Assessment of Some Micronutrients and Vitamins of HIV Positive Patients in South-South Nigeria

Omolumen LE¹, Iweka FK¹, Iyevhobu KO^2,3*, Asibor E⁴, Usiobeigbe OS¹, Obohwemu KO⁵, Okparaku SO², Akindele IA⁶, Bisiriyu AH⁷, Irobonosen IO⁸, Oikerhe EG⁹, Ikede RE¹⁰, Animasaun OS¹¹, Ogundana FN¹², Ng’Andwe K⁵, Lagundoye SB¹³, Astaharam AJ¹⁴, Omoaka MQ¹

¹Department of Chemical Pathology, Faculty of Medical Laboratory Science, Ambrose Alli University, Ekpoma, Edo State, Nigeria
²Department of Medical Microbiology, Faculty of Medical Laboratory Science, Ambrose Alli University, Ekpoma, Edo State, Nigeria
³St Kenny Research Consult, Ekpoma, Edo State, Nigeria
⁴Department of Histopathology and Cytopathology, Faculty of Medical Laboratory Science, Ambrose Alli University, Ekpoma, Edo State, Nigeria
⁵Department of Health, Wellbeing and Social Care, Global Banking School, Birmingham, United Kingdom
⁶Department of Medical Microbiology, Lead City University, Ibadan, Oyo State, Nigeria
⁷Nigeria Field Epidemiology and Laboratory Training Program (NFELTP), Nigeria
⁸Department of Haematology and Blood Transfusion Science, Faculty of Medical Laboratory Science, Ambrose Alli University, Ekpoma, Edo State, Nigeria
⁹Nigeria Field Epidemiology and Laboratory Training Programme (NFELTP), Abuja, Nigeria
¹⁰Department of Medical Laboratory Science, Federal Medical Centre, Owo, Ondo State, Nigeria
¹¹Department of Medical Laboratory Services (Chemical Pathology), Igbinedion University Teaching Hospital, Okada, Edo State, Nigeria
¹²Department of Chemical Pathology, Faculty of Health Sciences, College of Health Sciences, Igbinedion University, Okada, Edo State, Nigeria
¹³Department of Medical Laboratory Science, Igbinedion University, Okada, Edo State, Nigeria
¹⁴National Ear Care Centre, Kaduna, Kaduna State, Nigeria

*Correspondence author: Iyevhobu Kenneth Oshiokhayamhe, Department of Medical Microbiology, Faculty of Medical Laboratory Science, Ambrose Alli University, Ekpoma, Edo State, Nigeria and St Kenny Research Consult, Ekpoma, Edo State, Nigeria; Email: [email protected]

Copyright^© 2024 by Omolumen LE, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation: Omolumen LE, et al. Assessment of Some Micronutrients and Vitamins of HIV Positive Patients in South-South Nigeria. Jour Clin Med Res. 2024;5(3):1-12.

Table 1: Demographic characteristics of the study subjects.

Table 2: Calcium, zinc, copper, iron, vitamin D and B12 levels of HIV positive subjects and control.

Table 3: Calcium, Zinc, Copper, Iron, Vitamins D and B12 levels of HIV positive Subjects with respect to gender.

Table 4: Calcium, Zinc, Copper, Iron, Vitamins D and B12 levels of HIV positive Subjects with respect to age.

Table 5: Calcium, Zinc, Copper, Iron, Vitamins D and B12 levels of HIV positive Subjects with respect to treatment duration.

Table 6: Pearson Correlation of Calcium, Zinc, Copper, Iron, Vitamin D and B12 levels of HIV positive subjects.

Discussion

Human Immunodeficiency Virus (HIV) infection continues to be a serious health issue in most parts of the world, with a global prevalence of 0.7% among adults, the majority being in developing countries with limited healthcare resources.  Nowadays, micronutrients have become a part of the immunotherapeutic approach against cancer, inflammatory diseases, autoimmune diseases, etc [19,20]. In recent years, the importance of nutrition in human health has received growing attention. Therapeutic and preventive supplementation with vitamins and micronutrients has been used successfully for a long time for many clinical conditions [21,22]. The aim of this study is to assess the total Iron, Vitamin D, Vitamin B12 and some micro nutrients (copper, zinc and calcium) levels in HIV positive subjects in Central Hospital, Benin City, Edo State.

