Overview
A common problem among HIV-infected people is the HIV wasting syndrome, defined as unintended and progressive weight loss often accompanied by weakness, fever, nutritional deficiencies and diarrhea. The syndrome, also known as cachexia, can diminish the quality of life, exacerbate illness and increase the risk of death for people with HIV.
Involuntary weight loss, or wasting, is one of the most common manifestations of HIV infection. It can occur at any stage of infection and is indicative of disease progression. Chronic unintended weight loss is associated with malnutrition, which may contribute to increased immune suppression including reduction of T-lymphocyte helper and suppressor cells, altered phagocytic functions, and decreased killer-cell activity. Weight loss can result from reduced food intake, altered metabolism, or malabsorption and associated diarihea.Metabolic abnorinalities (hypogonadidism), gastrointesitinal disorders, ciculating growth factors (i.e., proinflammatory cytokines such as IL-1, IL-6, and TNF), and indadequate food intake have all been cited in various reports as potential causes of moderate to severe wasting.
Wasting can occur as a result of HIV infection itself but also is commonly associated with HIV-related opportunistic infections and cancers. HIV wasting syndrome is diagnosed in HIV-infected people who have unintentionally lost more than 10 percent of their body weight. Most patients with advanced HIV disease and AIDS eventually experience some degree of wasting.
The National Institute of Allergy and Infectious Diseases (NIAID) supports basic and clinical research aimed at better understanding and improving treatments for this debilitating condition. Several studies of therapies and nutrition for HIV wasting are being conducted in NIAIDs AIDS clinical trials research network. The AIDS Clinical Trials Group (ACTG), one component of this network, has established the Wasting Pathogen Study Group. Monthly, this group of preclinical and clinical investigators discusses research ideas and priorities as well as ongoing and planned clinical trials.
Many approaches have been used to reverse weight loss in HIV-infected people, including appetite stimulants, anabolic agents, cytokine inhibitors and hormones. Goals of therapy include both increase in body weight and increase in lean body mass (muscle).
Currently, the precise causes of the HIV wasting syndrome are not well known, and probably vary among individuals. However, a growing body of evidence suggests that many factors may contribute to wasting including inadequate dietary intake, malabsorption of nutrients, abnormalities in metabolism and energy expenditure, and HIV-related infections.
Reduced caloric intake among HIV-infected people is often the result of a loss of appetite, frequently because of nausea. A number of agents to enhance dietary intake have been evaluated in NIAID clinical trials; two of them -- megestrol acetate (megace) and dronabinol (marinol, which contains the active ingredient of marijuana, THC) -- are currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV wasting syndrome. Nutritional supplements also have a role in boosting caloric intake and currently are being assessed in NIAID's clinical trials research network.
Many HIV-infected people suffer from aphthous ulcers of the mouth or esophagus that make eating difficult. A recent NIAID-supported study demonstrated that the drug thalidomide can safely and effectively heal these ulcers. This finding promises to remove a major impediment to adequate nutrition for HIV-infected people who suffer from these painful sores.
Despite ingesting sufficient calories, many people with HIV lose nutrients because of diarrhea, vomiting or malabsorption of nutrients in their intestines. Malabsorption may be caused by HIV itself as well as by enteric infections associated with HIV disease. Research into HIV's effects on the gastrointestinal tract and into diseases such as cryptosporidiosis and microsporidiosis may help explain the causes of HIV-associated diarrhea and wasting.
Increased calorie usage, and in some cases the breakdown of muscle and other tissues, also contributes to HIV wasting. Agents that reverse metabolic abnormalities, such as testosterone and growth hormones, have been studied by NIAID-supported investigators and others. One such drug, a growth factor known as somatropin (Serostim), was approved by the FDA in 1996 for the treatment of HIV-associated wasting. Researchers also have found that increased levels of immune-signalling molecules (cytokines) such as interleukin-6 and tumor necrosis factor-alpha (TNF-alpha) are associated with HIV wasting. Drugs that block TNF-alpha may have a role in the treatment of this condition.
Source:
NIAID (National Institute of Allergy and Infectious
Diseases)
National Institutes of Health,
Bethesda, MD 20892
May 1997
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