Examining Associations of HIV and Iron Status with Nutritional and Inflammatory Status, Anemia, and Dietary Intake in South African Schoolchildren

Charlene Goosen, Jeannine Baumgartner, Nadja Mikulic, Shaun L Barnabas, Mark F Cotton, Michael B Zimmermann, Renée Blaauw, Charlene Goosen, Jeannine Baumgartner, Nadja Mikulic, Shaun L Barnabas, Mark F Cotton, Michael B Zimmermann, Renée Blaauw

Abstract

The etiology of multifactorial morbidities such as undernutrition and anemia in children living with the human immunodeficiency virus (HIV) (HIV+) on antiretroviral therapy (ART) is poorly understood. Our objective was to examine associations of HIV and iron status with nutritional and inflammatory status, anemia, and dietary intake in school-aged South African children. Using a two-way factorial case-control design, we compared four groups of 8 to 13-year-old South African schoolchildren: (1) HIV+ and low iron stores (inflammation-unadjusted serum ferritin ≤ 40 µg/L), n = 43; (2) HIV+ and iron sufficient non-anemic (inflammation-unadjusted serum ferritin > 40 µg/L, hemoglobin ≥ 115 g/L), n = 41; (3) children without HIV (HIV-ve) and low iron stores, n = 45; and (4) HIV-ve and iron sufficient non-anemic, n = 45. We assessed height, weight, plasma ferritin (PF), soluble transferrin receptor (sTfR), plasma retinol-binding protein, plasma zinc, C-reactive protein (CRP), α-1-acid glycoprotein (AGP), hemoglobin, mean corpuscular volume, and selected nutrient intakes. Both HIV and low iron stores were associated with lower height-for-age Z-scores (HAZ, p < 0.001 and p = 0.02, respectively), while both HIV and sufficient iron stores were associated with significantly higher CRP and AGP concentrations. HIV+ children with low iron stores had significantly lower HAZ, significantly higher sTfR concentrations, and significantly higher prevalence of subclinical inflammation (CRP 0.05 to 4.99 mg/L) (54%) than both HIV-ve groups. HIV was associated with 2.5-fold higher odds of iron deficient erythropoiesis (sTfR > 8.3 mg/L) (95% CI: 1.03-5.8, p = 0.04), 2.7-fold higher odds of subclinical inflammation (95% CI: 1.4-5.3, p = 0.004), and 12-fold higher odds of macrocytosis (95% CI: 6-27, p < 0.001). Compared to HIV-ve counterparts, HIV+ children reported significantly lower daily intake of animal protein, muscle protein, heme iron, calcium, riboflavin, and vitamin B12, and significantly higher proportions of HIV+ children did not meet vitamin A and fiber requirements. Compared to iron sufficient non-anemic counterparts, children with low iron stores reported significantly higher daily intake of plant protein, lower daily intake of vitamin A, and lower proportions of inadequate fiber intake. Along with best treatment practices for HIV, optimizing dietary intake in HIV+ children could improve nutritional status and anemia in this vulnerable population. This study was registered at clinicaltrials.gov as NCT03572010.

Keywords: HIV; South Africa; anemia; children; dietary intake; iron deficiency; nutritional status; stunting.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

