndr 4:976–980PubMedGoogle Scholar
  9. 9.
    Beach RS, Mantero-Atienza E, Shor-Posner G, Javier JJ, Szapocznik J et al (1992) Specific nutrient abnormalities in asymptomatic HIV-1 infection. AIDS 6:701–708CrossRefPubMedGoogle Scholar
  10. 10.
    Baum MK, Shor-Posner G, Lai S, Zhang G, Lai H et al (1997) High risk of HIV-related mortality is associated with selenium deficiency. J Acquir Immune Defic Syndr Hum Retrovirol 15:370–374CrossRefPubMedGoogle Scholar
  11. 11.
    Baum MK, Shor-Posner G, Zhang G, Lai H, Quesada JA et al (1997) HIV-1 infection in women is associated with severe nutritional deficiencies. J Acquir Immune Defic Syndr Hum Retrovirol 16:272–278CrossRefPubMedGoogle Scholar
  12. 12.
    Visser ME, Maartens G, Kossew G, Hussey GD (2003) Plasma vitamin A and zinc levels in HIV-infected adults in Cape Town, South Africa. Br J Nutr 89:475–482CrossRefPubMedGoogle Scholar
  13. 13.
    Campa A, Shor-Posner G, Indacochea F, Zhang G, Lai H et al (1999) Mortality risk in selenium-deficient HIV-positive children. J Acquir Immune Defic Syndr Hum Retrovirol 20:508–513CrossRefPubMedGoogle Scholar
  14. 14.
    Bunupuradah T, Ubolyam S, Hansudewechakul R, Kosalaraksa P, Ngampiyaskul C et al (2012) Correlation of selenium and zinc levels to antiretroviral treatment outcomes in Thai HIV-infected children without severe HIV symptoms. Eur J Clin Nutr 66:900–905CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Jones CY, Tang AM, Forrester JE, Huang J, Hendricks KM et al (2006) Micronutrient levels and HIV disease status in HIV-infected patients on highly active antiretroviral therapy in the Nutrition for Healthy Living cohort. J Acquir Immune Defic Syndr 43:475–482CrossRefPubMedGoogle Scholar
  16. 16.
    Papathakis PC, Rollins NC, Chantry CJ, Bennish ML, Brown KH (2007) Micronutrient status during lactation in HIV-infected and HIV-uninfected South African women during the first 6 mo after delivery. Am J Clin Nutr 85:182–192PubMedGoogle Scholar
  17. 17.
    Wellinghausen N, Kern WV, Jochle W, Kern P (2000) Zinc serum level in human immunodeficiency virus-infected patients in relation to immunological status. Biol Trace Elem Res 73:139–149CrossRefPubMedGoogle Scholar
  18. 18.
    Friis H, Sandstrom B (2002) Zinc and HIV infection. In: Friis H (ed) Micronutrients and HIV infection: CRC series in modern nutrition. CRC Press, Boca Raton, Florida, pp 159–181Google Scholar
  19. 19.
    Carcamo C, Hooton T, Weiss NS, Gilman R, Wener MH et al (2006) Randomized controlled trial of zinc supplementation for persistent diarrhea in adults with HIV-1 infection. J Acquir Immune Defic Syndr 43:197–201CrossRefPubMedGoogle Scholar
  20. 20.
    Koch J, Neal EA, Schlott MJ, Garcia-Shelton YL, Chan MF et al (1996) Zinc levels and infections in hospitalized patients with AIDS. Nutrition 12:515–518CrossRefPubMedGoogle Scholar
  21. 21.
    Koch J, Neal EA, Schlott MJ, Garcia-Shelton YL, Chan MF et al (1996) Serum zinc and protein levels: lack of a correlation in hospitalized patients with AIDS. Nutrition 12:511–514CrossRefPubMedGoogle Scholar
  22. 22.
    Edeas MA, Peltier E, Claise C, Khalfoun Y, Lindenbaum A (1996) Immunocytochemical study of uptake of exogenous carrier-free copper-zinc superoxide dismutase by peripheral blood lymphocytes. Cell Mol Biol (Noisy-le-grand) 42:1137–1143Google Scholar
  23. 23.