In this study vitamin B12 was significantly lower in HIV positive subjects compared normal healthy control (p<0.05). Multiple factors are responsible for the low levels of serum vitamin B12 in HIV positive patients, like chronic diarrhea leading to malabsorption, gastric mucosal damage by HIV and opportunistic infections and intrinsic factor due to injury of the gastric mucosa [23]. During the early stages of HIV infection, due to increased lymphocyte turnover, fast dividing immune cells cause increased consumption of micronutrients contributing towards one of the etiologies of vitamin B12 deficiency in HIV patients [20-25]. Deficiency of vitamin B12 contributes to disorders in methylation affecting the immune function and NK Cell activity [26]. It increases the number of cytotoxic T cells and also participates in antibody synthesis. Low serum vitamin B12 levels affect the composition of intestinal microbiota in the gastrointestinal tract altering the gut barrier defense mechanism. A recent study has also revealed that vitamin B12 is a cofactor of transcriptional regulators and anti-repressors [27]. The finding of this study is in agreement with previous studies which reported significant decrease in vitamin B12 of HIV positive subjects in comparison with normal healthy control [28-30].

In this study vitamin D was significantly lower in HIV positive subjects compared normal healthy control (p<0.05). Well-known risk factors impairing bone maintenance and attributing to low levels of vitamin D in HIV infection include minimized exposure to sunlight and nutritive intake, insufficient absorption, fatty liver and renal damage encouraged anomalous vitamin D activation, altered bioavailability of non-hydroxylated vitamin D in adipose tissue and the antiretroviral treatment intervening vitamin D metabolism [29,30]. Since the virus itself may induce hypovitaminosis D through many mechanisms (increased levels of TNF-α, inhibition of renal hydroxylation and induction of 25-hydroxyvitamin D consumption by the macrophages and lymphocytes), the abnormal biochemical features found in our HIV-infected subjects compared with the controls, in particular the lower vitamin D levels, may support the hypothesis that HIV per se might play a role in the pathogenesis of bone loss [31].

Vitamin D was significantly lower (p<0.05) in age group 41 years and above in comparison with age group 20 – 40 years (p>0.05). This finding is consistent with prior findings in HIV carriers [22-25]. Allavena, et al., and Okparaku, et al., observe substantial correlation between age and vitamin D, one of the justifications may comprise the samples from younger HIV cohorts with few patients over 60 years of age, identical to the current research, which consisted majority of patients ranging within 23-47 years of age [32,33]. The current work revealed non-significant difference vitamin D among HIV positive subjects with respect to gender which is consistent with other studies conducted on HIV infected individuals [32-36].

Hypovitaminosis D is a risk factor for developing comorbidities including infectious diseases as well as immune disorders in patients infected with HIV [33]. Studies have shown that though ART is associated with a decreased prevalence of opportunistic gastrointestinal diseases and incidence of malnutrition, gastrointestinal infections and severe gastroenteritis, which alter micronutrient absorption, may persist after ART initiation [24]. Several HIV medications, particularly nucleoside reverse transcriptase inhibitors, can inhibit the replication of mitochondrial DNA and cause vomiting and diarrhea that can reduce the absorption or increase the losses of several micronutrients [35,36].

Calcium was significantly lower in HIV positive subjects compared with healthy control (p<0.05). Studies have shown that some minerals/trace elements may be key factors in maintaining health despite human immunodeficiency virus infection and in reducing mortality [34].Each of the mineral/trace elements examined in this study may contribute to the general well-being of HIV-infected persons. Calcium has been shown to reduce diarrhoea in HIV-positive/AIDS patients (Tang et al., 2016). Therefore, the results obtained from this study tend to suggest that patients with a high dietary intake might be able to replace lost calcium and in turn reduce the burden of diarrhoea. This finding is in agreement with previous studies which reported significant decrease in calcium among HIV positive subjects compared with healthy control [37-39].

