Skip to main content

Advertisement

SpringerLink
Log in

Undernutrition and HIV Infection in Sub-Saharan Africa: Health Outcomes and Therapeutic Interventions

  • Co-infections and Comorbidity (D Bhattacharya, Section Editor)
  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Sub-Saharan Africa (SSA) is disproportionately burdened by the twin epidemics of food insecurity and HIV infection, and protein-calorie undernutrition is common among persons with HIV (PWH) initiating antiretroviral therapy (ART) in the region. In this review, we discuss the intersection of HIV infection and undernutrition, health outcomes among undernourished PWH starting ART, and the demonstrated and potential benefits of therapeutic interventions such as micro/macronutrient supplementation and pharmacological agents.

Recent Findings

A low body mass index (BMI), used as a general indicator of poor nutrition in most studies, is associated with impaired immune recovery and increased mortality in the early ART period. The increased risk of mortality is multifactorial, and contributors include undernutrition-related immune system dysfunction, increased susceptibility to opportunistic infections, and metabolic and cardiovascular dysregulation. Clinical trials of micro/macronutrient supplementary feeding, appetite stimulants (hormones and anabolic agents), and recombinant adipokines have shown a benefit for weight gain and metabolic health, but there are few data on mortality or immune recovery.

Summary

A substantial proportion of PWH in SSA are undernourished, and undernutrition contributes to an increased risk of mortality and other adverse health outcomes. To date, there have been few prospective trials of nutritional supplementation and/or pharmacologic therapy among undernourished PWH in SSA, though findings from other settings suggest a potential benefit in this population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. The Joint United Nations Programme on HIV and AIDS. (2020). Global HIV and AIDS statistics - 2020 fact sheet. unaids.org/en/resources/fact-sheet.

  2. Coetzee D, Hildebrand K, Boulle A, Maartens G, Louis F, Labatala V, et al. Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa. AIDS. 2004;18:887–95.

    Article  PubMed  Google Scholar 

  3. Stringer, J. S. A., I. Zulu, J. Levy, E. M. Stringer, A. Mwango, B. H. Chi, V. Mtonga, S. Reid, R. A. Cantrell, M. Bulterys, M. S. Saag, R. G. Marlink, A. Mwinga, T. V Ellerbrock, and M. Sinkala. 2006. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA 296: 782–793.

  4. Ferradini, L., A. Jeannin, L. Pinoges, J. Izopet, D. Odhiambo, L. Mankhambo, G. Karungi, E. Szumilin, S. Balandine, G. Fedida, M. P. Carrieri, B. Spire, N. Ford, J.-M. Tassie, P. J. Guerin, and C. Brasher. 2006. Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment. Lancet (London, England) 367: 1335–1342.

  5. Calmy A, Pinoges L, Szumilin E, Zachariah R, Ford N, Ferradini L. Generic fixed-dose combination antiretroviral treatment in resource-poor settings: multicentric observational cohort. AIDS. 2006;20:1163–9.

    Article  PubMed  Google Scholar 

  6. Moosa A, Gengiah TN, Lewis L, Naidoo K. Long-term adherence to antiretroviral therapy in a South African adult patient cohort: a retrospective study. BMC Infect Dis. 2019;19:775.

    Article  PubMed  PubMed Central  Google Scholar 

  7. World Health Organization. (2018). HIV/AIDS disease burden in the Africa region. Afro.who.int/health-topics/hivaids.

  8. Johannessen A, Naman E, Ngowi BJ, Sandvik L, Matee MI, Aglen HE, et al. Predictors of mortality in HIV-infected patients starting antiretroviral therapy in a rural hospital in Tanzania. BMC Infect Dis. 2008;8:52.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zachariah R, Fitzgerald M, Massaquoi M, Pasulani O, Arnould L, Makombe S, et al. Risk factors for high early mortality in patients on antiretroviral treatment in a rural district of Malawi. AIDS. 2006;20:2355–60.

    Article  PubMed  Google Scholar 

  10. Ivers LC, Cullen KA, Freedberg KA, Block S, Coates J, Webb P. HIV/AIDS, undernutrition, and food insecurity. Clin Infect Dis. 2009;49:1096–102.

    Article  PubMed  Google Scholar 

  11. Schönfeldt HC, Gibson Hall N. Dietary protein quality and malnutrition in Africa. Br J Nutr. 2012;108:S69–76.

    Article  PubMed  Google Scholar 

  12. Iyer SS, Chatraw JH, Tan WG, Wherry EJ, Becker TC, Ahmed R, et al. Protein energy malnutrition impairs homeostatic proliferation of memory CD8 T cells. J Immunol. 2012;188:77–84.

