Unravelling the Complexity of HIV and Fatigue

October 23, 2012

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In the time before potent combination therapy for HIV (commonly called ART or HAART) became available one of the symptoms associated with HIV infection was persistent fatigue. In some cases, the intensity of fatigue was severe and could be disabling. This symptom was generally not linked to depression or other obvious health problems. Moreover, the reason for this fatigue was not clear but it was linked to declining CD4+ cell counts and worsening health.

It is uncertain how common HIV-related fatigue is in the modern era. Given the tremendous benefit of ART on overall health and survival, some researchers expect that HIV-related fatigue may now be less common. A team of researchers at the Royal Victoria Hospital in Newcastle-upon-Tyne in the UK have been studying fatigue in people with HIV infection and in HIV-negative people with Chronic Fatigue Syndrome (CFS) and comparing them to otherwise-healthy HIV-negative people.

The findings from their investigation with 240 participants suggest that, in the present era, fatigue is relatively common and can be severe in HIV-positive people. It appears likely that previous exposure to certain medicines may have played a role in the fatigue seen in some HIV-positive people. This exposure may have caused lasting dysfunction within part of the nervous system called the autonomic nervous system, which, in turn, led to fatigue.

Study Details


Researchers recruited three groups of people as follows:

  • 100 HIV-positive participants
  • 100 healthy HIV-negative people
  • 76 HIV-negative people who had been diagnosed with CFS

All participants completed questionnaires that had been previously validated for assessing fatigue and dysfunction of the autonomic nervous system. Also, data collected from the HIV-positive participants' medical records was used for analysis.

The average profile of the HIV-positive participants was as follows:

  • 64% men, 36% women
  • age: 47 years
  • duration of HIV infection: 8 years
  • current CD4+ cell count: 520 cells
  • lowest-ever CD4+ count: 194 cells
  • 91% were currently taking ART
  • 78% of all participants had an HIV viral load of 40 copies/ml or less
  • 1% of participants were co-infected with hepatitis C virus (HCV)

Results -- Fatigue

Slightly more than half of the HIV-positive participants (51%) reported an excessive degree of fatigue. Moreover, 28% of HIV-positive people reported a severe degree of fatigue.

The intensity of fatigue experienced by HIV-positive participants was significant and at least threefold greater than that reported by healthy HIV-negative people.

HIV-positive people who reported the greatest intensity of fatigue had a level similar to that reported by participants with CFS.

Running on Automatic

The part of the nervous system that deals with functions that can occur without conscious involvement is called the autonomic nervous system. There are many functions under the influence of the autonomic nervous system, including the following:

  • blood pressure
  • breathing
  • heartbeat
  • control of muscles such as those that are part of the anus and bladder
  • sleeping
  • temperature control

One consequence of a dysfunctional autonomic nervous system can be orthostatic hypotension (OH). In OH, the following symptoms can occur:

  • dizziness upon standing
  • blurred vision
  • reduced sense of hearing
  • difficulty concentrating
  • weakness

These symptoms can have other causes, including drug side effects, so having them does not necessarily mean that a person has underlying problems with their autonomic nervous system.

HIV and a Dysfunctional Autonomic Nervous System

Symptoms suggestive of dysfunction within the autonomic nervous system were common among HIV-positive participants, with 38% reporting them. Furthermore, HIV-positive participants tended to report more severe symptoms compared to healthy HIV-negative participants.

Among HIV-positive participants, fatigue was statistically linked to the following factors -- having symptoms suggestive of autonomic nervous system dysfunction and exposure to so-called "d-drugs" such as the following:

  • d4T (stavudine, Zerit)
  • ddI (didanosine, Videx)
  • ddC (zalcitabine, Hivid)
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This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication CATIE News. Visit CATIE's Web site to find out more about their activities, publications and services.

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