Iron was significantly lower in HIV positive subjects compared with healthy control (p<0.05). Iron is one of the micronutrients that is commonly deficient in HIV infection [11]. Iron is essential for the formation and functioning of red blood cells and vitamin C is known to promote the absorption of iron [15]. In male patients, the iron intake was higher than in female subjects. The reason for this discrepancy is not clear, but it may be related to the fact that iron is lacking in women’s food due to a lack of knowledge, consuming foods/diets deficient in iron or because of extra demands during the menstrual cycle (women need extra iron until they pass the menopause stage) [38-40]. This finding is in agreement with previous studies which reported significant decrease in iron among HIV positive subjects compared with healthy control [24-27].

The present study demonstrated that HIV-infected subjects had significantly lower zinc concentration when compared with the control subjects. This observation is in agreement with previous reports [29-33]. This finding may be attributed to high demand in zinc because HIV nucleocapsid and integrase proteins that are essential for assembly of infectious virions contain zinc fingers that require zinc for normal structure and functioning [5]. Zinc deficiency is associated with impaired immune function and an increased susceptibility to infection. Zinc deficiency may result due to malnutrition [30]. One of the factors responsible for malnutrition in an HIV-infected person is reduced appetite, which could be due to difficulty in ingesting food as a result of infections such as oral thrush or oesophagitis caused by Candida, a common opportunistic infection in HIV-infected people and fever, side effects of medicines or depression. Poor absorption of nutrients may be due to accompanying diarrhea which may be because of bacterial infections such as Salmonella or Mycobacterium avium intercellular; viral such as CMV or parasitic infections such as Giardia, Cryptosporidium parvum and Enterocytozoon bieneusi; due to nausea/vomiting as a side effect of medications used to treat HIV or opportunistic infections [7].

The serum zinc level of the HIV-infected subjects on ART for more than one year and did not show any significant difference compared with HIV positive subjects on ART for less than one year. This finding is in consonance with previous report [31-34]. The ART treatment and its duration seem to have no effect on zinc level. Deficiencies of these micronutrients may result in fatigue, depression and widespread abnormalities in connective tissue, such as inflamed gingivae, petechiae, perifollicular hemorrhages and impaired wound healing, coiled hairs, hyperkeratosis and bleeding into body cavities [35-37]. Furthermore, the association between serum zinc level with respect to age and gender was not statistically significant (p>0.05). This shows that gender and age may not be predictor/risk factor of zinc deficiency among HIV positive subjects. This observation is in agreement with previous reports [10,15,18].

Serum copper in this study was significantly lower in HIV-positive subjects compared with HIV sero-negative subjects. This finding is agreement with another study in Ethiopia [2]. However, this observation is in contrast with previous reports that found significantly higher serum copper in HIV-seropositive subjects than in controls but considerably lower than in pre-HAART levels [1,13,16,17]. Lawal, et al., and Nwegbu, et al., both reported a significant increase in the mean plasma copper concentration of HIV-infected subjects when compared with the control group. The mean serum copper level of HIV-infected subjects on ART for less than one year was non-significantly lower than HIV-positive patients on drugs for over one year. Copper is required for immune complex formation, blood and coagulation factors formation. It is a major micronutrient required by the body in HIV infection [14,17]. Copper has been established as an acute phase reactant and its serum level has been shown to change significantly in a range of acute and chronic infective, inflammatory and neoplastic processes owing to increased reproductive of ceruloplasmin [4]. Serum copper has been shown to return to normality after overcoming the initial acute phase of the associated disease [18].

