Predictors and Treatment Strategies of HIV-related Fatigue in the Combined Antiretroviral Therapy Era

Eefje Jong; Lisanne A. Oudhoffc; Cynthia Epskamp; Marlies N. Wagenerd; Miranda van Duijne; Steven Fischerg; Eric C.M. van Gorp


AIDS. 2010;24(10):1387-1405. 

In This Article

Abstract and Introduction


Objective To assess predictors and reported treatment strategies of HIV-related fatigue in the combined antiretroviral (cART) era.
Method Five databases were searched and reference lists of pertinent articles were checked. Studies published since 1996 on predictors or therapy of HIV-related fatigue measured by a validated instrument were selected.
Results A total of 42 studies met the inclusion criteria. The reported HIV-related fatigue prevalence in the selected studies varied from 33 to 88%. The strongest predictors for sociodemographic variables were unemployment and inadequate income. Concerning HIV-associated factors, the use of cART was the strongest predictor. Comorbidity and sleeping difficulties were important factors when assessing physiological influences. Laboratory parameters were not predictive of fatigue. The strongest and most uniform associations were observed between fatigue and psychological factors such as depression and anxiety. Reported therapeutic interventions for HIV-related fatigue include testosterone, psycho-stimulants (dextroamphetamine, methylphenidate hydrochloride, pemoline, modafinil), dehydroepiandrosterone, fluoxetine and cognitive behavioural or relaxation therapy.
Conclusion HIV-related fatigue has a high prevalence and is strongly associated with psychological factors such as depression and anxiety. A validated instrument should be used to measure intensity and consequences of fatigue in HIV-infected individuals. In the case of fatigue, clinicians should not only search for physical mechanisms, but should question depression and anxiety in detail. There is a need for intervention studies comparing the effect of medication (antidepressants, anxiolytics) and behavioural interventions (cognitive-behavioural therapy, relaxation therapy, graded exercise therapy) to direct the best treatment strategy. Treatment of HIV-related fatigue is important in the care for HIV-infected patients and requires a multidisciplinary approach.


The introduction of combined antiretroviral therapy (cART) has resulted in an increase in the overall survival rate of HIV-infected patients. The prevalence of HIV-related and non-HIV-related diseases and symptoms has increased.[1,2] One of the most prevalent and troubling symptoms of HIV is fatigue.[1] The prevalence of fatigue ranges from approximately 20 to 60% in patients with chronic HIV infection[3–5] up to 85% in patients with AIDS.[6,7] Fatigue is defined as a lessened capacity for work and reduced efficiency of accomplishment, usually accompanied by a feeling of tiredness that is not relieved by a good night's sleep.[8]

Fatigue has important social, psychological and behavioural consequences. People with an increased fatigue level have less energy and inclination to work and for social activities, reduced motivation, difficulty concentrating and increased drowsiness. Fatigue may eventually result in unemployment, social isolation, reduced self-care activities and a lessened response to treatment and medical care. It is also associated with an impaired quality of life and is a precursor to lower survival.[5,9,10] The importance of fatigue, and its impact on a patient's life, has been increasingly recognized and studied for a number of chronic diseases, including multiple sclerosis, systemic lupus erythematodes (SLE), chronic viral and cholestatic liver disease, rheumatoid arthritis and HIV.[11]

The cause of fatigue in HIV-infected patients is probably multifactorial. According to current literature, fatigue can be associated with several disease-related factors such as the stage of the disease, the use of cART and certain laboratory parameters, as well as with sociodemographic and psychological factors. Most studies focused on a selection of physiological and/or psychological factors.

HIV-related fatigue and its clinical, social and psychological impact are challenging for the caregiver. To improve the care for HIV-infected patients, a thorough understanding of the complex interplay between sociodemographic, physiological and psychological factors in HIV-related fatigue and available treatment options for HIV-related fatigue is important. We conducted the following narrative review to summarize the latest evidence regarding predictors and treatment strategies for HIV-related fatigue in the cART era.


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