    Article  CAS  PubMed  Google Scholar 

  13. Webb P, Stordalen GA, Singh S, Wijesinha-Bettoni R, Shetty P, Lartey A. Hunger and malnutrition in the 21st century. BMJ. 2018;361.

  14. Grover Z, Ee LC. Protein energy malnutrition. Pediatr Clin N Am. 2009;56:1055–68.

    Article  Google Scholar 

  15. Anríquez, G., P. Karfakis, S. Daidone, and E. Mane. Measuring dietary energy deficiency and the impact of food price variations at the household level: a methodological note on the micro-analysis of undernourishment,.

  16. 2003. The “MUST” explanatory booklet : a guide to the ‘Malnutrition Universal Screening Tool’ (“MUST”) for adults , (V. Todorovic, ed). BAPEN, Redditch.

  17. Koethe JR, Limbada MI, Giganti MJ, Nyirenda CK, Mulenga L, Wester CW, et al. Early immunologic response and subsequent survival among malnourished adults receiving antiretroviral therapy in Urban Zambia. AIDS. 2010;24:2117–21.

    Article  PubMed  Google Scholar 

  18. Duggal S, Das Chugh T, Duggal AK. HIV and malnutrition: effects on immune system. Clin Dev Immunol. 2012;2012:784740.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Chandra RK. Numerical and functional deficiency in T helper cells in protein energy malnutrition. Clin Exp Immunol. 1983;51:126–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Keithley JK, Swanson B. HIV-associated wasting. J Assoc Nurses AIDS Care. 2013;24:S103–11.

    Article  PubMed  Google Scholar 

  21. Wanke, C. 2004. Pathogenesis and consequences of HIV-associated wasting JAIDS J Acquir Immune Defic Syndr 37.

  22. Castro, G. K., Ward, J.W., Slutsker, L. Buehler, J.W., Jaffe J.W., Berkelman, R.L. Curran, J. W. 1993. Revised Classification System for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults,.

    Google Scholar 

  23. Powanda MC, Beisel WR. Metabolic effects of infection on protein and energy status. J Nutr. 2003;133:322S–7S.

    Article  PubMed  Google Scholar 

  24. Roubenoff R, Grinspoon S, Skolnik PR, Tchetgen E, Abad L, Spiegelman D, et al. Role of cytokines and testosterone in regulating lean body mass and resting energy expenditure in HIV-infected men. Am J Physiol Endocrinol Metab. 2002;283:E138–45.

    Article  CAS  PubMed  Google Scholar 

  25. Macallan DC, Noble C, Baldwin C, Jebb SA, Prentice AM, Coward WA, et al. Energy expenditure and wasting in human immunodeficiency virus infection. N Engl J Med. 1995;333:83–8.

    Article  CAS  PubMed  Google Scholar 

  26. Batman PA, Miller AR, Forster SM, Harris JR, Pinching AJ, Griffin GE. Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology. J Clin Pathol. 1989;42:275–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Koethe JR, Heimburger DC. Nutritional aspects of HIV-associated wasting in sub-Saharan Africa. Am J Clin Nutr. 2010;91:1138S–42S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Uthman OA. Prevalence and pattern of HIV-related malnutrition among women in sub-Saharan Africa: a meta-analysis of demographic health surveys. BMC Public Health. 2008;8:226.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Koethe JR, Lukusa A, Giganti MJ, Chi BH, Nyirenda CK, Limbada MI, et al. Association between weight gain and clinical outcomes among malnourished adults initiating antiretroviral therapy in Lusaka. Zambia J Acquir Immune Defic Syndr. 2010;53:507–13.

    Article  PubMed  Google Scholar 

  30. Naidoo K, Yende-Zuma N, Augustine S. A retrospective cohort study of body mass index and survival in HIV infected patients with and without TB co-infection. Infect Dis Poverty. 2018;7:35.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Silverman RA, John-Stewart GC, Beck IA, Milne R, Kiptinness C, McGrath CJ, et al. Predictors of mortality within the first year of initiating antiretroviral therapy in urban and rural Kenya: A prospective cohort study. PLoS One. 2019;14:e0223411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Okoye AA, Picker LJ. CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure. Immunol Rev. 2013;254:54–64.

