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Clinical, laboratory, and neuroimaging characteristics of fatigue in HIV-infected individuals

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Abstract

Fatigue is among the most common symptoms reported by HIV-infected individuals. Previous reports suggest that the prevalence of fatigue varies by disease status with rates close to 80% in patients with AIDS. However, most studies have not been conducted in the setting of a controlled trial and have not assessed the association of fatigue with cellular markers of brain activity. Data for this study were derived from baseline and longitudinal evaluations in ACTG A5090, a randomized, double-blind, placebo-controlled trial of the Selegiline Transdermal System for the treatment of HIV-associated cognitive impairment. Fatigue was assessed using the Fatigue Severity Scale with scores of >4 considered “fatigued”. Participants in a substudy underwent brain magnetic resonance spectroscopy (MRS) imaging, an in vivo method for assessing brain metabolites associated with neuronal and glia activity. Differences between fatigued and non-fatigued participants were evaluated with respect to demographics and clinical characteristics, plasma and CSF HIV-1 RNA concentration, CD4 counts, and brain metabolites. One hundred and twenty-eight participants were enrolled (88% male, median age = 45 years) and 82 participants (64%, 95% confidence interval 55%, 72%) were fatigued at baseline. MRS was conducted in 62 of the 128 participants. Fatigued participants were significantly younger (p = 0.011), had lower Karnofsky scores (p = 0.032), and had higher levels of depressive symptoms on the Center for Epidemiologic Studies Depression (CES-D) scale (p < 0.001) than non-fatigued participants. Statistically significant differences between fatigued and non-fatigued groups were not detected for plasma and CSF HIV-1RNA concentration, CD4 counts, or on neuropsychological tests. MRS revealed significantly lower levels of the cellular energy marker total creatine (p = 0.002) in the basal ganglia of fatigued participants. Statistically significant differences in other brain metabolites were not detected. Longitudinal data showed that fatigue persisted and worse fatigue at baseline was predictor of future fatigue. Among the cognitive tests, baseline Stroop score was associated with future fatigue. Fatigue was present in 64% of A5090 study participants and persisted during the 24 weeks of follow-up. Fatigue was associated with worse functional performance and depressive mood. Lower cellular energy levels in the basal ganglia, as measured by MRS total creatine concentration, suggest energy dysmetabolism in this brain region. This observation, taken together with the association between fatigue and neuropsychological tests of frontal lobe performance is consistent with the hypothesis of a striatal–cortical circuitry involvement in the symptoms of fatigue.

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Acknowledgements

The study was supported by the AIDS Clinical Trials Group funded by the National Institute of Allergy and Infectious Diseases grants AI38858, AI68636, AI68634, AI069465, AI-069511-02, AI 069434, AI 69432, AI27660, the Neurologic AIDS Research Consortium funded by the National Institute of Neurologic Diseases and Stroke, NS32228, the General Clinical Research Center Units funded by the National Center for Research Resources grants RR025005, 5-MO1 RR00044, UO1-AI 032783-14, and by the National Institute of Mental Health MH64409.

From University of California, San Diego: R. Ellis; K. Nuffer, S. Cahill;

Johns Hopkins University: N. Sacktor; D. Burgess, K. Carter;

University of Rochester: M. Shoemaker, A. Weisbeck; University of Hawaii: V. Valcour; L. Chang; N. Hanks, M. Watters;

UCLA CARE Center: E. Singer, E. Miller; S. Chafey;

University of Washington, Seattle: C. Marra; S. Dunaway, M. Perrin;

University of Pennsylvania, Philadelphia: D. Kolson;

Harvard/Massachusetts General Hospital: N. Venna; T. Flynn;

Washington University, St. Louis: T. Spitz, M. Gould;

Northwestern University: B. Cohen, L. Reisberg;

University of Texas, Southwestern Med Ctr: R. Diaz-Arrastia, C. Lohner;

Columbia University: K. Marder, R. Clouse;

Mount Sinai Medical Center; Beth Israel Medical Center: D. Simpson; D. Mildvan, J. Bailey;

Miriam Hospital: K. Tashima, H. Sousa;

University of North Carolina: D. Currin, S. Pedersen.

Disclosure

The authors report no conflicts of interest.

Statistical analyses conducted by Lijuan Deng, Tzu-min Yeh, and Scott R. Evans.

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Authors and Affiliations

  1. University of Rochester, Rochester, NY, USA

    Giovanni Schifitto & Jianhui Zhong

  2. Harvard School of Public Health, Boston, MA, USA

    Lijuan Deng, Tzu-min Yeh & Scott R. Evans

  3. John A Burns School of Medicine, University of Hawaii, Honolulu, HI, USA

    Thomas Ernst

  4. Washington University School of Medicine, St. Louis, MO, USA

    David Clifford

  5. 1351 Mount Hope Avenue Suite 223, Rochester, NY, 14620, USA

    Giovanni Schifitto

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  1. Giovanni Schifitto
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  2. Lijuan Deng
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  3. Tzu-min Yeh
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  6. Jianhui Zhong
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Correspondence to Giovanni Schifitto.

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Schifitto, G., Deng, L., Yeh, Tm. et al. Clinical, laboratory, and neuroimaging characteristics of fatigue in HIV-infected individuals. J. Neurovirol. 17, 17–25 (2011). https://doi.org/10.1007/s13365-010-0010-5

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  • DOI: https://doi.org/10.1007/s13365-010-0010-5

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