SLEEP ELECTROENCEPHALOGRAM DELTA-FREQUENCY AMPLITUDE, NIGHT PLASMA-LEVELS OF TUMOR-NECROSIS-FACTOR-ALPHA, AND HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

We tested the hypothesis that increases in tumor necrosis factor alpha (TNF-alpha) induced by human immunodeficiency virus (HIV) are associa ted with the increases in slow-wave sleep seen in early HIV infection and the decrease with sleep fragmentation seen in advanced HIV infecti on, Nocturnal sleep disturbances and associated fatigue contribute to the disability of MV infection, TNF-alpha causes fatigue in clinical u se and promotes slow-wave sleep in animal models, With slow progress t oward a vaccine and weak effects from current therapies, efforts are d irected toward extending productive life of HIV-infected individuals a nd shortening the duration of disability in terminal illness, We descr ibe previously unrecognized nocturnal cyclic variations in plasma leve ls of TNF-alpha in all subjects, In 6 of 10 subjects (1 control subjec t, 3 HIV-seropositive patients with CD4(+) cell number > 400 cells per mu l, and 2 HIV-positive patients with CD4(+) cell number < 400 cells per mu l), these fluctuations in TNF-alpha were coupled to the known rhythm of electroencephalogram delta amplitude (square root of power) during sleep. This coupling was not present in 3 HIV-positive subjects with CD4(+) cell number < 400 cells per pi and 1 control subject, In 5 HIV subjects with abnormally low CD4(+) cell counts (< 400 cells per mu l), the number of days since seroconversion correlated significant ly with low correlation between TNF-alpha and delta amplitude, We conc lude that a previously unrecognized normal, physiological coupling exi sts between TNF-alpha and delta amplitude during sleep and that the le ssened likelihood of this coupling in progressive HIV infection may be important in understanding fatigue-related symptoms and disabilities.