In general, there was significantly lower vitamins and micronutrients among HIV-positive subjects compared with healthy control. This is probably due to their high consumption of carbohydrate sources like maize meal, which contains only low levels of these nutrients [28. The results in this study are consistent with findings by Onyango, et al., that there was a lower intake of energy as well as most of the other nutrients among HIV seropositive patients. Energy intake is related to the stage of the infection, rapid weight loss, anorexia, opportunistic infections, malabsorption and altered metabolism [8]. Thus, it is clear that HIV-infected patients are at increased nutritional risk. Energy requirements increase significantly as the HIV disease progresses [42-54]. This may thus be viewed as a bad trend for patients with low energy intake as reported in this study. The higher energy intake assists to a certain degree in reducing wasting and improves the well-being of the patients [43].

Conclusion

In conclusion, calcium, zinc, copper, Iron, Vitamin B12 and Vitamin D were significantly lower in HIV positive subjects compared with healthy control (p<0.05). Calcium, zinc, copper, Iron, Vitamins B12 and D were non-significantly higher in male HIV positive subjects in comparison with female subjects (p>0.05). Calcium, Iron, Vitamins B12 and D were significantly lower (p<0.05) in age group 41 years and above in comparison with age group 20 – 40 years, while Zinc and Copper were non-significant (p>0.05). Calcium, Iron, Vitamins B12 and D were significantly higher in HIV positive subjects undergoing treatment for over a year compared with those undergoing treatment for less than one year. Calcium, Iron, Vitamins B12 and D were significantly lower (p<0.05) in age group 41 years and above in comparison with age group 20 – 40 years, while Zinc and Copper were non-significant (p>0.05). The decrease in vitamins and micronutrients that accompanies HIV infection suggests a potentially important role of nutritional supplementation and good nutrition in the proper management of HIV/AIDS. It is therefore recommended that HIV-infected Patients should be investigated and treated for micronutrients deficiency, to reduce the morbidity and mortality associated with HIV infection. Further studies should be carried out on other micronutrients and vitamins not covered in this study among HIV positive subjects.

Conflict of Interest

The authors declare that they have no conflict of interest.

Acknowledgement

The authors would like to acknowledge the management of Central Hospital, Uromi, Edo State, Edo State, Nigeria for creating the enabling environment for this study. Thanks to all the Laboratory and technical staff of St Kenny Research Consult, Ekpoma, Edo State, Nigeria for their excellent assistance and for providing medical writing/editorial support in accordance with Good Publication Practice (GPP3) guidelines.

Consent to Participate

Informed consent was obtained from each participant prior to specimen collection.

Financial Disclosure

This research did not receive any grant from funding agencies in the public, commercial or not-for-profit sectors.

Financial Disclosure

This research did not receive any grant from funding agencies in the public, commercial or not-for-profit sectors.

Financial Disclosure

This research did not receive any grant from funding agencies in the public, commercial or not-for-profit sectors.

Data Availability

Data is available for the journal. Informed consents were not necessary for this paper.

Author’s Contribution

The authors contributed equally.

References

1. Hymes KB, Cheung T, Greene JB, Prose NS, Marcus A. Ballard H. Kaposi’s sarcoma in homosexual men:A report of eight cases. Lancet, 2015;2(8247):598-600.
2. UNIADS/WHO Estimates. Summary of the global HIV epidemic 2023. [Last accessed on: November 17, 2024]

https://www.who.int/data/gho/data/themes/hiv-aids#:~:text=Globally%2C%2039.9%20million%20%5B36.1%E2%80%93,considerably%20between%20countries%20and%20regions