    Article  PubMed  PubMed Central  Google Scholar 

  33. McCune JM. The dynamics of CD4+ T-cell depletion in HIV disease. Nature. 2001;410:974–9.

    Article  CAS  PubMed  Google Scholar 

  34. Vidya Vijayan KK, Karthigeyan KP, Tripathi SP, Hanna LE. Pathophysiology of CD4+ T-Cell Depletion in HIV-1 and HIV-2 Infections. Front Immunol. 2017;8:580.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Palermo B, Bosch RJ, Bennett K, Jacobson JM. Body mass index and CD4+ T-lymphocyte recovery in HIV-infected men with viral suppression on antiretroviral therapy. HIV Clin Trials. 2011;12:222–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Koethe JR, Jenkins CA, Lau B, Shepherd BE, Wester W, Rebeiro PF, et al. Higher time-updated body mass index: association with improved CD4+ cell recovery on HIV treatment. J Acquir Immune Defic Syndr. 2016;73:197–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. •• Li, X., H. Ding, W. Geng, J. Liu, Y. Jiang, J. Xu, Z. Zhang, and H. Shang. Predictive effects of body mass index on immune reconstitution among HIV-infected HAART users in China. BMC Infect. Dis. 2019;19:373. This article determined that PWH with a higher baseline BMI had higher rates of CD4 reconstitution after initiating ART therapy compared to PWH with a lower baseline BMI.

  38. Paton NI, Sangeetha S, Earnest A, Bellamy R. The impact of malnutrition on survival and the CD4 count response in HIV-infected patients starting antiretroviral therapy. HIV Med. 2006;7:323–30.

    Article  CAS  PubMed  Google Scholar 

  39. Chisenga CC, Filteau S, Siame J, Chisenga M, Prendergast AJ, Kelly P. T-cell subsets predict mortality in malnourished Zambian adults initiating antiretroviral therapy. PLoS One. 2015;10:e0129928.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Koethe JR, Heimburger DC, PrayGod G, Filteau S. From wasting to obesity: the contribution of nutritional status to immune activation in HIV infection. J Infect Dis. 2016;214(Suppl):S75–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Benzekri NA, Sambou J, Diaw B, Sall EHI, Sall F, Niang A, et al. High prevalence of severe food insecurity and malnutrition among HIV-infected adults in Senegal, West Africa. PLoS One. 2015;10:e0141819.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Musumari PM, Wouters E, Kayembe PK, Kiumbu Nzita M, Mbikayi SM, Suguimoto SP, et al. Food insecurity is associated with increased risk of non-adherence to antiretroviral therapy among HIV-infected adults in the Democratic Republic of Congo: a cross-sectional study. PLoS One. 2014;9:e85327.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Becker N, Cordeiro LS, Poudel KC, Sibiya TE, Sayer AG, Sibeko LN. Individual, household, and community level barriers to ART adherence among women in rural Eswatini. PLoS One. 2020;15:e0231952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Heimburger DC, Koethe JR, Nyirenda C, Bosire C, Chiasera JM, Blevins M, et al. Serum phosphate predicts early mortality in adults starting antiretroviral therapy in Lusaka, Zambia: a prospective cohort study. PLoS One. 2010;5:e10687.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Koethe JR, Blevins M, Nyirenda CK, Kabagambe EK, Chiasera JM, Shepherd BE, et al. Serum phosphate predicts early mortality among underweight adults starting ART in Zambia: a novel context for refeeding syndrome? J Nutr Metab. 2013;2013:545439.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Koethe JR, Blevins M, Nyirenda C, Kabagambe EK, Shepherd BE, Wester CW, et al. Nutrition and inflammation serum biomarkers are associated with 12-week mortality among malnourished adults initiating antiretroviral therapy in Zambia. J Int AIDS Soc. 2011;14:19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Reynolds, J. V, C. O’Farrelly, C. Feighery, P. Murchan, N. Leonard, G. Fulton, C. O’Morain, F. B. Keane, and W. A. Tanner. 1996. Impaired gut barrier function in malnourished patients. Br J Surg 83: 1288–1291.

  48. Welsh, F. K., S. M. Farmery, K. MacLennan, M. B. Sheridan, G. R. Barclay, P. J. Guillou, and J. V Reynolds. 1998. Gut barrier function in malnourished patients. Gut 42: 396–401.

  49. Carbonnel F, Beaugerie L, Abou Rached A, D’Almagne H, Rozenbaum W, Le Quintrec Y, et al. Macronutrient intake and malabsorption in HIV infection: a comparison with other malabsorptive states. Gut. 1997;41:805–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gori A, Tincati C, Rizzardini G, Torti C, Quirino T, Haarman M, et al. Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis. J Clin Microbiol. 2008;46:757–8.