References

    1. Joint United Nations Programme on HIV/AIDS (UNAIDS) UNAIDS Data. [(accessed on 26 January 2021)];2019 Available online: .
    1. World Health Organization Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection. [(accessed on 26 January 2021)];2016 Available online:
    1. South African National Department of Health National Consolidated Guidelines for the Prevention of Mother-to-Child Transmission of HIV (PMTCT), and the Management of HIV in Children, Adolescents and Adults. [(accessed on 26 January 2021)];2015 Available online: .
    1. Violari A., Cotton M.F., Gibb D.M., Babiker A.G., Steyn J., Madhi S.A., Jean-Philippe P., McIntyre J.A. Early antiretroviral therapy and mortality among HIV-infected infants. N. Engl. J. Med. 2008;359:2233–2244. doi: 10.1056/NEJMoa0800971.
    1. Iyun V., Technau K.-G., Eley B., Rabie H., Boulle A., Fatti G., Egger M., Tanser F., Wood R., Fairlie L., et al. Earlier antiretroviral therapy initiation and decreasing mortality among HIV-infected infants initiating antiretroviral therapy within 3 months of age in South Africa, 2006–2017. Pediatr. Infect. Dis. J. 2020;39:127–133. doi: 10.1097/INF.0000000000002516.
    1. Lowenthal E.D., Bakeera-Kitaka S., Marukutira T., Chapman J., Goldrath K., Ferrand R.A. Perinatally acquired HIV infection in adolescents from sub-Saharan Africa: A review of emerging challenges. Lancet Infect. Dis. 2014;14:627–639. doi: 10.1016/S1473-3099(13)70363-3.
    1. Klatt N.R., Funderburg N.T., Brenchley J.M. Microbial translocation, immune activation, and HIV disease. Trends Microbiol. 2013;21:6–13. doi: 10.1016/j.tim.2012.09.001.
    1. Labadarios D., Steyn N.P., Maunder E., MacIntyre U., Gericke G., Swart R., Huskisson J., Dannhauser A., Vorster H.H., Nesmvuni A.E., et al. The National Food Consumption Survey (NFCS): South Africa, 1999. Public Health Nutr. 2005;8:533–543. doi: 10.1079/PHN2005816.
    1. South African National Department of Health. South African Medical Research Council OrcMacro South Africa Demographic and Health Survey 2003. [(accessed on 26 January 2021)];2007 Available online: .
    1. Labadarios D., Swart R., Maunder E.M.W., Kruger H.S., Gericke G.J., Kuzwayo P.M.N., Ntsie P.R., Steyn N.P., Schloss I., Dhansay M.A., et al. Executive summary of the National Food Consumption Survey Fortification Baseline (NFCS-FB-I) South Africa, 2005. S. Afr. J. Clin. Nutr. 2008;21:245–300.
    1. Shisana O., Labadarios D., Rehle T., Simbayi L., Zuma K., Dhansay A., Reddy P., Parker W., Hoosain E., Naidoo P., et al. The South African National Health and Nutrition Examination Survey, 2012 (SANHANES-1) [(accessed on 26 January 2021)];2014 Available online: .
    1. South African National Department of Health. Statistics South Africa. South African Medical Research Council and ICF 2019. South Africa Demographic and Health Survey. 2016. [(accessed on 26 January 2021)]; Available online: .
    1. United Nations Children’s Fund Strategy for improved nutrition of children and women in developing countries. Indian J. Pediatr. 1990;58:13–24. doi: 10.1007/BF02810402.
    1. Anabwani G., Navario P. Nutrition and HIV/AIDS in sub-Saharan Africa: An overview. Nutrition. 2005;21:96–99. doi: 10.1016/j.nut.2004.09.013.
    1. FAO. IFAD. UNICEF. WFP. WHO The State of Food Security and Nutrition in the World 2020. Transforming Food Systems for Affordable Healthy Diets. [(accessed on 26 January 2021)];2020 Available online: .
    1. Chaparro C.M., Suchdev P.S. Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries. Ann. N. Y. Acad. Sci. 2019;1450:15–31. doi: 10.1111/nyas.14092.
    1. Kassebaum N.J. The global burden of anemia. Hematol. Oncol. Clin. N. Am. 2016;30:247–308. doi: 10.1016/j.hoc.2015.11.002.
    1. Ezeamama A.E., Sikorskii A., Bajwa R.K., Tuke R., Kyeyune R.B., Fenton J.I., Guwatudde D., Fawzi W.W. Evolution of anemia types during antiretroviral therapy-implications for treatment outcomes and quality of life among HIV-infected adults. Nutrients. 2019;11:755. doi: 10.3390/nu11040755.
    1. Redig A.J., Berliner N. Pathogenesis and clinical implications of HIV-related anemia in 2013. Hematol. Am. Soc. Hematol. Educ. Progr. 2013;2013:377–381. doi: 10.1182/asheducation-2013.1.377.
