14.2.1. The link between HIV and nutrition

Adverse nutritional outcomes, such as abnormalities in growth and metabolism, are common in children infected with HIV and can be major contributors to both morbidity and mortality. The association between HIV infection and low weight-for-age or growth faltering in HIV-infected children has been reported in both resource-rich and resource-poor settings. In adults, the nutritional consequences of HIV were also among the first to be recognized and reported.

These interactions have particular relevance for children living with HIV because of the significant geographical overlap between regions with a high HIV prevalence and areas where food insecurity and moderate and severe malnutrition are common. In HIV-uninfected children, the relationship between protein-energy malnutrition, micronutrient deficiency and adverse effects on the immune system has been recognized for many years [176]. The ability of HIV to cause profound anorexia and wasting further complicates the situation, especially where resources are not available to thoroughly investigate children to determine whether the primary cause of wasting is HIV infection or food insufficiency or other infections.

14.2.2. The relationship between poor growth and survival of children living with HIV

Poor growth in HIV-infected children may have many causes. Poor growth can be attributed to reduced food intake due to socioeconomic circumstances or altered care-giving practices such as when the mother herself is unwell. OIs and their effect on food intake, absorption and metabolism can cause weight loss, which is sometimes very rapid. However, even when children are otherwise asymptomatic, HIV infection and the metabolic disturbances that it can induce may result in poor linear growth and weight gain [177].

The poor nutritional status of children living with HIV, including those children who have already started ART, is closely associated with their likelihood of dying. HIV-infected children who are significantly underweight are much more likely to die than HIV-infected children who are not malnourished. [178] Similar findings have been described in adults living with HIV, including adults receiving ART.

Given the important relationship between HIV, nutrition, growth and survival of children living with HIV, WHO recommends that nutritional assessment and support be an integral part of the care plan of an HIV-infected infant or child, irrespective of whether the child is on ART (WHO 2009). For further information on poor growth and detailed definitions of growth parameters and appropriate nutritional interventions, reference should be made to the WHO Guidelines for an integrated approach to nutritional care of HIV-infected children (6 months – 14 years) [140].

14.2.3. The energy and protein needs of children living with HIV

HIV and associated OIs increase nutritional needs. This is compounded by the decreased appetite and food intake that frequently occurs during any febrile illness or infection. Loss of weight and especially loss of lean body mass are associated with HIV disease progression and decreased survival. The following points are recognized:

• During symptomatic HIV or episodes of OI, energy requirement increases by 20 – 30% [140, 173-175]. Identification and prompt treatment of OIs causing growth failure, in addition to nutrition counselling and support, may prevent further decline in nutritional status. In particular, diarrhoeal illnesses and TB can result in significant weight loss. Nutrition support for HIV-infected children with prolonged diarrhoea has been shown to result in significant and sustained weight gain. [179]
• During and following periods of severe malnutrition, energy requirements may increase by 50 – 100% in order to recover weight [140, 173-175]. Evidence from children who are severely malnourished and who are not HIV infected indicates that energy intake needs to increase by 50 – 100% in order for children to recover lean body mass and achieve normal weight-for-age. There are no data specific for severely malnourished HIV-infected children but it is likely that they will have the same energy and protein needs as severely malnourished HIV-uninfected children. Studies from Malawi suggest that the WHO-recommended management of children with severe malnutrition can be effective in HIV-infected children. Ready-to-use therapeutic feeds (RUTF) appear to be equally effective in severely malnourished HIV-infected children as in severely malnourished HIV-uninfected children. However, there are few data available to specifically address this question. In particular, there is little knowledge about the energy requirements of HIV-infected children who have been started on ART and who are recovering from severe malnutrition.
• During asymptomatic HIV infection, energy requirements in adults increase by 10% to maintain body weight. There is currently inconclusive evidence to support this in children. Resting energy expenditure (REE) has been found to be 10% higher in asymptomatic HIV-infected adults [180]. This has been a consistent finding in energy balance studies conducted among adults in North America and Europe. The increase in REE has been correlated with HIV viral load and is potentially reversed with effective viral suppression during ART [181]. Few comparable studies have been conducted in HIV-infected children and results from these studies are not conclusive [177, 182, 183].

However, in a meta-analysis of macronutrient interventions in HIV-infected, asymptomatic, well-nourished adults, balanced nutritional supplementation providing 600 - 960 kcal/day improved energy and protein intake, but was found to have no effect on body weight, fat mass, fat-free mass or CD4 count [184]. In non-malnourished HIV-infected children, current evidence does not support increased energy intake, either through increased food intake or macronutrient supplements. Data are insufficient to support an increase in protein intake above normal requirements for health (i.e. 12 – 15% of total energy intake) [173-175]. Further research is needed in children and situations where malnutrition is common.

