Any other possible causes to be aware of?
Yes. In recent years, a significant amount of research has focused on metabolic problems that can cause wasting. Metabolism – an intricate system by which nutrients are either broken down (catabolism) for energy purposes or stored (anabolism) for later use – has been shown to become highly irregular in people with HIV.
More simply, metabolism is the way in which the body converts food into energy. To fuel its energy needs, the body first breaks down glucose and lipids circulating in the blood. Once these are used up, the body goes after stored energy: either fat or protein in muscle.
In HIV-negative people, fat is burned and protein is spared. In HIV-positive people, sometimes protein is burned and fat is spared. We know this because people with HIV often have elevated glucose levels and fat levels (hyperlipidemia) in their blood and, especially during an OI, have a negative nitrogen balance (a marker of muscle loss).
Why this occurs in HIV-infected people is not well understood. While a number of studies have demonstrated a strong connection between the severity of immune-system damage and the likelihood of developing wasting, it is still not clear whether or not immune system damage is an underlying cause of wasting.
In its response to HIV and OIs, an abundance of hormone-like substances called cytokines are produced by cells to more effectively communicate with each other. While these cytokines play an important role in bolstering the immune response against an infection, they may be too much of a good thing in people with weight loss and wasting. The cytokines interleukin-1 (IL-1), interferons (alpha, beta, and gamma), and tumor necrosis factor (TNF) have all been shown to cause the classic symptoms experienced during an illness. These include some that are prominent in HIV disease: fever, nausea, decreased appetite, fatigue, diarrhea, anemia, and confusion. Still it is not entirely clear whether or not hyperactivity of the immune system directly causes wasting or, more specifically, muscle loss.
Numerous studies have said that hormones may play a role in weight loss and wasting. Many people with HIV experience significant hormonal (endocrine) problems such as decreased production of both insulin-like growth factor (a precursor of growth hormone) and testosterone. Anabolic hormones such as these play a large role in turning protein into muscle. Decreased testosterone production (hypogonadism) is a common problem in HIV-infected people. Rates vary from 25% to 45%, depending on the stage of HIV disease (e.g., T-cell count). Possible causes of hypogonadism include:
- Infections of the testicles (including HIV)
- Drug side effects (particularly from ketoconazole, ganciclovir, and megestrol acetate)
- Elevations in cortisol levels (a hormone produced by the adrenal glands)
No matter what the cause, low testosterone levels have been shown to play a major role in the development of fatigue, depression, decreased sex drive, and weight and muscle loss.
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