    Article  PubMed  Google Scholar 

  51. Crakes KR, Jiang G. Gut microbiome alterations during HIV/SIV infection: implications for HIV cure. Front Microbiol. 2019;10:1104.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Canipe A, Chidumayo T, Blevins M, Bestawros M, Bala J, Kelly P, et al. A 12 week longitudinal study of microbial translocation and systemic inflammation in undernourished HIV-infected Zambians initiating antiretroviral therapy. BMC Infect Dis. 2014;14:521.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Bestawros M, Chidumayo T, Blevins M, Canipe A, Bala J, Kelly P, et al. Increased systemic inflammation is associated with cardiac and vascular dysfunction over the first 12 weeks of antiretroviral therapy among undernourished, HIV-infected adults in Southern Africa. J AIDS Clin Res. 2015;6:431.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Schwenk A, Buger B, Wessel D, Stutzer H, Ziegenhagen D, Diehl V, et al. Clinical risk factors for malnutrition in HIV-1-infected patients. AIDS. 1993;7:1213–9.

    Article  CAS  PubMed  Google Scholar 

  55. Kublin, J. G., P. Patnaik, C. S. Jere, W. C. Miller, I. F. Hoffman, N. Chimbiya, R. Pendame, T. E. Taylor, and M. E. Molyneux. 2005. Effect of Plasmodium falciparum malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: a prospective cohort study. Lancet (London, England) 365: 233–240.

  56. Swaminathan S, Padmapriyadarsini C, Sukumar B, Iliayas S, Kumar SR, Triveni C, et al. Nutritional status of persons with HIV infection, persons with HIV infection and tuberculosis, and HIV-negative individuals from southern India. Clin Infect Dis. 2008;46:946–9.

    Article  PubMed  Google Scholar 

  57. Kawai K, Villamor E, Mugusi FM, Saathoff E, Urassa W, Bosch RJ, et al. Predictors of change in nutritional and hemoglobin status among adults treated for tuberculosis in Tanzania. Int J Tuberc lung Dis Off J Int Union against Tuberc Lung Dis. 2011;15:1380–9.

    CAS  Google Scholar 

  58. Benzekri NA, Sambou JF, Tamba IT, Diatta JP, Sall I, Cisse O, et al. Nutrition support for HIV-TB co-infected adults in Senegal, West Africa: a randomized pilot implementation study. PLoS One. 2019;14:e0219118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ezeamama AE, Mupere E, Oloya J, Martinez L, Kakaire R, Yin X, et al. Age, sex, and nutritional status modify the CD4+ T-cell recovery rate in HIV-tuberculosis co-infected patients on combination antiretroviral therapy. Int J Infect Dis IJID Off Publ Int Soc Infect Dis. 2015;35:73–9.

    CAS  Google Scholar 

  60. Buchacz K, Patel P, Taylor M, Kerndt PR, Byers RH, Holmberg SD, et al. Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected patients with new syphilis infections. AIDS. 2004;18:2075–9.

    Article  PubMed  Google Scholar 

  61. Nagot N, Ouedraogo A, Foulongne V, Konate I, Weiss HA, Vergne L, et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. 2007;356:790–9.

    Article  CAS  PubMed  Google Scholar 

  62. Stete, K., T. R. Glass, G. J. van Dam, A. Ntamatungiro, E. Letang, C. J. de Dood, P. L. A. M. Corstjens, R. Ndege, H. Mapesi, W. V Kern, C. Hatz, M. Weisser, J. Utzinger, and M. C. Muller. 2018. Effect of schistosomiasis on the outcome of patients infected with HIV-1 starting antiretroviral therapy in rural Tanzania. PLoS Negl Trop Dis 12: e0006844.

  63. Wall KM, Kilembe W, Vwalika B, Dinh C, Livingston P, Lee Y-M, et al. Schistosomiasis is associated with incident HIV transmission and death in Zambia. PLoS Negl Trop Dis. 2018;12:e0006902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Walson, J. L., B. R. Herrin, and G. John-Stewart. 2009. Deworming helminth co-infected individuals for delaying HIV disease progression. Cochrane database Syst. Rev. CD006419–CD006419.

  65. Means, A. R., P. Burns, D. Sinclair, and J. L. Walson. 2016. Antihelminthics in helminth-endemic areas: effects on HIV disease progression. Cochrane database Syst. Rev. 4: CD006419.

  66. Batool R, Butt MS, Sultan MT, Saeed F, Naz R. Protein-energy malnutrition: a risk factor for various ailments. Crit Rev Food Sci Nutr. 2015;55:242–53.

    Article  PubMed  Google Scholar 

  67. Smythe, P. M., G. G. Brereton-Stiles, H. J. Grace, A. Mafoyane, M. Schonland, H. M. Coovadia, W. E. Loening, M. A. Parent, and G. H. Vos. 1971. Thymolymphatic deficiency and depression of cell-mediated immunity in protein-calorie malnutrition. Lancet (London, England) 2: 939–943.

