Associations of proinflammatory cytokine levels with lipid profiles, growth, and body composition in HIV-infected children initiating or changing antiretroviral therapy

Elevated levels of pro-inflammatory cytokines (PIC) TNF-α, IL-1 β and IL-6 have been detected in the blood of HIV-infected individuals. In infected children PIC have been implicated in loss of lean body mass1 and growth impairment.2 Decreases in TNF-α levels have been associated with initiation of effective combination antiretroviral therapy (ART)3 while persistent TNF-α activation has been associated with virologic and immunologic treatment failure in HIV-infected adults.4 However, little information is available on the association of PIC in HIV-infected children receiving ART.5 Poor growth is a common manifestation of HIV infection in children6,7,8,9,10 and predicts survival, regardless of plasma viral load (VL), and CD4+ lymphocyte count.11 Yet, the pathophysiology of growth impairment in HIV-infection remains poorly understood as are the relationships between PIC and growth, markers of growth hormone activity, VL, CD4+, and ART. In addition, little is understood regarding associations of these factors with serum lipid levels, which have been reported to be elevated in children receiving ART.12 The weight of scientific evidence to date, almost exclusively from adults, suggests that PIC are up-regulated in HIV-infection, and are associated with increased HIV replication and adverse metabolic consequences. We undertook this study to address the dearth of knowledge regarding associations of PIC with measures of disease progression, growth, body composition and metabolism in HIV-infected children. We hypothesized that children responding to ART with favorable virologic and immunologic response measures would exhibit PIC reductions associated with improved growth, body composition, and lipid profiles.