**6. Conclusion**

*Nutrition and HIV/AIDS - Implication for Treatment, Prevention and Cure*

in their Peyer's patches [123, 124].

blunts antibody response to immunisation [97].

HIV infection also has a direct impact on nutrition. Studies have shown that among asymptomatic HIV-positive children, the rates of protein, carbohydrate and fat malabsorption are 30–60, 32 and 30%, respectively [127, 128]. Increased protein turnover occurs to cater for proliferation of neutrophils, fibroblasts and lymphocytes, production of immunoglobulins and acute-phase reactants and increased urinary nitrogen loss. This mainly comes from increased skeletal muscle breakdown and increased hepatic protein synthesis. Other metabolic changes that occur include elevated hepatic fatty acid synthesis, decreased peripheral lipoprotein lipase activity, hypertriglyceridemia, increased gluconeogenesis, insulin resistance and hyperglycaemia. There is redistribution of body stores of iron and zinc, with both being mobilised to the liver. This along with inadequate dietary intake leads to iron and

mice show a poor IgG response which is reversible by vitamin A supplementation. Vitamin A-deficient mice also have decreased number of IgA-secreting plasma cells

Levels of CD4+ and CD8+ cells in peripheral blood remain unaltered in malnourished children hospitalised with serious infections. But there is a decrease in the number of CD4+ CD45RO+ memory T cells and effector T cells (CD4+ CD62L− and CD8+ CD28−) in severe malnutrition. Th1 cytokines required for Th1 differentiation (IL-7, IL-12, IL-18 and IL-21) and function (IL-2 and IFN-γ) are reduced in peripheral blood mononuclear cells of children with malnutrition and severe infection. In the same children, an overexpression of Th2 cytokines (IL-4 and IL-10) and increased apoptosis of CD3+ T cells is noted. The ability of T cells to respond to an inflammatory stimulus is also altered. There is an impaired antigen-specific T-cell response (decreased CD8+ cells and decreased IL-2 production by CD4+ cells), but antigen-specific antibody production is unimpaired. Proliferative response to phytohaemagglutinin is reduced. Delayed-type hypersensitivity response is also impaired in severe malnutrition. Zinc is required for Th1 differentiation and Th1 responses. It increases expression of IL-2, IFN-γ and IL-2Rb β2. Zinc deficiency therefore results in a reduction of CD4/CD8 ratio and levels of Th1 cytokines. Selenium deficiency adversely affects CD4+ T-cell proliferation, activation and function. The production of IL-2 and expression of IL-2 receptor are both reduced, and there is impaired mobilisation of calcium. Retinoic acid acts on naive T cells and promotes expression of gut-homing receptors, differentiation into Th2 phenotype and T-regulatory cells especially in the gut mucosa. It also inhibits maturation to Th1 phenotype or Th17 cells. RA activates B cells in mucosa and GALT to transform into IgA+ antibody secreting cells (ASC). Hence RA deficiency can seriously impair gut mucosal immunity. Due to its influence on effector T-cell function, vitamin A deficiency can lead to inadequate immune response to some vaccines. Vitamin A supplementation has been shown to lead to 20–30% reduction in all-cause mortality and reduction of incidence and severity diarrhoea diseases and measles [125, 126]. The effect of HIV infection on immune systems mirrors that of malnutrition in most aspects with just a few key differences. Natural killer cell activity and complement activity are increased in HIV infection. There is an increased secretion of pro-inflammatory cytokines (IL-1β, TNF-α, INF-γ and IL-6, IL-8 and soluble IL-2 receptors) and reduction of anti-inflammatory cytokines (IL-1 receptor antagonist, IL-4, IL-10 and IL-13). The chronic inflammatory state is also a hypercatabolic one and leads to increased mobilisation of amino acids from skeletal muscles that are further used for gluconeogenesis in the liver. TNF-α and IFN-γ also suppress appetite leading to decreased food intake. Hypercatabolism and decreased diet lead to malnutrition and HIV wasting. The combination of HIV and malnutrition aggravates reduction of CD4 and CD8 T cells, impairs bactericidal function of neutrophils and macrophages, impairs delayed-type hypersensitivity response and

**42**

Malnutrition depresses all aspects of immune function. HIV infection can lead to wasting and malnutrition by a complex interplay of aetiological factors. This malnutrition compounds immunodeficiency of AIDS and accelerates progression of disease and increases risk of mortality. Addressing nutrition right from the time of HIV diagnosis is a good strategy. Judicious and monitored nutritional therapy can mitigate NIADS and improve HIV clinical outcomes.