    1. Ganz T. Anemia of inflammation. N. Engl. J. Med. 2019;381:1148–1157. doi: 10.1056/NEJMra1804281.
    1. Calis J.C.J., van Hensbroek M.B., De Haan R.J., Moons P., Brabin B.J., Bates I. HIV-associated anemia in children: A systematic review from a global perspective. AIDS. 2008;22:1099–1112. doi: 10.1097/QAD.0b013e3282fa759f.
    1. Kufel W.D., Hale C.M., Sidman E.F., Orellana C.E., Miller C.D. Nucleoside Reverse Transcriptase Inhibitor (NRTI) associated macrocytosis. Int. J. Virol. AIDS. 2016;3:18. doi: 10.23937/2469-567X/1510018.
    1. Abioye A.I., Andersen C.T., Sudfeld C.R., Fawzi W.W. Anemia, iron status, and HIV: A systematic review of the evidence. Adv. Nutr. 2020;11:1334–1363. doi: 10.1093/advances/nmaa037.
    1. World Health Organization WHO Guideline on Use of Ferritin Concentrations to Assess Iron Status in Individuals and Populations. [(accessed on 26 January 2021)];2020 Available online: .
    1. De Onis M., Onyango A.W., Borghi E., Siyam A., Nishida C., Siekmann J. Development of a WHO growth reference for school-aged children and adolescents. Bull. World Health Organ. 2007;85:660–667. doi: 10.2471/BLT.07.043497.
    1. World Health Organization Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity. [(accessed on 26 January 2021)];2011 Available online:
    1. World Health Organization Training Course on Child Growth Assessment. [(accessed on 26 January 2021)];2008 Available online:
    1. Erhardt J.G., Estes J.E., Pfeiffer C.M., Biesalski H.K., Craft N.E. Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique. J. Nutr. 2004;134:3127–3132. doi: 10.1093/jn/134.11.3127.
    1. Brnić M., Wegmüller R., Zeder C., Senti G., Hurrell R.F. Influence of phytase, EDTA, and polyphenols on zinc absorption in adults from porridges fortified with zinc sulfate or zinc oxide. J. Nutr. 2014;144:1467–1473. doi: 10.3945/jn.113.185322.
    1. Goosen C., Blaauw R. The development of a quantified food frequency questionnaire for assessing iron nutrition in schoolchildren from resource-limited settings in Cape Town, South Africa. Ecol. Food Nutr. 2021 doi: 10.1080/03670244.2021.1881896.
    1. South African Food Data System (SAFOODS) SAMRC Food Quantities Manual for South Africa. 3rd ed. SAMRC; Cape Town, South Africa: 2018.
    1. South African Food Data System (SAFOODS) SAMRC Food Composition Tables for South Africa. 5th ed. SAMRC; Cape Town, South Africa: 2017.
    1. Harris P.A., Taylor R., Minor B.L., Elliott V., Fernandez M., O’Neal L., McLeod L., Delacqua G., Delacqua F., Kirby J., et al. The REDCap consortium: Building an international community of software platform partners. J. Biomed. Inform. 2019;95:103208. doi: 10.1016/j.jbi.2019.103208.
    1. Harris P.A., Taylor R., Thielke R., Payne J., Gonzalez N., Conde J.G. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J. Biomed. Inform. 2009;42:377–381. doi: 10.1016/j.jbi.2008.08.010.
    1. Namaste S.M.L., Ou J., Williams A.M., Young M.F., Yu E.X., Suchdev P.S. Adjusting iron and vitamin A status in settings of inflammation: A sensitivity analysis of the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) approach. Am. J. Clin. Nutr. 2020;112:458S–467S. doi: 10.1093/ajcn/nqaa141.
    1. McDonald C.M., Suchdev P.S., Krebs N.F., Hess S.Y., Wessells K.R., Ismaily S., Rahman S., Wieringa F.T., Williams A.M., Brown K.H., et al. Adjusting plasma or serum zinc concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am. J. Clin. Nutr. 2020;111:927–937. doi: 10.1093/ajcn/nqz304.
    1. De Pee S., Dary O. Biochemical indicators of vitamin A deficiency: Serum retinol and serum retinol binding protein. J. Nutr. 2002;132:2895S–2901S. doi: 10.1093/jn/132.9.2895S.
    1. International Zinc Nutrition Consultative Group (IZINCG) Assessing Population Zinc Status with Serum Zinc Concentration. [(accessed on 26 January 2021)];2012 Available online: .
    1. South African Food Data System (SAFOODS) Food Composition Database, Version 2019. SAMRC; Cape Town, South Africa: 2019.
    1. Institute of Medicine Dietary Reference Intakes. [(accessed on 26 January 2021)];2006 Available online: .
    1. Institute of Medicine Dietary Reference Intakes for Calcium and Vitamin D. [(accessed on 26 January 2021)];2011 Available online: .