  68. Ozkale M, Sipahi T. Hematologic and bone marrow changes in children with protein-energy malnutrition. Pediatr Hematol Oncol. 2014;31:349–58.

    Article  CAS  PubMed  Google Scholar 

  69. Ibrahim MK, Zambruni M, Melby CL, Melby PC. Impact of childhood malnutrition on host defense and infection. Clin Microbiol Rev. 2017;30:919–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. McGettrick AF, O’Neill LAJ. How metabolism generates signals during innate immunity and inflammation. J Biol Chem. 2013;288:22893–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Bourke CD, Berkley JA, Prendergast AJ. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol. 2016;37:386–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ramsay G, Cantrell D. Environmental and metabolic sensors that control T cell biology. Front Immunol. 2015;6:99.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Ma EH, Poffenberger MC, Wong AH-T, Jones RG. The role of AMPK in T cell metabolism and function. Curr Opin Immunol. 2017;46:45–52.

    Article  CAS  PubMed  Google Scholar 

  74. Saravia J, Raynor JL, Chapman NM, Lim SA, Chi H. Signaling networks in immunometabolism. Cell Res. 2020;30:328–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Palmer CS, Hussain T, Duette G, Weller TJ, Ostrowski M, Sada-Ovalle I, et al. Regulators of glucose metabolism in CD4(+) and CD8(+) T cells. Int Rev Immunol. 2016;35:477–88.

    Article  CAS  PubMed  Google Scholar 

  76. MacIver NJ, Michalek RD, Rathmell JC. Metabolic regulation of T lymphocytes. Annu Rev Immunol. 2013;31:259–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Murray, P. J., J. Rathmell, and E. Pearce. 2015. SnapShot: immunometabolism. Cell Metab. 22: 190-190.e1.

  78. Saucillo DC, Gerriets VA, Sheng J, Rathmell JC, Maciver NJ. Leptin metabolically licenses T cells for activation to link nutrition and immunity. J Immunol. 2014;192:136–44.

    Article  CAS  PubMed  Google Scholar 

  79. Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15:930–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Palmer CS, Ostrowski M, Gouillou M, Tsai L, Yu D, Zhou J, et al. Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection. AIDS. 2014;28:297–309.

    Article  CAS  PubMed  Google Scholar 

  81. Palmer CS, Anzinger JJ, Zhou J, Gouillou M, Landay A, Jaworowski A, et al. Glucose transporter 1-expressing proinflammatory monocytes are elevated in combination antiretroviral therapy-treated and untreated HIV+ subjects. J Immunol. 2014;193:5595–603.

    Article  CAS  PubMed  Google Scholar 

  82. •• Masson, J. J. R., A. J. Murphy, M. K. S. Lee, M. Ostrowski, S. M. Crowe, and C. S. Palmer. 2017. Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy. PLoS One 12: e0183931. This article investigates the immunometabolic consequences of HIV infection on CD4+ and CD8+ T cell function, and its potential influence on the development of metabolic disregylation in PWH.

  83. Sena LA, Li S, Jairaman A, Prakriya M, Ezponda T, Hildeman DA, et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity. 2013;38:225–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006;6:772–83.

    Article  CAS  PubMed  Google Scholar 

  85. Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005;115:911–9 quiz 920.

    Article  CAS  PubMed  Google Scholar 

  86. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.

    Article  CAS  PubMed  Google Scholar 

  87. Al-Fadhli M, Saraya M, Qasem J, Azizieh F, Shahab S, Raghupathy R. Relationship between leptin levels and suppressed CD4 counts in HIV patients. Med Princ Pract. 2013;22:54–8.

    Article  PubMed  Google Scholar 

  88. ONYEMELUKWE GC, OGOINA D, BAKARI AG. Serum leptin levels in antiretroviral therapy naïve HIV-1 infected patients in Zaria. Nigeria Int J Endocrinol Metab. 2009;7:162–9.

    CAS  Google Scholar 

  89. Tiliscan C, Aramă V, Mihăilescu R, Munteanu DI, Streinu-Cercel A, Ion DA, et al. Leptin expression in HIV-infected patients during antiretroviral therapy. Germs. 2015;5:92–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Farooqi IS, O’Rahilly S. 20 years of leptin: human disorders of leptin action. J Endocrinol. 2014;223:T63–70.

