Metabolic complications and treatment of perinatally HIV‐infected children and adolescents

Abstract

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.

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

“…PIs are associated with dyslipidaemia and lipodystrophy 103, 111, 112, 113. However, once‐daily PIs, such as ATV/r and DRV/r, in adults tend to cause fewer lipid abnormalities 114, 115, 116.…”

Efficacy and safety of darunavir (Prezista®) with low-dose ritonavir and other antiretroviral medications in subtype F HIV-1 infected, treatment-experienced subjects in Romania: a post-authorization, open-label, one-cohort, non-interventional, prospective study

“…7,[24][25][26] A slight increase for the mean serum glucose values and cholesterol values was observed in this study. The increase in mean glucose values and total cholesterol values at Week 48 compared to reference (screening) was statistically significant.…”

Aterosclerose Precoce na População Pediátrica Infetada pelo VIH: Revisão da Literatura e Abordagem Clínica

“…Este risco não é totalmente anulado, uma vez que a própria infeção vírica tem também a capacidade de afetar o ADN mitocondrial. 26 A lipohipertrofia, cujo processo etiopatogénico ainda não está bem esclarecido, caracteriza-se por uma distribuição central da adiposidade, com acumulação da gordura no abdómen, tórax e região dorsocervical. É frequentemente um efeito secundário dos inibidores da protease, embora possa existir na ausência de terapêutica antirretrovírica.…”

“…É frequentemente um efeito secundário dos inibidores da protease, embora possa existir na ausência de terapêutica antirretrovírica. [25][26][27][28][29][30][31][32][33][34] Num subgrupo minoritário de doentes, a lipohipertrofia pode coexistir com a lipoatrofia, existindo um padrão misto Revista Científica da Ordem dos Médicos www.actamedicaportuguesa.com de apresentação. A dislipidémia, por sua vez, está presente em 40% a 75% das crianças mais velhas e adolescentes com antecedentes de terapêutica antirretrovírica prolongada.…”

“…Em idade pediátrica é raro encontrar-se diabetes mellitus tipo 2, todavia as outras formas de alteração da homeostasia glicídica podem estar presentes, associando-se frequentemente a lipodistrofia e a síndrome metabólica. 25,26,[40][41][42][43][44][45][46][47] Os diferentes fatores de risco cardiovascular mencionados têm contudo falhado em explicar toda a tendência aterogénica presente nestes doentes e evidência científica corrobora que a predisposição aterosclerótica se mantém, mesmo após a correção dos fatores de risco convencionais. 48,49 O estudo SMART é exemplo do exposto.…”