**4. Malnutrition and the immune system**

The relationship between malnutrition and HIV in children is complex. These two conditions interact and can create a vicious circle of poor health outcomes. Moreover, multiple studies have documented the positive effect of appropriate


#### **Table 1.**

*Relevant baseline metabolic profile of HIV-infected and HIV-negative patients. Bold values denote statistical significance at the p<0.05 level.*

nutrition of vitamins and antioxidants, cofactors of metabolic pathways, in enhancing and potentiating the immune system. On the other hand, malnutrition has also been implicated in impairing immunity, which could even lead to an immunodeficiency status with degraded lymphoid tissue containing lower concentrations of CD4 cells, target of HIV [5, 15]. In such a weak or deficient immune system, the ability to combat infections is reduced. Consequently, malnutrition can speed up the progression of the HIV/AIDS disease by creating a favorable environment, which contributes to the oxidative stress, which accelerates the death of the immune cells and increase viral replication. Stressing the necessity of vitamin A and iron, some authors associated their deficiencies with higher mortality risk among HIV/AIDS

**21**

*HIV-Infected Children and Nutrition: The Friend and The Foe*

patients [19]. In fact, HIV-infected patients have, in general, an enhanced activity of proinflammatory cytokines (TNF-α, IL-1, IL-6, and others), which can cause in children among other side effects retarded growth and a loss in body weight. At the same time, such immune-compromised children will acquire opportunistic infections, which will decrease by themselves the intake of food, thus leading to the aggravation of the immunodeficiency state and the higher incidence of several overlapping infections, such as tuberculosis, oral and esophageal candidiasis, pneumonia, skin infections, and persistent diarrhea. All these complications will negatively affect the nutritional status. In addition, anemia, which is a possible consequence of malnutrition, is also a complication of HIV infection that can cause growth retardation in children [2, 15, 20]. These children often require highly aggressive management protocols including intensive antimicrobial administrations and the provision of a wellbalanced nutritional, higher caloric diet [20, 21]. The cooccurrence of tuberculosis adds another complication related to the decrease in the sensitivity of tuberculin skin test (TST), which is used as an indicator for management. This issue is aggravated further in immune-compromised children from HIV and severe malnutrition; there is a block of the immune reaction, type IV hypersensitivity, needed for a reactive TST, consequently affecting the appropriate management protocol [20, 21].

In addition, it was documented that the energy needs increase in HIV-infected children compared to normal children by almost 10% in the early stage of the disease. However, such an increased demand will go up to 20–30% in symptomatic HIV with opportunistic infections and to 50–100% in case of severe malnutrition. These data are based on studies in HIV-infected adults or in non-HIV-infected children and, therefore, have a low level of evidence [2]. A major finding of these studies is that HIVinfected children with SAM present with significant reductions in the adipocytokines, leptin, and adiponectin that are associated with mortality during inpatient hospitalization. In addition, HIV-infected and HIV-negative patients presented with similar degrees of wasting and edema, who achieved similar rates of growth and recovery [22]. Accordingly, as evidenced in **Table 1**, a baseline metabolic profile including amino acid

levels was suggested for HIV-infected and HIV-negative patients [22].

The introduction of therapeutic nutrition support and appropriate fluid rehydration has improved the rehabilitation process, shortened hospital stays of HIV-uninfected severely malnourished children, and addressed micronutrient and macronutrient deficiencies [19]. In the stabilization phase, F-75 is given as a therapeutic food. It is a low-protein milk-based formula diet. It is followed gradually by F-100 over a couple of days. The transitional phase until rehabilitation phase is reached. F-100 is a milk formula with higher protein and energy content than F75. However, the ready-to-use therapeutic food (RUTF) has replaced the F-100, especially in cases of severe acute malnutrition. In general, RUTF are pastes, no liquids, containing a combination of milk powder, electrolytes, and micronutrients. They provide the child with the same nutrients as F-100 plus iron [3, 4, 7]. As for rehydration, ReSoMal is commonly used. It contains approximately 45 mmol Na, 40 mmol K, and 3 mmol Mg per liter [19]. However, the metabolic and nutrient needs of HIV-infected children, in whom persistent anorexia is frequent, should be more clearly defined. In case of severe diarrhea often associated with high mortality rates, the provision of suitable feeding protocols is highly recommended. In brief, protocols for appropriate nutrition support therapy for severely malnourished infants below age 6 months are needed [23].

Although wasting can be treated in HIV-uninfected children with nutritional therapy alone, effective regimens for HIV-infected children need to be developed.