    Article  CAS  PubMed  Google Scholar 

  91. SÁNCHEZ-MARGALET, V., C. MARTÍN-ROMERO, C. GONZÁLEZ-YANES, R. GOBERNA, J. RODRÍGUEZ-BAÑO, and M. A. MUNIAIN. 2002. Leptin receptor (Ob-R) expression is induced in peripheral blood mononuclear cells by in vitro activation and in vivo in HIV-infected patients. Clin Exp Immunol 129: 119–124.

  92. Bennett BD, Solar GP, Yuan JQ, Mathias J, Thomas GR, Matthews W. A role for leptin and its cognate receptor in hematopoiesis. Curr Biol. 1996;6:1170–80.

    Article  CAS  PubMed  Google Scholar 

  93. Moraes-Vieira PMM, Larocca RA, Bassi EJ, Peron JPS, Andrade-Oliveira V, Wasinski F, et al. Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory T and Th17 cells. Eur J Immunol. 2014;44:794–806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Mattioli B, Straface E, Quaranta MG, Giordani L, Viora M. Leptin promotes differentiation and survival of human dendritic cells and licenses them for Th1 priming. J Immunol. 2005;174:6820–8.

    Article  CAS  PubMed  Google Scholar 

  95. Batra A, Okur B, Glauben R, Erben U, Ihbe J, Stroh T, et al. Leptin: a critical regulator of CD4+ T-cell polarization in vitro and in vivo. Endocrinology. 2010;151:56–62.

    Article  CAS  PubMed  Google Scholar 

  96. Gerriets VA, Danzaki K, Kishton RJ, Eisner W, Nichols AG, Saucillo DC, et al. Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity. Eur J Immunol. 2016;46:1970–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Jaedicke KM, Roythorne A, Padget K, Todryk S, Preshaw PM, Taylor JJ. Leptin up-regulates TLR2 in human monocytes. J Leukoc Biol. 2013;93:561–71.

    Article  CAS  PubMed  Google Scholar 

  98. Kim S-J. Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-α in monocyte-derived macrophages. J Periodontal Implant Sci. 2010;40:119–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Jitprasertwong P, Jaedicke KM, Nile CJ, Preshaw PM, Taylor JJ. Leptin enhances the secretion of interleukin (IL)-18, but not IL-1β, from human monocytes via activation of caspase-1. Cytokine. 2014;65:222–30.

    Article  CAS  PubMed  Google Scholar 

  100. Koethe JR, Chi BH, Megazzini KM, Heimburger DC, Stringer JSA. Macronutrient supplementation for malnourished HIV-infected adults: a review of the evidence in resource-adequate and resource-constrained settings. Clin Infect Dis. 2009;49:787–98.

    Article  PubMed  Google Scholar 

  101. Madec Y, Szumilin E, Genevier C, Ferradini L, Balkan S, Pujades M, et al. Weight gain at 3 months of antiretroviral therapy is strongly associated with survival: evidence from two developing countries. AIDS. 2009;23:853–61.

    Article  PubMed  Google Scholar 

  102. Cantrell RA, Sinkala M, Megazinni K, Lawson-Marriott S, Washington S, Chi BH, et al. A pilot study of food supplementation to improve adherence to antiretroviral therapy among food-insecure adults in Lusaka. Zambia J Acquir Immune Defic Syndr. 2008;49:190–5.

    Article  PubMed  Google Scholar 

  103. Tirivayi N, Koethe JR, Groot W. Clinic-based food assistance is associated with increased medication adherence among HIV-infected adults on long-term antiretroviral therapy in Zambia. J AIDS Clin Res. 2012;3:171.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Visser J, McLachlan MH, Maayan N, Garner P. Community-based supplementary feeding for food insecure, vulnerable and malnourished populations – an overview of systematic reviews. Cochrane Database Syst Rev. 2018.

  105. Ndekha MJ, van Oosterhout JJG, Zijlstra EE, Manary M, Saloojee H, Manary MJ. Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: randomised, investigator blinded, controlled trial. BMJ. 2009;338:b1867.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Tshingani, K., P. Donnen, H. Mukumbi, P. Duez, and M. Dramaix-Wilmet. 2017. Impact of Moringa oleifera lam. Leaf powder supplementation versus nutritional counseling on the body mass index and immune response of HIV patients on antiretroviral therapy: a single-blind randomized control trial. BMC Complement. Altern. Med. 17: 420.

  107. Mallewa J, Szubert AJ, Mugyenyi P, Chidziva E, Thomason MJ, Chepkorir P, et al. Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial. lancet. HIV. 2018;5:e231–40.

