Cachexia in AIDS

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The control of HIV infection remains elusive: during the 1990s, 10-20 million new cases among adults and 5-10 million among children were registered, with an estimated cumulative total of 30-40 million cases of HIV infection in 2005 and more than 10 million of cases of AIDS [7,39] (Fig. 2).

While AIDS is still a fatal disease, new, highly active and more effective therapies have improved patient survival and quality of life. Among these, dietary therapy and palliative care have played an important role [2, 40-42]. Many of the symptoms of AIDS, such as slimming, anorexia, asthaenia, sickness, and nutritional deficits, seem to be reversible if properly treated by administration of proteins, calories, vitamins, minerals, and specific drugs [43-46].

Malnutrition in all its forms is one of the most common and striking phenomena of AIDS [22, 47]. Multiple factors, such as anorexia, sickness, dysgeusia, poor alimentary habits, as well as digestive and absorption disturbances linked to digestive tract infections, cause a progressive weight loss, depletion of lipid stores and lean body mass, and negative nitrogen balance with depletion of circulating and visceral proteins [10, 12, 14-18, 48-53]. The extreme manifestation of this condition is referred to as 'slim disease' [1, 20]. In the 1987 revision of clinical and laboratory criteria defining AIDS, a new condition, wasting syndrome, was included in the list of indicative diseases [9]. HIV wasting syndrome is defined as emaciation and weight loss (predominantly loss of body cell mass) > 10 % of baseline body weight, plus either chronic diarrhoea (at least two loose stools per day for more than 30 days) or chronic weakness and documented fever (for over 30 days) in the absence of concurrent illness.

Since 1988, thousands of AIDS cases have been registered worldwide on the basis of detection of the wasting syndrome, but the real prevalence of cachexia in HIV-positive patients is underestimat

Fig.2. Cumulative HIV infections in the world, 1980-2005

ed, because an associated opportunistic disease (infection or neoplasia) is frequently the greater focus of attention. While cachexia, better than wasting syndrome, defines the severe weight loss that occurs in HIV infection, in the past few years, wasting syndrome has been the third most common indicative condition of AIDS in the USA [54] and the fourth in Italy. Many studies [2,13-18, 23, 40-42,47] have pointed out that, as determined by anthropometric methods, the AIDS-related loss of weight, compared to the usual or ideal weight or to normal population reference percentiles (Fig. 3), is often considerable (30% and more) and is seen in 59-84% of HIV-positive subjects, both hospitalised and out-patients.

Intense anorexia and progressive slimming have a dramatic psychological impact on AIDS patients and their families, and cause a deterioration in the quality of life, an increased susceptibility to infections, and intolerance to drugs [11, 47]. Slimming is due to many factors: the direct cyto-pathic effect of HIV on intestinal cells [55], opportunistic infections [56, 57], cytokines [58, 59], drugs, and neoplasms. There is a reduced intake and assimilation of nutrients, with increased protein-calorie consumption and a condition of cellular hypercatabolism [60], which, if not treated, very quickly leads to death. However, from a macroscopic point of view, weight loss is the most striking event. Terminal cachexia manifests itself clinically, but less evident alterations of the nutritional status must be diagnosed very early on, so that treatment can be administered in time to avoid malnutrition becoming the cause of the disease. For example, such patients exhibit a decrease in body temperature and basal metabolism, which can, however, be high compared with the caloric intake calculated for normal subjects [60]. In addition, there are abnormalities of the skin, muscular and skeletal systems, digestive tract, liver, and respiratory function [24]. Neurological signs may also be present.

Malnutrition also compromises nonspecific factors, including resistance to pathogens and reduced activity of the bone marrow, lymphatic tissues, and reticuloendothelial system. Other, less evident disturbances involve chemical-haemato-logical nutritional parameters, i.e. the development of anaemia and hypoalbuminaemia, reduced plasma titres of vitamins B6 and B12, folic acid,

Fig. 3. Malnutrition in AIDS patients according to three different criteria

selenium, zinc, copper, calcium, and potassium [61-65]. Cell-body mass also progressively decreases (Fig. 4), so that cachexia becomes a disease within a disease and may be included among the various cofactors that have been hypothesised to affect progression of HIV infection to AIDS [66]. In 60% of HIV-positive subjects, PEM is present along with and vitamin and mineral deficits, which together cause progressive physical-metabolic wastage and increased susceptibility to opportunistic infections and drug toxicity. In 80% of deaths due to AIDS, malnutrition is a concurrent cause, and thus must be identified very early by anthropometric and nutritional methods [2, 14-18,26,41,42,66].

The presence or absence of nutritional cofac-tors accelerates or retards the progression of HIV by influencing immune functions. It is well-known that PEM reduces phagocytosis [67-69] and IgA secretion, enhancing bacterial adhesion to respiratory epithelial cells. AIDS is not a food- or drinkborne disease but adequate nutrition may improve the clinical condition of the patient and his or her quality of life. Consequently, evaluation of the nutritional status is a fundamental component of the multidimensional approach to treating HIVpositive patients, both because there is an evident correlation between malnutrition, morbidity, and lethality [70, 71] and because a relatively large number of subjects live in socio-economic conditions that favour the onset of multiple nutritional defects. Study schemes are available that are specific enough to allow definition of the compart-mental composition of the body, visceral protein endowment, and structure of the fat deposits [2]. These schemes can be used to demonstrate that malnutrition presents a mosaic of alterations arising from caloric-protein and food shortage as well as from infections of the gastrointestinal tract. These conditions may be specifically treated.

Among the multiple aetiologies of cachexia (Table 2), the most likely causes of wasting in HIV infection are reduced oral intake, hypermetabo-lism, endocrine abnormalities, especially due to cytokines [34, 72], and futile metabolic cycles of lipids.

Fig.4. Body weight loss and HIV disease progression

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