**5. Nutrition as an adjunct therapy**

*DOI: http://dx.doi.org/10.5772/intechopen.85417*

#### *HIV-Infected Children and Nutrition: The Friend and The Foe DOI: http://dx.doi.org/10.5772/intechopen.85417*

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

• NEFA (mmol/L) 0.65 ± 0.10 0.54 ± 0.06 0.285 • Total ketones (μmol/L) 826 ± 259 424 ± 95 **0.0387**

• C2 (μmol/L) 22.3 ± 3.5 14.4 ± 2.4 0.0103

• Insulin (μIU/ml) 1.81 ± 0.48 2.45 ± 0.45 0.321 • Growth hormone (ng/ml) 12.4 ± 2.7 11.0 ± 1.3 0.380

• Leptin (pg/ml) 69.8 ± 26.6 292 ± 52 **0.0163** • Total adiponectin (ng/ml) 8049 ± 1081 15,268 ± 1133 **0.0017** • HMW adiponectin (ng/ml) 4409 ± 757 9356 ± 761 **0.0014**

• Alanine 153 ± 27.4 217 ± 16.2 **0.0330** • Valine 100 ± 10.7 75.6 ± 6.3 **0.0248** • Phenylalanine 79.6 ± 7.7 43.0 ± 4.5 **0.0067**

• IL-2 (pg/ml) 7.7 ± 2.7 3.6 ± 1.2 **0.0158** • TNF-α (pg/ml) 43.0 ± 5.5 37.4 ± 9.5 **0.0248**

• Glucose (mg/dl) 77.1 ± 7.9 85.9 ± 3.9 0.474 • Creatinine (mg/dl) 0.30 ± 0.04 0.27 ± 0.03 0.296 • Triglycerides (mg/dl) 177.6 ± 14.0 122.9 ± 12.2 **0.0008**

**Adipocytokines**\* **n = 13 n = 46**

**Fatty acid metabolites**

• Even-chain acylcarnitine molar sum (μmol/L)

**Acylcarnitines**

**Hormones**

**Amino acids**

(μmol/L)

**Other**

**Table 1.**

• Amino acid molar sum

**Inflammatory cytokines**

*\*Excludes patients on ARVs. Adapted from [22].*

*significance at the p<0.05 level.*

**HIV-infected (n = 16) HIV-negative (n = 46) p-Value Mean ± SEM**

24.0 ± 3.7 16.0 ± 2.6 **0.0108**

1230 ± 62 1190 ± 51 0.417

nutrition of vitamins and antioxidants, cofactors of metabolic pathways, in enhancing and potentiating the immune system. On the other hand, malnutrition has also been implicated in impairing immunity, which could even lead to an immunodeficiency status with degraded lymphoid tissue containing lower concentrations of CD4 cells, target of HIV [5, 15]. In such a weak or deficient immune system, the ability to combat infections is reduced. Consequently, malnutrition can speed up the progression of the HIV/AIDS disease by creating a favorable environment, which contributes to the oxidative stress, which accelerates the death of the immune cells and increase viral replication. Stressing the necessity of vitamin A and iron, some authors associated their deficiencies with higher mortality risk among HIV/AIDS

*Relevant baseline metabolic profile of HIV-infected and HIV-negative patients. Bold values denote statistical* 

**20**

patients [19]. In fact, HIV-infected patients have, in general, an enhanced activity of proinflammatory cytokines (TNF-α, IL-1, IL-6, and others), which can cause in children among other side effects retarded growth and a loss in body weight. At the same time, such immune-compromised children will acquire opportunistic infections, which will decrease by themselves the intake of food, thus leading to the aggravation of the immunodeficiency state and the higher incidence of several overlapping infections, such as tuberculosis, oral and esophageal candidiasis, pneumonia, skin infections, and persistent diarrhea. All these complications will negatively affect the nutritional status. In addition, anemia, which is a possible consequence of malnutrition, is also a complication of HIV infection that can cause growth retardation in children [2, 15, 20]. These children often require highly aggressive management protocols including intensive antimicrobial administrations and the provision of a wellbalanced nutritional, higher caloric diet [20, 21]. The cooccurrence of tuberculosis adds another complication related to the decrease in the sensitivity of tuberculin skin test (TST), which is used as an indicator for management. This issue is aggravated further in immune-compromised children from HIV and severe malnutrition; there is a block of the immune reaction, type IV hypersensitivity, needed for a reactive TST, consequently affecting the appropriate management protocol [20, 21].

In addition, it was documented that the energy needs increase in HIV-infected children compared to normal children by almost 10% in the early stage of the disease. However, such an increased demand will go up to 20–30% in symptomatic HIV with opportunistic infections and to 50–100% in case of severe malnutrition. These data are based on studies in HIV-infected adults or in non-HIV-infected children and, therefore, have a low level of evidence [2]. A major finding of these studies is that HIVinfected children with SAM present with significant reductions in the adipocytokines, leptin, and adiponectin that are associated with mortality during inpatient hospitalization. In addition, HIV-infected and HIV-negative patients presented with similar degrees of wasting and edema, who achieved similar rates of growth and recovery [22]. Accordingly, as evidenced in **Table 1**, a baseline metabolic profile including amino acid levels was suggested for HIV-infected and HIV-negative patients [22].