    Sprietsma JE (1997) Zinc-controlled Th1/Th2 switch significantly determines development of diseases. Med Hypotheses 49:1–14CrossRefPubMedGoogle Scholar
  24. 24.
    Cunningham-Rundles S, McNeeley DF, Moon A (2005) Mechanisms of nutrient modulation of the immune response. J Allergy Clin Immunol 115:1119–1128, quiz 1129CrossRefPubMedGoogle Scholar
  25. 25.
    Irlam JH, Visser MM, Rollins NN, Siegfried N (2010) Micronutrient supplementation in children and adults with HIV infection. Cochrane Database Syst Rev 12:CD003650Google Scholar
  26. 26.
    Baum MK, Campa A, Lai S, Lai H, Page JB (2003) Zinc status in human immunodeficiency virus type 1 infection and illicit drug use. Clin Infect Dis 37(Suppl 2):S117–S123CrossRefPubMedGoogle Scholar
  27. 27.
    Fufa H, Umeta M, Taffesse S, Mokhtar N, Aguenaou H (2009) Nutritional and immunological status and their associations among HIV-infected adults in Addis Ababa, Ethiopia. Food Nutr Bull 30:227–232CrossRefPubMedGoogle Scholar
  28. 28.
    Tang AM, Graham NM, Kirby AJ, McCall LD, Willett WC et al (1993) Dietary micronutrient intake and risk of progression to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type 1 (HIV-1)-infected homosexual men. Am J Epidemiol 138:937–951PubMedGoogle Scholar
  29. 29.
    Tang AM, Graham NM, Saah AJ (1996) Effects of micronutrient intake on survival in human immunodeficiency virus type 1 infection. Am J Epidemiol 143:1244–1256CrossRefPubMedGoogle Scholar
  30. 30.
    Tang AM, Graham NM, Chandra RK, Saah AJ (1997) Low serum vitamin B-12 concentrations are associated with faster human immunodeficiency virus type 1 (HIV-1) disease progression. J Nutr 127:345–351PubMedGoogle Scholar
  31. 31.
    Lai H, Lai S, Shor-Posner G, Ma F, Trapido E et al (2001) Plasma zinc, copper, copper:zinc ratio, and survival in a cohort of HIV-1-infected homosexual men. J Acquir Immune Defic Syndr 27:56–62CrossRefPubMedGoogle Scholar
  32. 32.
    Baum MK, Lai S, Sales S, Page JB, Campa A (2010) Randomized, controlled clinical trial of zinc supplementation to prevent immunological failure in HIV-infected adults. Clin Infect Dis 50:1653–1660CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Mocchegiani E, Muzzioli M, Gaetti R, Veccia S, Viticchi C et al (1999) Contribution of zinc to reduce CD4+ risk factor for ‘severe’ infection relapse in aging: parallelism with HIV. Int J Immunopharmacol 21:271–281CrossRefPubMedGoogle Scholar
  34. 34.
    Mocchegiani E, Veccia S, Ancarani F, Scalise G, Fabris N (1995) Benefit of oral zinc supplementation as an adjunct to zidovudine (AZT) therapy against opportunistic infections in AIDS. Int J Immunopharmacol 17:719–727CrossRefPubMedGoogle Scholar
  35. 35.
    Zeng L, Zhang L (2011) Efficacy and safety of zinc supplementation for adults, children and pregnant women with HIV infection: systematic review. Trop Med Int Health 16:1474–1482CrossRefPubMedGoogle Scholar
  36. 36.
    Bao B, Prasad AS, Beck FW, Fitzgerald JT, Snell D et al (2010) Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent. Am J Clin Nutr 91:1634–1641CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Beutler B (1995) TNF, immunity and inflammatory disease: lessons of the past decade. J Investig Med 43:227–235PubMedGoogle Scholar
  38. 38.
    Prasad AS, Bao B, Beck FW, Kucuk O, Sarkar FH (2004) Antioxidant effect of zinc in humans. Free Radic Biol Med 37:1182–1190CrossRefPubMedGoogle Scholar
  39. 39.
    Prasad AS, Beck FW, Bao B, Fitzgerald JT, Snell DC et al (2007) Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr 85:837–844PubMedGoogle Scholar
  40. 40.
