Background:  Fatigue is among the most common symptoms reported by HIV-infected individuals. Reports suggest that the prevalence of fatigue varies by disease status with rates near 80% in patients with AIDS. 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.

Methods:  Data for this study were derived from baseline evaluations in AIDS Clinical Trials Group (ACTG) A5090, a randomized, double-blind, placebo-controlled trial of the selegiline transdermal system (STS) for the treatment of HIV-associated cognitive impairment. Fatigue was assessed using the fatigue severity scale (FSS) with scores of >4 considered “fatigued”; 44 participants 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 cerebrospinal fluid (CSF) HIV-1 RNA concentration, CD4 counts, and brain metabolites using Kruskal-Wallis, exact, or score tests for continuous, nominal, and ordinal factors, respectively.

Results:  We enrolled 128 participants (88% male, 51% white, median age 45, median CD4 425, and 55% with HIV-1 RNA ≤50 copies/mL); 82 participants (64%, 95%confidence interval 55%, 72%) were “fatigued” at baseline. Fatigued participants were significantly younger (p = 0.01), had lower Karnofsky scores (p = 0.015), and had higher levels of depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D) (p <0.001), than non-fatigued participants. Statistically significant differences between fatigued and non-fatigued groups were not detected for plasma and CSF HIV-1 RNA concentration, CD4 counts or on neuropsychological tests. MRS revealed significantly lower levels of the cellular energy marker creatine (p = 0.002) in the basal ganglia of fatigued participants. Statistically significant differences in other brain metabolites were not detected.

Conclusions:  Fatigue was present in 64% of A5090 study participants, a rate similar to previous reports. Younger participants were more likely to display fatigue symptoms, possibly reflecting higher functional expectations. Lower cellular energy levels in the basal ganglia, as measured by MRS creatine concentration, suggest that energy dysmetabolism in this brain region may play a role in the central mechanisms of fatigue.