Dyslipidemia, chronic inflammation, and subclinical atherosclerosis in children and adolescents infected with HIV: The PositHIVe Health Study

Abstract

HIV-infected children and adolescents may be at risk for cardiovascular disease due to chronic inflammation and exacerbation of risk factors. The aim of this study was as follows: 1) compare cardiovascular risk factors, chronic inflammation, and carotid intima-media thickness (IMTc) between the HIV and control groups; 2) determine the association of HIV and antiretroviral (ART) regimens with cardiovascular risk factors, chronic inflammation, and IMTc; and 3) identify variables associated with elevated IMTc. Cross-sectional analysis of 130 children and adolescents, 8–15 years of age, divided into HIV-infected (n = 65) and healthy control (n = 65) participants. Body fat, blood pressure, glycemia, insulin, and glycated hemoglobin, total cholesterol and fractions (LDL-C and HDL-C), triglycerides, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and the IMTc were measured. The results showed HIV-infected children and adolescents had higher levels of glycemia (87.9 vs. 75.9 mg.dL−1, p< 0.001), LDL-c (94.7 vs. 79.5 mg.dL−1, p = 0.010), triglycerides (101.2 vs. 61.6 mg.dL−1, p< 0.001), CRP (1.6 vs. 1.0 mg.L−1, p = 0.007), IL-6 (1.42 vs. 0.01 pg.mL−1, p< 0.001), TNF-α (0.49 vs. 0.01 pg.mL−1, p< 0.001), mean IMTc (0.526 vs. 0.499 mm, p = 0.009), and lower HDL-c (53.7 vs. 69.4 mg.dL−1, p< 0.001) compared to controls. Systolic blood pressure (β = 0.006, p = 0.004) and TNF-α (β = −0.033, p = 0.029) accounted for 16% of IMTc variability in HIV-infected children and adolescents. In patients using protease inhibitors-based ART, male gender (β = −0.186, p = 0.008), trunk body fat (β = −0.011, p = 0.006), glucose (β = 0.005, p = 0.046), and IL-6 (β = 0.017, p = 0.039) accounted for 28% of IMTc variability. HIV-infected children and adolescents may be at risk for premature atherosclerosis due to chronic inflammation and dyslipidemia. Interventions with the potential to improve lipid profile, mitigate inflammation, and reduce cardiovascular risk are needed.

Disease- and Treatment-related Morbidity in Adolescents With Perinatal HIV Infection in Asia

“…17,18 Of note, metabolic/endocrine events dominated treatmentrelated morbidities in our PHIVA cohort, representing about half of all reported treatment-related events. This is consistent with the established concerns regarding the metabolic effects of ART in children and adolescents, 9,11,19 and are an important consideration when designing optimal long-term ART regimens, particularly given the increased risk of cardiovascular disease for adults living with HIV. 20,21 The younger adolescent age group had a significantly higher rate of overall morbidity compared to their older counterparts, which is mainly attributable to higher disease-related morbidity.…”

“…8 There have been particular concerns regarding the metabolic impact of long-term ART, initially around lipodystrophy associated with earlier ART agents to dyslipidemia and insulin resistance 9,10 associated with protease inhibitors (PIs) and their impact on long-term cardiovascular health. 11 Much of the morbidity data to date from low-and middle-income country (LMIC) settings have been presented for broader pediatric populations, with limited data exclusively relating to PHIVA. 1,2 There remains a need for more comprehensive data regarding long-term clinical complications PHIVA face, 12,13 to assist HIV health care providers to prevent, monitor, and manage them, and optimise models of adolescent HIV care.…”

Metabolic syndrome, biochemical markers, and body composition in youth living with perinatal HIV infection on antiretroviral treatment

“…We documented that 35.9% of PHIV-youths in our study had high hsCRP, which inferred risk of CVD. This corroborates a Brazilian study which reported a significantly higher CRP than healthy control among PHIV-children, mean age 12.2 years [25]. However, a Spanish study in PHIV-children with a mean age of 14.2 years and a mean duration of 3 years on ART, reported that the mean hsCRP level in those without metabolic disturbances was similar to non HIV controls [26].…”

Immune Activation, Inflammation, and Non-AIDS Co-Morbidities in HIV-Infected Patients under Long-Term ART

“…Nowadays, non-AIDS co-morbidities represent one of the major causes of morbidity and mortality in perHIV patients compared with age-matched HCs [132,133]. Indeed, perHIV patients present higher levels of glycemia, tryglicerides, CRP, TNF-α, systolic blood pressure, and carotid intima-media thickness compared with age-matched HCs, making them a group at higher risk of developing premature atherosclerosis, CVDs, and MetS [134].…”