Effects of highly active antiretroviral therapy on paediatric metabolite levels

Objectives Highly active antiretroviral therapy (HAART) has extended survival of HIV-infected children into adulthood, raising concerns about long-term metabolic changes in childhood. Methods A longitudinal study of metabolite levels in paediatric HIV-infected patients before and after starting HAART (January 2000 to June 2003). The effects of HAART on nonfasting blood levels of total (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, cholesterol ratio and lactate were analysed using mixed-effects regression. Results A total of 146 children attended 1208 appointments (median 6.7/child). Of these, 99 (68%) were African. At baseline, 75 (51%) were on HAART and had higher TC (4.19 vs 3.49 mmol/L, P < 0.0001), HDL (1.03 vs 0.82 mmol/L, P < 0.0001), and LDL (2.54 vs 2.11 mmol/L, P=0.0003) than those not on HAART. Metabolites increased with time on HAART exposure and then stabilized. At 2 years, TC had increased by 0.93 mmol/L (P < 0.0001), with 29 children (20%) having repeated TC levels above the 95th centile. LDL and HDL had increased by 0.69 and 0.31 mmol/L at 2 years, respectively (both P < 0.0001). Lactates declined with increasing age (-0.06 mmol/L/year, P=0.0001). Conclusions This is the first cohort study to demonstrate significant elevations of HDL as well as LDL in children on HAART. This rise in cardio-protective HDL may represent a positive effect of treatment.