    PubMed  Google Scholar 

  108. Koethe JR, Marseille E, Giganti MJ, Chi BH, Heimburger D, Stringer JS. Estimating the cost-effectiveness of nutrition supplementation for malnourished, HIV-infected adults starting antiretroviral therapy in a resource-constrained setting. Cost Eff Resour Alloc. 2014;12:10.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Woodd SL, Kelly P, Koethe JR, Praygod G, Rehman AM, Chisenga M, et al. Risk factors for mortality among malnourished HIV-infected adults eligible for antiretroviral therapy. BMC Infect Dis. 2016;16:562.

    Article  PubMed  PubMed Central  Google Scholar 

  110. PrayGod G, Blevins M, Woodd S, Rehman AM, Jeremiah K, Friis H, et al. A longitudinal study of systemic inflammation and recovery of lean body mass among malnourished HIV-infected adults starting antiretroviral therapy in Tanzania and Zambia. Eur J Clin Nutr. 2016;70:499–504.

    Article  CAS  PubMed  Google Scholar 

  111. Koethe JR, Blevins M, Bosire C, Nyirenda C, Kabagambe EK, Mwango A, et al. Self-reported dietary intake and appetite predict early treatment outcome among low-BMI adults initiating HIV treatment in sub-Saharan Africa. Public Health Nutr. 2013;16:549–58.

    Article  PubMed  Google Scholar 

  112. Rehman AM, Woodd S, PrayGod G, Chisenga M, Siame J, Koethe JR, et al. Effects on anthropometry and appetite of vitamins and minerals given in lipid nutritional supplements for malnourished HIV-infected adults referred for antiretroviral therapy: results from the NUSTART randomized controlled trial. J Acquir Immune Defic Syndr. 2015;68:405–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Rehman AM, Woodd SL, Heimburger DC, Koethe JR, Friis H, PrayGod G, et al. Changes in serum phosphate and potassium and their effects on mortality in malnourished African HIV-infected adults starting antiretroviral therapy and given vitamins and minerals in lipid-based nutritional supplements: secondary analysis from the Nutrit. Br J Nutr. 2017;117:814–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Badowski ME, Perez SE. Clinical utility of dronabinol in the treatment of weight loss associated with HIV and AIDS. HIV AIDS (Auckl). 2016;8:37–45.

    CAS  Google Scholar 

  115. Kaore SN, Langade DK, Yadav VK, Sharma P, Thawani VR, Sharma R. Novel actions of progesterone: what we know today and what will be the scenario in the future? J Pharm Pharmacol. 2012;64:1040–62.

    Article  CAS  PubMed  Google Scholar 

  116. Von Roenn JH, Murphy RL, Wegener N. Megestrol acetate for treatment of anorexia and cachexia associated with human immunodeficiency virus infection. Semin Oncol. 1990;17:13–6.

    Google Scholar 

  117. Oster. 1. Oster, M. H., S. R. Enders, S. J. Samuels, L. A. Cone, T. M. Hooton, H. P. Browder, and N. M. Flynn. 1994. Megestrol acetate in patients with AIDS and cachexia. Ann Intern Med 121: 400–408.

  118. Von Roenn JH. Randomized trials of megestrol acetate for AIDS-associated anorexia and cachexia. Oncology. 1994;51(Suppl 1):19–24.

    Article  Google Scholar 

  119. Von Roenn JH, Armstrong D, Kotler DP, Cohn DL, Klimas NG, Tchekmedyian NS, et al. Megestrol acetate in patients with AIDS-related cachexia. Ann Intern Med. 1994;121:393–9.

    Article  Google Scholar 

  120. Badowski ME, Yanful PK. Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer. Ther Clin Risk Manag. 2018;14:643–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Timpone JG, Wright DJ, Li N, Egorin MJ, Enama ME, Mayers J, et al. The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. AIDS Res. Hum. Retroviruses. 1997;13:305–15.

    Article  CAS  Google Scholar 

  122. Dobs A. Role of testosterone in maintaining lean body mass and bone density in HIV-infected patients. Int J Impot Res. 2003;15:S21–5.

    Article  CAS  PubMed  Google Scholar 

  123. Mulligan K, Zackin R, Von Roenn JH, Chesney MA, Egorin MJ, Sattler FR, et al. Testosterone supplementation of megestrol therapy does not enhance lean tissue accrual in men with human immunodeficiency virus-associated weight loss: a randomized, double-blind, placebo-controlled, multicenter trial. J Clin Endocrinol Metab. 2007;92:563–70.

