Effects of sleep disorders and fatigue on HIV disease progression in older children and adolescents

RATIONALE: Children with chronic illnesses have sleep disruption, daytime attention deficits, and impulsivity, and altered blood leukocyte subtypes, sleep-regulating hormones, and pro- and anti-inflammatory cytokines. Children with HIV infection exhibit similar sleep disorders and fatigue, but their effects upon HIV disease progression and immunity are unknown.METHODS: A cohort of 30 HIV+ and 30 HIV-exposed children (8-18 yr.) with detailed clinical database was secured for study. Previously validated questionnaires and test instruments (sleep habits, daytime sleepiness, neurocognition) were administered to HIV+ and control children. Blood from these children was activated with phorbol myristate acetate (PMA) or lipopolysaccharide (LPS) to assess tumor necrosis factor-alpha (TNF-a, pro-inflammatory, sleep-inducing cytokine) and interleukin-10 (IL-10, anti-inflammatory, sleep-inhibiting cytokine) expression in activated T cells to determine the relationship between sleep disturbance, fatigue, and cytokines levels.RESULTS: Psychological testing revealed that there was a positive relationship between plasma IL-10 and neurocognitive functioning in 30 HIV+ children (r = 0.40, p < 0.05). A study of a subgroup of 11 HIV+ children and 10 controls showed that TNF-a was elevated in PMA-stimulated CD3+ T cells (p = 0.049), and IL-10 was lower in LPS-stimulated CD3+ T cells (p = 0.008).CONCLUSIONS: Children with HIV infection demonstrate higher blood levels of the sleep-inducing cytokine, TNF-a; reduced blood levels of the sleep-inhibiting cytokine, IL-10; and neurocognitive deficits. These early results of this clinical study indicate that it may be possible to determine if sleep disorders and fatigue are related with disease progression in HIV+ children. RATIONALE: Children with chronic illnesses have sleep disruption, daytime attention deficits, and impulsivity, and altered blood leukocyte subtypes, sleep-regulating hormones, and pro- and anti-inflammatory cytokines. Children with HIV infection exhibit similar sleep disorders and fatigue, but their effects upon HIV disease progression and immunity are unknown. METHODS: A cohort of 30 HIV+ and 30 HIV-exposed children (8-18 yr.) with detailed clinical database was secured for study. Previously validated questionnaires and test instruments (sleep habits, daytime sleepiness, neurocognition) were administered to HIV+ and control children. Blood from these children was activated with phorbol myristate acetate (PMA) or lipopolysaccharide (LPS) to assess tumor necrosis factor-alpha (TNF-a, pro-inflammatory, sleep-inducing cytokine) and interleukin-10 (IL-10, anti-inflammatory, sleep-inhibiting cytokine) expression in activated T cells to determine the relationship between sleep disturbance, fatigue, and cytokines levels. RESULTS: Psychological testing revealed that there was a positive relationship between plasma IL-10 and neurocognitive functioning in 30 HIV+ children (r = 0.40, p < 0.05). A study of a subgroup of 11 HIV+ children and 10 controls showed that TNF-a was elevated in PMA-stimulated CD3+ T cells (p = 0.049), and IL-10 was lower in LPS-stimulated CD3+ T cells (p = 0.008). CONCLUSIONS: Children with HIV infection demonstrate higher blood levels of the sleep-inducing cytokine, TNF-a; reduced blood levels of the sleep-inhibiting cytokine, IL-10; and neurocognitive deficits. These early results of this clinical study indicate that it may be possible to determine if sleep disorders and fatigue are related with disease progression in HIV+ children.