Effects of paediatric HIV infection on childhood vasculature.

Abstract

Human immunodeficiency virus (HIV) infection may alter childhood vascular properties and influence future cardiovascular risk. Whether vascular changes are associated with HIV infection per se or antiretroviral therapy (ART) is unknown. We investigated the effects of ART-naive or ART-exposed HIV infection in children on childhood vascular characteristics. We performed vascular ultrasound to measure carotid intima media thickness (cIMT), distensibility, and elastic modulus on 114 children with vertically acquired HIV infection (56 ART-naive, 58 ART treated) and 51 healthy children in Jakarta, Indonesia. Children also underwent clinical and blood examinations. We used general linear modelling to estimate associations between HIV infection/treatment status and vascular characteristics with adjustment for confounders or possible mediators. Vascular measurements were successful in 42 ART-naive HIV-infected [median age 4.0 years (min 0.4-max 11.5)]; 53 ART-treated HIV infected [5.7 years (0.6-12.2), median ART duration 2.4 years (0.1-9.9)]; and 48 healthy children, 6.5 years (2.4-14.0). The ART-naive HIV infected had thicker cIMT (difference 70.4 µm, 95% CI 32.1-108.7, P < 0.001), adjusted for age, sex, socioeconomic status, parental smoking, body mass index, systolic and diastolic blood pressure, LDL cholesterol, and HbA1c. Addition of high-sensitivity C-reactive protein (hs-CRP) level to the model did not affect the results (71.6 µm, 31.9-111.2, P = 0.001). The ART-exposed children had similar cIMT dimensions to healthy children. Distensibility was not significantly different between HIV infected, either ART-naive or -exposed, and healthy children, but adjusted analysis including only ART-exposed children with controlled HIV (CD4+ ≥200/mm3 or CD4+ ≥15%) showed that the ART-exposed had an increased elastic modulus (difference 37.9 kPa, 95% CI 6.5-69.3, P = 0.02), and following adjustment for hs-CRP (35.5 kPa, 95% CI 4.2-66.8, P = 0.03). ART-naive HIV infection in children is associated with increased cIMT. Children with ART-controlled HIV may have increased arterial stiffness, although further confirmation is required.