October 23, 2012
The research team states that "fatigue remains a very common and often severe symptom in [HIV-positive] patients." Furthermore, they note that "it is likely that this condition is significantly under-recognized."
The researchers were surprised at the high level of fatigue reported by participants because most had viral loads in their blood of 40 copies/ml or less. Moreover, their CD4+ counts were relatively high at about 520 cells. In the time before the widespread availability of ART, high viral loads and low CD4+ cell counts were associated with severe fatigue.
The underlying cause(s) of fatigue in some ART users in the modern era is likely complex and could involve biological and psychological factors. However, none of the HIV-positive participants had untreated depression or anxiety (although the research team cannot fully exclude that some patients may have had undiagnosed depression). What might the possible biological factors be? Some clues have emerged from the present study. The researchers found that many HIV-positive participants with severe fatigue tended to have the following features:
The research team was unable to assess which of these three factors had the most important bearing on fatigue because all three factors were so commonly seen together among people with fatigue.
The d-drugs are now known to damage structures called mitochondria -- the energy-producing parts of a cell, particularly in nerves. One d-drug, d4T, has been linked to the development of the lipodystrophy syndrome. It is therefore possible that past exposure to d-drugs may have damaged nerves and muscles, predisposing some HIV-positive people to fatigue. Certainly, in the case of HIV-negative people with CFS, other researchers using magnetic resonance imaging (MRI) have found that muscle cells may have damaged mitochondria.
Another important new finding from the UK study was the link between fatigue and symptoms suggestive of dysfunction within the autonomic nervous system.
Emerging research suggests that dysfunction within the autonomic nervous system plays an important role in perhaps inciting and intensifying fatigue in several chronic diseases, such as the following:
In an exciting development, the UK's Medical Research Council has recently funded several research projects to explore autonomic nervous system dysfunction and fatigue in CFS. This research may in the future help researchers better understand fatigue in other chronic conditions, including HIV (Brendan Payne, M.D., personal communication).
The cross-sectional nature of the present study means that its findings are not definitive. Cross-sectional studies are cheaper and less cumbersome than larger studies that run for several years. The present study did have several strengths, including its size and the fact that there were three different groups that could be compared against each other. Moreover, the research team should be praised for initiating an investigation into a subject that is difficult to study, such as fatigue.
Lead researcher Brendan Payne, M.D., suggests that physicians and nurses "actively look for fatigue in their HIV-positive patients." Dr. Payne also suggests an integrated approach to managing this fatigue, similar to what has been proposed for patients with primary biliary cirrhosis. As part of such an approach, doctors would first perform investigations to rule out common causes of fatigue. In HIV infection this would likely include assessments for anemia, diabetes, dysfunction of the thyroid gland, depression, less-than-normal levels of testosterone, co-infections, deficiencies of vitamin B12 and other nutrients, sleep disturbances and so on.
In clinical trials of the treatment of HIV-related fatigue, researchers in the U.S. have found that the drug modafinil (Provigil) and its analogues (armodafinil, Nuvigil) can sometimes provide relief.
We thank infectious disease specialist Brendan Payne, M.D., for his research assistance, helpful discussion and expert review.
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