    Shankar AH, Prasad AS (1998) Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr 68:447S–463SPubMedGoogle Scholar
  41. 41.
    Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C et al (1994) Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 344:1105–1110CrossRefPubMedGoogle Scholar
  42. 42.
    Pennington JE (1993) Therapy with antibody to tumor necrosis factor in sepsis. Clin Infect Dis 17(Suppl 2):S515–S519CrossRefPubMedGoogle Scholar
  43. 43.
    Opal SM, DePalo VA (2000) Anti-inflammatory cytokines. Chest 117:1162–1172CrossRefPubMedGoogle Scholar
  44. 44.
    Mburu AS, Thurnham DI, Mwaniki DL, Muniu EM, Alumasa FM (2010) The influence of inflammation on plasma zinc concentration in apparently healthy, HIV+ Kenyan adults and zinc responses after a multi-micronutrient supplement. Eur J Clin Nutr 64:510–517CrossRefPubMedGoogle Scholar
  45. 45.
    De Pablo-Bernal RS, Ruiz-Mateos E, Rosado I, Dominguez-Molina B, Alvarez-Rios AI et al (2014) TNF-alpha levels in HIV-infected patients after long-term suppressive cART persist as high as in elderly, HIV-uninfected subjects. J Antimicrob Chemother 69:3041–3046CrossRefPubMedGoogle Scholar
  46. 46.
    McKibben RA, Margolick JB, Grinspoon S, Li X, Palella FJ Jr et al (2014) Elevated levels of monocyte activation markers are associated with subclinical atherosclerosis in men with and those without HIV infection. J Infect Dis 211:1219–1228PubMedGoogle Scholar
  47. 47.
    Burdo TH, Lo J, Abbara S, Wei J, DeLelys ME et al (2011) Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV-infected patients. J Infect Dis 204:1227–1236CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Nordell AD, McKenna M, Borges AH, Duprez D, Neuhaus J et al (2014) Severity of cardiovascular disease outcomes among patients with HIV is related to markers of inflammation and coagulation. J Am Heart Assoc 3:e000844CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Borges AH, Weitz JI, Collins G, Baker JV, Levy Y et al (2014) Markers of inflammation and activation of coagulation are associated with anaemia in antiretroviral-treated HIV disease. AIDS 28:1791–1796CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Hileman CO, Labbato DE, Storer NJ, Tangpricha V, McComsey GA (2014) Is bone loss linked to chronic inflammation in antiretroviral-naive HIV-infected adults? A 48-week matched cohort study. AIDS 28:1759–1767CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Tien PC, Choi AI, Zolopa AR, Benson C, Tracy R et al (2010) Inflammation and mortality in HIV-infected adults: analysis of the FRAM study cohort. J Acquir Immune Defic Syndr 55:316–322CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Tenorio AR, Zheng Y, Bosch RJ, Krishnan S, Rodriguez B et al (2014) Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment. J Infect Dis 210:1248–1259CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    NCASC (2012) Nepal Country Progress Report 2012: to contribute to Global AIDS Response Progress Report 2012. National Centre for AIDS and STD Control, KathmanduGoogle Scholar
  54. 54.
    NCASC (2007) National estimates of HIV infections, Nepal. National Centre for AIDS and STD Control, KathmanduGoogle Scholar
  55. 55.
    Amiya RM, Poudel KC, Poudel-Tandukar K, Kobayashi J, Pandey BD et al (2011) Physicians are a key to encouraging cessation of smoking among people living with HIV/AIDS: a cross-sectional study in the Kathmandu Valley, Nepal. BMC Public Health 11:677CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Poudel KC, Palmer PH, Jimba M, Mizoue T, Kobayashi J et al (2014) Coinfection with hepatitis C virus among HIV-positive people in the Kathmandu Valley, Nepal. J Int Assoc Provid AIDS Care 13:277–283CrossRefPubMedGoogle Scholar
  57. 57.