3. Cunningham A, Donahgy H, Harman A, Kim, M. Turville S. Manipulation of dendritic cell function by viruses. Current Opinion in Microbiology, 2010;13(4):524-9.
4. Iyevhobu KO, Obodo BN. Prevalence of Parasitic Infections in Relation to CD4+ and Antiretroviral(ART) Usage of HIV Sero-Positive Patients Attending Irrua Specialist Teaching Hospital (ISTH) Irrua, Edo State, Nigeria. Research and Reviews Journal of Microbiology and Biotechnology, 2020;1(2):34 – 41.
5. Babatope IO, Esumeh FI, Orhue PI, Iyevhobu KO. CD3, CD4 and CD8 Counts of Asymptomatic and Symptomatic HIV-1 Subjects in Irrua, Edo State, Nigeria. European Journal of Applied Sciences, 2022;10(3):744-764. DOI:DOI:10.14738/aivp.103.12533.
6. Lalit D, Nandini D. Clinical Manifestations of HIV infection. In:Baveja UK, Rewari BB(eds). Diagnosis and management of HIV/AIDS:a clinician’s perspective. 1st ed. New Delhi;BI Publications PVT Ltd:2014;63-79.
7. Costello C. Haematology in HIV disease. In:Hoffbrand AV, Catovsky D, Edward GDT(eds). Postgraduate Haematology. 5th ed. Massachusetts;Blackwell:2015;380-393.
8. Mehta S, Fawzi W. Effect of vitamins, including vitamin A on HIV/AIDS patients. Vitamins and Hormones, 2017;75(5):355-383.
9. Finamore A, Massimi M, Conti D, Mengheri E. Zinc deficiency induces membrane barrier damage and increases neutrophil transmigration in caco-2 cells. Journal of Nutrition, 2008;130(8):1664-1670.
10. Prasad AS. Zinc:mechanisms of host defense. Journal of Nutrition, 2007;13(7):1345-1349.
11. Prasad AS. Clinical, immunological, anti-inflammatory and antioxidant roles of zinc. Experimental Gerontology, 2008;4(3):370-377.
12. Kumar V, Choudhry VP. Iron deficiency and infection. Indian Journal of Pediatrics, 2010;77(7):789-793
13. Bhaskaram P. Micronutrient malnutrition, infection and immunity:an overview. Nutrition Reviews, 2002;60(2):40-45.
14. Nwokorie EA, Omolumen LE, Iyevhobu KO, Okogun GRA, Omolumen BA. Evaluation of Cardiovascular Risk Factors and Metabolic Abnormalities in HIV Subjects on Therapy. EC Microbiology, 2023;19(9):01-23.
15. Omolumen LE, Okogun GRA, Obodo BN, Iyevhobu KO, Idara IU, Ebaluegbeifoh LO, Unuane PO, Imodoye SO, Omisakin IA. Nutritional Indices of Human Immuno Deficiency Virus(HIV) and Tuberculosis(TB) Positive Pregnant Women. International Journal of Scientific and Research Publications, 2020;10(5):170-177.
16. Eley BS, Sive AA, Abelse L, Kossew G, Cooper M. Hussey GD. Growth and micronutrient disturbances in stable, HIV-infected children in Cape Town. Annals of Tropical Paediatrics, 2002;22(2):19-23.
17. Soldati L, Di-Renzo L, Jirillo E, Ascierto PA, Marincola FM, De-Lorenzo A. The influence of diet on anti-cancer immune responsiveness. Journal of Translational Medicine, 2018;16(3):75-80.
18. Omolumen LE, Iweka FK, Iyevhobu KO, Omolumen BA, Asibor E, Usiobeigbe OS, Ikede RE, Obohwemu KO, Adelakun AA, Owusuaa-Asante MA, Animasaun OP, Mabengban Yakpir, Adeji AJ, Karen Henry, Jamila Ally, Simran Koretaine, Abaku PO. Assessment of some Micronutrients of HIV Positive Subjects visiting Central Hospital, Edo State, Nigeria. Journal of Pharmaceutics and Drug Research, 2024;7(1):834-846.
19. Kwan CK, Eckhardt B, Baghdadi J, Aberg JA. Hyperparathyroidism and complications associated with vitamin D deficiency in HIV-infected adults in New York City. New York. AIDS Research and Human Retrovirus, 2022;28(9):1025-1032.