    1. Shet A., Bhavani P.K., Kumarasamy N., Arumugam K., Poongulali S., Elumalai S., Swaminathan S. Anemia, diet and therapeutic iron among children living with HIV: A prospective cohort study. BMC Pediatr. 2015;15 doi: 10.1186/s12887-015-0484-7.
    1. Feucht U.D., Van Bruwaene L., Becker P.J., Kruger M. Growth in HIV-infected children on long-term antiretroviral therapy. Trop. Med. Int. Health. 2016;21:619–629. doi: 10.1111/tmi.12685.
    1. Bobat R., Coovadia H., Moodley D., Coutsoudis A., Gouws E. Growth in early childhood in a cohort of children born to HIV-1-infected women from Durban, South Africa. Ann. Trop. Paediatr. 2001;21:203–210. doi: 10.1080/02724930120077772.
    1. Venkatesh K.K., Lurie M.N., Triche E.W., De Bruyn G., Harwell J.I., McGarvey S.T., Gray G.E. Growth of infants born to HIV-infected women in South Africa according to maternal and infant characteristics. Trop. Med. Int. Health. 2010;15:1364–1374. doi: 10.1111/j.1365-3156.2010.02634.x.
    1. World Health Organization Report of the WHO Technical Reference Group, Paediatric HIV/ART Care Guideline Group Meeting. [(accessed on 26 January 2021)]; Available online: .
    1. Burton R., Giddy J., Stinson K. Prevention of mother-to-child transmission in South Africa: An ever-changing landscape. Obstet. Med. 2015;8:5–12. doi: 10.1177/1753495X15570994.
    1. Armitage A.E., Moretti D. The importance of iron status for young children in low- and middle-income countries: A narrative review. Pharmaceuticals. 2019;12:59. doi: 10.3390/ph12020059.
    1. Drakesmith H., Prentice A.M. Hepcidin and the iron-infection axis. Science. 2012;338:768–772. doi: 10.1126/science.1224577.
    1. Hurrell R., Egli I. Iron bioavailability and dietary reference values. Am. J. Clin. Nutr. 2010;91:1461S–1467S. doi: 10.3945/ajcn.2010.28674F.
    1. Labadarios D., Steyn N., Mgijima C., Daldla N. Review of the South African nutrition policy 1994–2002 and targets for 2007: Achievements and challenges. Nutrition. 2005;21:100–108. doi: 10.1016/j.nut.2004.09.014.
    1. Musakwa N., Feeley A., Magwete M., Patz S., McNamara L., Sanne I., Long L., Evans D. Dietary intake among paediatric HIV-positive patients initiating antiretroviral therapy in Johannesburg, South Africa. Vulnerable Child. Youth Stud. 2020;15:155–170. doi: 10.1080/17450128.2019.1668581.
    1. Shiau S., Webber A., Strehlau R., Patel F., Coovadia A., Kozakowski S., Brodlie S., Yin M.T., Kuhn L., Arpadi S.M. Dietary inadequacies in HIV-infected and uninfected school-aged children in Johannesburg, South Africa. J. Pediatr. Gastroenterol. Nutr. 2017;65:332–337. doi: 10.1097/MPG.0000000000001577.
    1. Beck K.L., Conlon C.A., Kruger R., Coad J. Dietary determinants of and possible solutions to iron deficiency for young women living in industrialized countries: A review. Nutrients. 2014;6:3747–3776. doi: 10.3390/nu6093747.
    1. Kruger H.S., Balk L.J., Viljoen M., Meyers T.M. Positive association between dietary iron intake and iron status in HIV-infected children in Johannesburg, South Africa. Nutr. Res. 2013;33:50–58. doi: 10.1016/j.nutres.2012.11.008.
    1. Gibson R., Hotz C., Temple L., Yeudall F., Mtitimuni B., Ferguson E. Dietary strategies to combat deficiencies of iron, zinc and vitamin A in developing countries: Development, implementation, monitoring and evaluation. Food Nutr. Bull. 2000;21:219–231. doi: 10.1177/156482650002100218.
    1. McPherson R.S., Hoelscher D.M., Alexander M., Scanlon K.S., Serdula M.K. Dietary assessment methods among school-aged children: Validity and reliability. Prev. Med. 2000;31:S11–S33. doi: 10.1006/pmed.2000.0631.
    1. Gibson R., editor. Principles of Nutritional Assessment. Oxford University Press; New York, NY, USA: 2005. Chapter 3: Measuring food consumption of individuals; pp. 41–64.
    1. World Health Organization Nutrient Requirements for People Living with HIV/AIDS: Report of a Technical Consultation. [(accessed on 26 January 2021)];2003 Available online: .
    1. Zimmermann M.B., Hurrell R.F. Nutritional iron deficiency. Lancet. 2007;370:511–520. doi: 10.1016/S0140-6736(07)61235-5.

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