This is an investigation into lipodystrophy syndrome (LS), defined as specific body fat alterations (BFA) and/or metabolic abnormality (MA), in HIV-infected children. Antiretroviral therapy (ART) has resulted in improved disease-free survival in HIV-infected individuals, but is an established risk factor for LS. The metabolic profile seen in LS patients is similar to that seen in the early stages of cardiovascular disease. As ART coverage improves, and because treatment is life-long, the importance of LS will become more relevant, especially as treated children survive into adulthood, and accumulate longer durations of exposure to multiple drugs. Data from a prospective European multi-centre cohort of 426 HIV-infected subjects aged 2-18, has been analysed. The manifestation of LS using clearly-defined phenotypes is described, with estimates of prevalence and incidence. Risk factors for LS were identified in logistic, and proportional hazards regression models. The temporal relationship between BFA and MA was explored, and the impact of LS on serum lipids modelled using a multi-level approach. Finally interventions used to manage symptoms of LS were described. The prevalence of LS at recruitment (median age 12.2 years) was 56.5% (95% CI: 51.7, 61.3): half had BFA alone, one-quarter had MA alone, and one-quarter had both. Over follow-up (median: 4.2 years) the incidence of BFA was 8.0 per 100 person-years (95% CI: 6.0, 10.7) and that of MA was 4.1 per 100 person-years (95% CI: 2.8, 5.9). Significant, independent risk factors associated with increased risk of LS outcomes included protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) use, age, clinical status, and White ethnicity. Decreased risk was associated with immunosuppression and detectable viral load. Several factors were associated with increased pro-atherosclerotic lipid concentrations over follow-up: however, NNRTI use and female sex were significantly associated with increased antiatherosclerotic HDL-cholesterol. This thesis used data from a unique large prospective cohort to underline the increasing significance of LS in HIV-infected children and adolescents
