Metabolic complications and treatment of perinatally HIV-infected children and adolescents.

The benefits of long-term antiretroviral therapy (ART) are recognized all over the world with infected children maturing into adults and HIV infection becoming a chronic illness. However, the improved survival is associated with serious metabolic complications, including lipodystrophy (LD), dyslipidemia, insulin resistance, lactic acidosis and bone loss. In addition, the dyslipidemia mainly seen with protease inhibitors may increase the risk of cardiovascular disease in adulthood and potentially in children as they mature into adults. Nucleoside reverse transcriptase inhibitors, particularly stavudine, zidovudine and didanosine are linked to development of LD and lactic acidosis. Perinatally infected children initiate ART early in life; they require lifelong therapy with multiple drug regimens leading to varying toxicities, all potentially impacting their quality of life. LD has a significant impact on the mental health of older children and adolescents leading to poor self-image, depression and subsequent poor adherence to therapy. Reduced bone mineral density (BMD) is reported in both adults and children on ART with the potential for children to develop more serious bone complications than adults due to their rapid growth spurts and puberty. The role of vitamin D in HIV-associated osteopenia and osteoporosis is not clear and needs further study. Most resource-limited settings are unable to monitor lipid profiles or BMD, exposing infected children and adolescents to on-going toxicities with unclear long-term consequences. Improved interventions are urgently needed to prevent and manage these metabolic complications. Longitudinal cohort studies in this area should remain a priority, particularly in resource-limited settings where the majority of infected children reside.