    Poudel-Tandukar K, Poudel KC, Jimba M, Kobayashi J, Johnson CA et al (2013) Serum 25-hydroxyvitamin D levels and C-reactive protein in persons with human immunodeficiency virus infection. AIDS Res Hum Retroviruses 29:528–534CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Poudel-Tandukar K, Bertone-Johnson ER, Palmer PH, Poudel KC (2014) C-reactive protein and depression in persons with human immunodeficiency virus infection: the Positive Living with HIV (POLH) Study. Brain, Behavior, and Immunity 42:89–95Google Scholar
  59. 59.
    Poudel KC, Buchanan DR, Poudel-Tandukar K (2015) Effects of a community-based HIV risk reduction intervention among HIV-positive individuals: results of a quasi-experimental study in Nepal. AIDS Educ Prev 27:240–256CrossRefPubMedGoogle Scholar
  60. 60.
    Poudel KC, Okumura J, Sherchand JB, Jimba M, Murakami I et al (2003) Mumbai disease in far western Nepal: HIV infection and syphilis among male migrant-returnees and non-migrants. Trop Med Int Health 8:933–939CrossRefPubMedGoogle Scholar
  61. 61.
    Poudel KC, Poudel-Tandukar K, Yasuoka J, Joshi AB, Jimba M (2010) Correlates of sharing injection equipment among male injecting drug users in Kathmandu, Nepal. Int J Drug Policy 21:507–510CrossRefPubMedGoogle Scholar
  62. 62.
    Poudel KC, Nakahara S, Poudel-Tandukar K, Yasuoka J, Jimba M (2009) Unsafe sexual behaviors among HIV-positive men in Kathmandu Valley, Nepal. AIDS Behav 13:1143–1150CrossRefPubMedGoogle Scholar
  63. 63.
    Poudel KC, Poudel-Tandukar K, Nakahara S, Yasuoka J, Jimba M (2011) Knowing the consequences of unprotected sex with seroconcordant partner is associated with increased safer sex intentions among HIV-positive men in Kathmandu, Nepal. J Health Popul Nutr 29:191–199CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Wfood2 (1996) World Food 2 Computer Software Package. Version 1.0. The Regents of the University of California, Berkeley, CAGoogle Scholar
  65. 65.
    Prasad AS, Beck FW, Grabowski SM, Kaplan J, Mathog RH (1997) Zinc deficiency: changes in cytokine production and T-cell subpopulations in patients with head and neck cancer and in noncancer subjects. Proc Assoc Am Physicians 109:68–77PubMedGoogle Scholar
  66. 66.
    Hennig B, Toborek M, McClain CJ (1996) Antiatherogenic properties of zinc: implications in endothelial cell metabolism. Nutrition 12:711–717CrossRefPubMedGoogle Scholar
  67. 67.
    Ho E, Courtemanche C, Ames BN (2003) Zinc deficiency induces oxidative DNA damage and increases p53 expression in human lung fibroblasts. J Nutr 133:2543–2548PubMedGoogle Scholar
  68. 68.
    Jaattela M, Mouritzen H, Elling F, Bastholm L (1996) A20 zinc finger protein inhibits TNF and IL-1 signaling. J Immunol 156:1166–1173PubMedGoogle Scholar
  69. 69.
    Reiterer G, Toborek M, Hennig B (2004) Peroxisome proliferator activated receptors alpha and gamma require zinc for their anti-inflammatory properties in porcine vascular endothelial cells. J Nutr 134:1711–1715PubMedGoogle Scholar
  70. 70.
    Singh A, Deuster PA, Moser PB (1990) Zinc and copper status in women by physical activity and menstrual status. J Sports Med Phys Fitness 30:29–36PubMedGoogle Scholar
  71. 71.
    Lukaski HC, Hoverson BS, Gallagher SK, Bolonchuk WW (1990) Physical training and copper, iron, and zinc status of swimmers. Am J Clin Nutr 51:1093–1099PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Krishna C. Poudel
    • 1
  • Elizabeth R. Bertone-Johnson
    • 2
  • Kalpana Poudel-Tandukar
    • 3
  1. 1.Department of Health Promotion and Policy, School of Public Health and Health SciencesUniversity of Massachusetts AmherstAmherstUSA
  2. 2.Department of Biostatistics and Epidemiology, School of Public Health and Health SciencesUniversity of Massachusetts AmherstAmherstUSA
  3. 3.College of NursingUniversity of Massachusetts AmherstAmherstUSA

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