20. Kavitha K, Saharia GK, Singh AK, Mangaraj M. Association of serum vitamin B12 with immuno-hematological parameters in treatment-naive HIV positive cases. Journal of Family Medicine and Primary Care, 2022;11(7):3784-3789.
21. Grudzien M, Rapak A. Effect of natural compounds on NK cell activation. Journal of Immunology Research, 2018;18(9):486-488.
22. Gombart AF, Pierre A, Maggini S. A review of micronutrients and the immune system-working in harmony to reduce the risk of infection. Nutrients, 2020;12(2):236-239.
23. Yoshii K, Hosomi K, Sawane K, Kunisawa J. Metabolism of dietary and microbial vitamin B family in the regulation of host immunity. Frontiers in Nutrition, 2019;6(1):48-52.
24. Omolumen LE, Obodo BN, Iyevhobu KO, Idara IU, Irobonosen OI, Obi CC, Unuane PO, Eboiyehi IO, Edo EO. Assessment of Some Liver Enzymes of Human Immuno-Deficiency Virus(HIV) and Tuberculosis(TB) subjects in parts of Esan Land, Edo State. International Journal of Scientific and Research Publications, 2020b;10(4):688 – 696.
25. Cozzolino M, Vidal M, Arcidiacono MV, Tebas P, Yarasheski KE, Dusso AS. HIV-protease inhibitors impair vitamin D bioactivation to 1, 25-dihydroxy vitamin D. AIDS, 2023;17(4):513-520.
26. Wasserman P, Rubin DS. Highly prevalent vitamin D deficiency and insufficiency in an urban cohort of HIV-infected men under care. AIDS patient care and STDs, 2020;24(2):223-227.
27. Dao CN, Patel P, Overton ET, Rhame F, Pals SL, Johnson C, Bush, T, Brooks JT. 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. Clinical Infectious Dis. 2021;52(1):396-405.
28. Allavena C, Delpierre C, Cuzin L, Rey D, Viget N, Bernard J, et al. High frequency of vitamin D deficiency in HIV-infected patients:effects of HIV-related factors and antiretroviral drugs. J Antimicrobial and Chemotherapy. 2022;67(9):2222-30.
29. Okparaku SO, Agbakoba NR, Chukwuanukwu RC, Iyevhobu, KO, Okwelogu IS. Correlation Pattern of Selected Markers among Non-Naïve HIV Participants in Edo Central, Nigeria. In J Curr Microbiology and Applied Sci. 2024;13(04):97-106.
30. Knox TA, Spiegelman D, Skinner SC, Gorbach S. Diarrhea and abnormalities of gastrointestinal function in a cohort of men and women with HIV infection. American J Gastroenterol. 2020;91(5):3482-9.
31. Miller TL. Nutritional aspects of HIV-infected children receiving highly active antiretroviral therapy. AIDS. 2013;17(1):130-40.
32. Friis H, Michaelsen KF. Micronutrients and HIV infection:a review. European J Clinical Nutrition. 2018;52(3):157-63.
33. Tang AM, Graham MH, Kirby AJ, McCall LD, Willett WC, Saah AJ. Dietary micronutrient intake and risk of progression to acquired immunodeficiency syndrome(AIDS) in Human Immunodeficiency Virus type 1(HIV-1)-infected homosexual men. American J Epidemiol. 2016;138(11):937-51.
34. Baum MK, Shor-Posner G. Micronutrient status in relationship to mortality in HIV-1 disease. Nutr Rev. 2018;56(1):135-9.
35. Omolumen LE, Obodo BN, Iyevhobu KO, Okereke NP, Idara IU, Ebaluegbeifoh LO, et al. Evaluation of Lipid Profile of Human Immuno Deficiency Virus(HIV) and Tuberculosis(TB) Positive Pregnant Women. European J Biomedical and Pharmaceutical Sci. 2020;7(5):693-9.
36. Anyabolu HC, Adejuyigbe EA, Adeodu OO. Serum micronutrient status of Haart-Naïve, HIV infected children. A case control study. AIDS Research and Treatment, 2014;35(10):143147.
