High Prevalence of Dyslipidemia and Insulin Resistance in HIV-infected Prepubertal African Children on Antiretroviral Therapy

Abstract

BACKGROUND Data describing the true extent of antiretroviral therapy (ART)-induced dyslipidemia and insulin resistance in perinatally-infected children on ART in Africa is sparse. METHODS Fasting total cholesterol, LDL, HDL, triglycerides, insulin and glucose were performed on the first 100, of 190 pediatric ART clinic attendees. Diet assessment was performed by a trained dietician. Lipoatrophy was formally graded by consensus between two expert HIV pediatricians. Durations of previous ART exposures, clinical stage, pre-ART viral load, nadir and current CD4 were recorded. Dual energy X-ray Absorptiometry (DEXA) was performed on a subset of 42 patients selected semi-randomly. RESULTS Prevalences of insulin resistance, abnormal total cholesterol, LDL, HDL and triglyceride were 10%, 13%, 12%, 13 % and 9% respectively. Overall, 40% had at least one lipid abnormality or insulin resistance. Adjusted mean LDL cholesterol increased by 0.24mmol/L for each additional year of cumulative lopinavir/r exposure (p=0.03) after correcting for age, gender, body mass index, previous stavudine exposure, age at ART initiation, dietary fat and refined carbohydrate, while adjusted mean LDL cholesterol was 0.9mmol/L higher in children exposed to efavirenz within the previous six months (p=0.02). Adjusting for age, gender and ethnicity, DEXA revealed that greater trunk fat and lower peripheral subcutaneous fat were associated with elevated triglycerides but not with total cholesterol, LDL, HDL or HOMA. Similarly, the presence of visually obvious lipoatrophy was associated with elevated triglycerides but not with total cholesterol, LDL, HDL, HOMA or lactate. CONCLUSIONS Prevalences of insulin resistance and dyslipidemia were high. Cumulative lopinovir is an independent risk factor for dyslipidemia, with efavirenz exposure having only transitory effect.

Low prevalence of lipodystrophy in HIV-infected Senegalese children on long-term antiretroviral treatment: the ANRS 12279 MAGGSEN Pediatric Cohort Study

“…The rate of hypercholesterolemia was high, mainly led by elevated LDL-cholesterol, while hypertriglyceridemia was marginal in the cohort. As have others [ 13 , 48 ], we found no association between lipodystrophy and dyslipidemia. Longitudinal analyses of blood lipid profile evolution are currently ongoing in the cohort (data not shown).…”

Craniofacial morphology of HIV-positive children and adolescents undergoing antiretroviral therapy: A pilot study

“…43 Moreover, the long-term use of HAART may be responsible for systemic alterations that affect the growth of these children. 5,7,12,13 On the other hand, HAART emerged as a solution to the deleterious effects caused by the virus by diminishing the circulating viral load. Parallel to this, the immunologic reconstitution induced by the use of antiretroviral agents, expressed by the increase in CD41 T lymphocytes, has allowed patients to be clinically more stable, with reductions in opportunist infections that could cause malnutrition.…”

“…[1][2][3][4] Although most reports on the adverse effects of the medication were related to adults, HIV1 children have also been affected. These changes identified in the pediatric population include mitochondrial toxicity, 5 lipodystrophy, 6 dyslipidemias and insulin resistance, 7 hypertension, 8 liver dysfunction, 9 cardiac dysfunction, 10 increased risk for cardiovascular 11 and cerebrovascular 12 diseases, renal toxicity, and low bone mineral density. 12 Perinatally, HIV infected children also showed a growth deficit resulting in reduced height.…”

Prevalence of Dyslipidaemia in HIV-infected Children Treated with Protease Inhibitors in South Africa

“…(20)(21)(22)(23) Dyslipidaemia was defined as hypercholesterolaemia (total cholesterol ≥5.13 mmol/l) and/or hypertriglyceridaemia (total triglycerides ≥1.69 mmol/l). (25) This definition applied to two previous South African studies, (4,19) and the studies on American children that derived these values used non-fasting lipids. (26,27) At 12 and 24 months, we chose a log VL less than 4 (10,000 copies/ml) as a proxy for significant drug pressure which was inclusive of VLs that were suppressed.…”

“…Both studied very young children (<6 years of age) with the latter focusing on the lipodystrophy syndrome. (4,19) The prevalence of dyslipidaemia was reported to be 36% and 40%, respectively. Therefore, we sought to determine the prevalence of dyslipidaemia in African children (0-19 years) treated with second-generation PIs and the risk factors associated with development of dyslipidaemia.…”