14.2.4. The micronutrient needs of children living with HIV

Micronutrient deficiencies are common in HIV-infected adults and children, particularly in developing countries where diets are often inadequate. HIV is known to impact on nutrient intake, absorption, metabolism and storage. Micronutrient deficiency and HIV both impact on immune function and for this reason there has been much interest in micronutrient supplementation and its possible role in improving immune function and HIV disease progression. Micronutrient supplementation has been shown to correct deficiency in malnourished HIV-infected individuals but it is unclear how much this contributes to restoration of immune function. Some studies have investigated the use of very high doses of different micronutrients, more than required to simply replenish nutrient stores. However, micronutrient supplementation above 1 RDA may have harmful effects and so caution is required. The following points are recognized:

• Micronutrient supplementation does not appear to have any effect on HIV progression, mortality or morbidity. In a meta-analysis examining the effect of vitamin A or multiple micronutrient supplementation trials in HIV-infected adults and children, there was no conclusive evidence that these reduced morbidity, mortality or AIDS-defining infections, or improved CD4 counts [185]. Trials of very high-dose (up to 22 × RDA) micronutrient supplementation in adults and pregnant women have shown some effect on markers of HIV progression, but the efficacy and safety of such approaches in children has not been evaluated [185, 186].
• High-dose vitamin A supplementation in children, as given to their uninfected peers, has been shown to reduce all-cause mortality and diarrhoeal morbidity. In several studies conducted in Africa, vitamin A supplements were found to improve health outcomes in HIV-infected children including growth reduced diarrhoeal morbidity and all-cause mortality [187-190]. Vitamin A supplements should be given in accordance with the WHO IMCI recommendations, as well as the prevention schedule for children at high risk for vitamin A deficiency [170, 191]. Current evidence indicates that zinc is a useful adjunct to oral rehydration therapy for all children with diarrhoea. Zinc has been found to be safe when given to HIV-infected children in similar doses as for HIV-uninfected children [192]. In one study, it was found to reduce diarrhoeal prevalence and severity while in another it was not found to have any effect on recovery from diarrhoea in HIV-infected children [193, 194]. The WHO recommends zinc supplementation for acute diarrhoea in children and HIV-infected children should be managed in the same way as their uninfected peers [140]. There are insufficient data on the effect of other micronutrients in HIV-infected children to draw any conclusion and so HIV-infected children should be managed in the same way as other children with clinical evidence of micronutrient deficiency.

14.3.1. Nutritional assessment

Nutritional assessment, i.e. the systematic evaluation of nutritional status, diet (including caregiving practices and family food security) and nutrition-related symptoms, is essential for the early identification of malnutrition and growth faltering. Growth monitoring can also contribute to monitoring HIV disease progression and treatment efficacy of children on ART.

For these reasons, HIV-infected infants and children should initially undergo a complete nutritional assessment and thereafter be weighed and have height measured and recorded at each scheduled visit and more often if weight gain is inadequate. Weight and height gain should be evaluated with reference to the WHO or national reference growth curves [195]. If growth faltering is identified, then further assessment should be made to determine the cause, and plan appropriate clinical responses with appropriate nutritional counselling and referral as needed. The Guidelines for an integrated approach to the nutritional care of HIV-infected children (6 months – 14 years) provide details of appropriate nutritional interventions [140]. Growth monitoring should be integrated into the assessment of ART response.

In children who are responding well to ART, nutritional assessment and counselling should include information on healthy eating and avoidance of obesity. Further research is needed to assess the rates and determinants of lipodystrophy in children on ART. There is currently insufficient evidence on the effect of nutrition on the development and potential for amelioration of lipodystrophy and its long-term cardiovascular effects.

14.3.2. Meeting the energy needs of children living with HIV

At clinic visits, the nutritional needs of children living with HIV should be assessed and a nutritional care plan agreed upon with the mother or caregiver. The assessment should consider the child's growth pattern, appetite, presence of OIs and any clinical signs of malnutrition.

If children are growing normally, then no additional food is necessary. However, mothers or caregivers should be encouraged to provide a balanced diet and counselled on the nutritional value of different foods and general food hygiene [140].

If a child is found to be growing poorly, then a full dietary assessment is needed in addition to an assessment of drug adherence if the child is on ART [140]. Mothers or caregivers should be asked about food availability and food types offered to the child, as well as who feeds the child, how much and how often. Children should be examined to detect signs of OIs or wasting. Appropriate clinical interventions should be provided. Additional energy can be provided through a combination of increasing the energy density of family foods, increasing the quantity of food consumed each day and providing energy supplements. Mothers or caregivers should be referred to food support programmes, if available. Caregivers should also be counselled on how to manage anorexia, alleviate the symptoms of conditions that interfere with normal ingestion or digestion, such as mouth sores, oral thrush and diarrhoea, and ensure adequate energy intake [140].