37. Nsonwu-Anyanwu AC, Egbe ER, Agu CE, Ofors SJ, Usoro CA, Essien IA. Nutritional indices and cardiovascular risk factors in HIV infection in Southern Nigeria. J Immunol and Microbiol. 2017;7(2):34-42.
38. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. American J Clinical Nutrition. 2018;68(4):447-64.
39. Bobat R, Coovadia H, Stephen C, Naidoo KL, Mckerrow N, Black RE. Safety and efficacy of zinc supplementation for children with HIV-I infection in South Africa:a randomized double-blind placebo-controlled trial. Lancet. 2015;3(66):1862-7.
40. Duggal S, Chugh TD, Duggal AK. HIV and malnutrition:effects on the immune system. Clinical Development and Immunol. 2018;12(2):245-8.
41. Wellinghausen N, Kern WV, Jochle W, Kern P. Zinc serum level in human immunodeficiency virus-infected patients in relation to immunological status. Biology and Element Res. 2020;7(3):139-49.
42. McLaren DS, Loveridge N, Duthie GG, Bolton-Smith C. Fat soluble vitamin. In: Garrow JS, James WPT, Human nutrition and dietetics. Churchill Livingstone Press, London. 2013;208-8.
43. Amare B, Tafess K, Moges F, Moges B, Yabutani T. Levels of serum zinc, copper and copper/zinc ratio in patients with diarrhea and HIV infection in Ethiopia. Vitamins and Trace Elements. 2021;11(2):125-30.
44. Graham NHM, Sorensen D, Odaka N, Brookmeyer R, Chan D. Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS. J Acquired Immune Deficiency Syndrome. 2011;4(1):976-80.
45. Moreno T, Artacho R, Navarro M, Perez A, Ruiz-Lopez MD. Serum copper concentration in HIV-infected patients and relationship with other biochemical indices. Science Total Environment. 2018;21(7):21-6.
46. Sunday Onyemaechi Okparaku, Regina Agbakoba, Rebecca Chinyelu Chukwuanukwu, Kenneth Oshiokhayamhe Iyevhobu. Variation blueprints: A prospective cohort study of chronic HIV infected subjects on HAART. World J Advanced Research and Rev. 2024b;21(03):1854-62.
47. Lawal S, Bilbis DB, Idowu YS, Mansur L, Chibueze HN. Serum levels of antioxidant vitamins and minerals elements of human immunodeficiency virus positive subjects in Sokoto, Nigeria. Annals of African Medicine. 2010;9(1):235-9.
48. Nwegbu MM, Egua MO, and Ogwu OS. Comparative study of plasma zinc and selenium levels amongst Human Immunodeficiency Virus (HIV) positive and negative subjects. African J Food Science and Technol. 2015;6(1):253-8.
49. Beisel WR. Trace elements in infectious process. North American Clinical Med. 2016;60(8):831-49.
50. Onyango AC, Walingo M, Othuon L. Food consumption patterns, diversity of food nutrients and mean nutrient intake in relation to HIV/AIDS status in Kisumu district Kenya. African J AIDS Res. 2019;8(3):359-66.
51. Dworkin B, Wormser BG, Rosenthal WS. Gastrointestinal manifestations of the acquired immunodeficiency syndrome: a review of 22 cases. American J Gastroenterol. 2015;80(10):774-8.
52. World Health Organization. Consultation on Nutrition and HIV/AIDS in Africa, Durban, South Africa. 2018.
53. Macallan DC. Nutrition and immune function in human immunodeficiency virus Infection. Proceedings of the Nutrition Soc. 2019;58(3):743-8.
54. Federal Ministry of Health. Federal Ministry of Health; Abuja, Nigeria:2018. National HIV sero-prevalence sentinel survey among pregnant women attending antenatal clinics in Nigeria. 2019. [Last accessed on: November 17, 2024]

http://www.nigeriaaids.org/documents/2010_National%20HIV%20Sero%20Prevalence%20Sentinel%20Survey.pdf