    Article  CAS  PubMed  Google Scholar 

  124. Wong N, Levy M, Stephenson I. Hypogonadism in the HIV-infected man. Curr Treat Options Infect Dis. 2017;9:104–16.

    Article  PubMed  PubMed Central  Google Scholar 

  125. Bhasin S, Storer TW, Asbel-Sethi N, Kilbourne A, Hays R, Sinha-Hikim I, et al. Effects of testosterone replacement with a nongenital, transdermal system, Anoderm, in human immunodeficiency virus-infected men with low testosterone levels. J Clin Endocrinol Metab. 1998;83:3155–62.

    CAS  PubMed  Google Scholar 

  126. Zhou T, Hu Z-Y, Zhang H-P, Zhao K, Zhang Y, Li Y, et al. Effects of testosterone supplementation on body composition in HIV patients: a meta-analysis of double-blinded randomized controlled trials. Curr Med Sci. 2018;38:191–8.

    Article  CAS  PubMed  Google Scholar 

  127. Choi HH, Gray PB, Storer TW, Calof OM, Woodhouse L, Singh AB, et al. Effects of testosterone replacement in human immunodeficiency virus-infected women with weight loss. J Clin Endocrinol Metab. 2005;90:1531–41.

    Article  CAS  PubMed  Google Scholar 

  128. Badowski M, Pandit NS. Pharmacologic management of human immunodeficiency virus wasting syndrome. Pharmacotherapy. 2014;34:868–81.

    Article  PubMed  Google Scholar 

  129. Schambelan M, Mulligan K, Grunfeld C, Daar ES, LaMarca A, Kotler DP, et al. Recombinant human growth hormone in patients with HIV-associated wasting. A randomized, placebo-controlled trial. Serostim Study Group. Ann Intern Med. 1996;125:873–82.

    Article  CAS  PubMed  Google Scholar 

  130. Wensveen FM, Valentić S, Šestan M, Wensveen TT, Polić B. Interactions between adipose tissue and the immune system in health and malnutrition. Semin Immunol. 2015;27:322–33.

    Article  CAS  PubMed  Google Scholar 

  131. Paganelli, R., I. Mezzaroma, A. M. Mazzone, E. Pinter, and F. Aiuti. 1999. Leptin levels in HIV-positive patients treated with HAART AIDS 13.

  132. Nagy GS, Tsiodras S, Martin LD, Avihingsanon A, Gavrila A, Hsu WC, et al. Human immunodeficiency virus type 1-related lipoatrophy and lipohypertrophy are associated with serum concentrations of leptin. Clin Infect Dis. 2003;36:795–802.

    Article  CAS  PubMed  Google Scholar 

  133. Foo J-P, Mantzoros CS. Leptin in congenital or HIV-associated lipodystrophy and metabolic syndrome: a need for more mechanistic studies and large, randomized, placebo-controlled trials. Metabolism. 2012;61:1331–6.

    Article  CAS  PubMed  Google Scholar 

  134. Mulligan K, Khatami H, Schwarz J-M, Sakkas GK, DePaoli AM, Tai VW, et al. The effects of recombinant human leptin on visceral fat, dyslipidemia, and insulin resistance in patients with human immunodeficiency virus-associated lipoatrophy and hypoleptinemia. J Clin Endocrinol Metab. 2009;94:1137–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Lee JH, Chan JL, Sourlas E, Raptopoulos V, Mantzoros CS. Recombinant Methionyl Human Leptin Therapy in Replacement Doses Improves Insulin Resistance and Metabolic Profile in Patients with Lipoatrophy and Metabolic Syndrome Induced by the Highly Active Antiretroviral Therapy. J Clin Endocrinol Metab. 2006;91:2605–11.

    Article  CAS  PubMed  Google Scholar 

Download references

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana

    Hubaida Fuseini, Ben A. Gyan & George B. Kyei

  2. Department of Virology, Noguchi Memorial Institute for Medical Research, Legon, Ghana

    Hubaida Fuseini, Ben A. Gyan & George B. Kyei

  3. Divison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, 37232-2582, USA

    Hubaida Fuseini & John R. Koethe

  4. Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA

    George B. Kyei

  5. Vanderbilt Institute for Global Health, Nashville, TN, USA

    Douglas C. Heimburger & John R. Koethe

Authors
  1. Hubaida Fuseini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ben A. Gyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George B. Kyei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Douglas C. Heimburger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John R. Koethe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hubaida Fuseini.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Co-infections and Comorbidity

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fuseini, H., Gyan, B.A., Kyei, G.B. et al. Undernutrition and HIV Infection in Sub-Saharan Africa: Health Outcomes and Therapeutic Interventions. Curr HIV/AIDS Rep 18, 87–97 (2021). https://doi.org/10.1007/s11904-021-00541-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11904-021-00541-6

Keywords

Search

Navigation