In children experiencing growth failure (failure to gain weight, weight loss), feeding difficulties (due to oral thrush, loss of appetite) or malabsorption due to persistent diarrhoea, more targeted support may be necessary. Following acute illnesses when weight loss might have occurred, it is important to prioritize nutritional support and interventions to enable the child to recover nutritionally as well as from the clinical illness. Common illnesses should be managed according to the IMCI guidelines [191]. The Guidelines for an integrated approach to the nutritional care of HIV-infected children (6 months – 14 years) provides details of appropriate nutritional interventions [140].

14.3.3. Meeting the micronutrient needs of children living with HIV

Adequate micronutrient intake is best achieved through a balanced diet [175]. Caregivers should be counselled on optimum local food choices and preparation methods to ensure maximal micronutrient intake through healthy eating, equivalent to 1 RDA [140]. Food support programmes may be beneficial.

In situations where appropriate micronutrient intake cannot be achieved, supplementation may be necessary. Special consideration should be given to the micronutrient intake and status of HIV-infected children experiencing growth failure, OIs or prolonged diarrhoea. HIV-infected children should receive regular vitamin A supplementation and zinc during diarrhoeal illness according to WHO recommendations. Currently, there are inadequate data to inform the optimal formulation of micronutrient supplements for HIV-infected children [175]. The efficacy and safety of very high-dose supplements in immunocompromised and malnourished children needs urgent consideration.

All children suspected of specific micronutrient deficiency should be assessed further. Micronutrient deficiency is difficult to diagnose in patients with chronic or acute infections, due to the interaction between acute-phase response proteins and micronutrient metabolism, storage and sequestration, making serum levels of certain micronutrients misleading [196, 197]. Special care should be taken when evaluating the micronutrient status of HIV-infected children, particularly during episodes of OIs.

14.3.4. Managing the HIV-infected child who has severe malnutrition

Severe wasting is a common clinical presentation of HIV infection in children [172]. All children with severe malnutrition are at risk for a number of life-threatening problems and require urgent and appropriate nutritional rehabilitation. HIV-infected children with severe malnutrition have a higher risk of mortality than uninfected children due to the frequency and severity of OIs including TB. Those who survive the initial rehabilitation period usually recover in a manner similar to uninfected children [198, 199], though they need urgent initiation of ART.

The treatment of severe malnutrition in HIV-infected children is the same as for uninfected children [200]. In uninfected children, the initial period of stabilization of acute complications and cautious refeeding may take 5 – 7 days. In HIV-infected children, this may take longer due to direct effects of HIV on the gut, appetite suppression or presence of OIs that may be hard to diagnose, such as TB. The optimal time at which to start ART in severely malnourished children is not presently known [201]. There are inadequate data on the effectiveness, pharmacokinetics and safety of ARVs in severely malnourished children to accurately inform this decision and further research on these matters is urgently needed. Expert opinion suggests that HIV-infected children with severe malnutrition, according to international or national guidelines, should be stabilized from the acute phase of malnutrition while simultaneously preparing for initiation of ART; ART should be initiated as soon as clinically possible following stabilization [171, 172, 200].

It needs to be emphasized that where malnutrition is endemic, HIV-infected children may become severely malnourished due to a lack of an adequate, balanced diet. In these settings, it is very difficult to differentiate severe malnutrition that is primarily due to HIV infection from other non-HIV causes, including food insecurity and starvation. Children with an unknown HIV status, who present with severe malnutrition in settings where HIV and food insecurity are common, should be tested for HIV and considered for ART.

Immediate initiation of ART is indicated in HIV-infected infants and children with unexplained severe malnutrition that is not caused by an untreated OI, and who do not respond to standard nutritional therapy (i.e. WHO stage 4 disease).

14.3.5. Nutritional considerations for the child who is receiving ART

Successful viral suppression and immune restitution with ART can reverse losses in weight and linear growth. Children who gain weight rapidly with ART and adequate nutrition should be reassessed frequently and ARV dosages revised as needed (see Annex E). The recurrence of growth failure and severe malnutrition that is not due to food insufficiency in children receiving ART may indicate treatment failure, non-adherence to ARVs, or an OI.

Currently available data are insufficient to determine whether ART ameliorates micronutrient deficiencies and further research is required in this field.

Caregivers should be counselled as to potential food interactions with prescribed ART and how to alleviate any drug-related gastrointestinal side-effects. Nutrition counselling and support should aim to enable caregivers to provide a balanced diet that meets energy, protein and micronutrient needs. This should include referral to food programmes and micronutrient supplementation to rectify deficiencies.