Earlier antiretroviral initiation is independently associated with better arterial stiffness in children living with perinatally acquired HIV with sustained viral suppression in Mozambique

Abstract

Background: Cardiovascular disease is a major driver of morbidity and mortality in adults living with HIV. The drivers of cardiovascular disease in children living with perinatally acquired HIV (PHIV) with sustained HIV viral suppression are unclear.Objectives: We explored the contribution of HIV-specific risk factors to arterial stiffness independently of traditional risk factors (metabolic syndrome [MetS]) in prepubertal children with PHIV with sustained viral suppression in a low-income country in Africa.Method: For this cross-sectional analysis, arterial stiffness was assessed by pulse wave velocity z-score (PWVz), measured using a Vicorder device. Metabolic syndrome components were measured. We retrospectively collected the antiretroviral therapy (ART) exposures, HIV stage, CD4 count and HIV viral load. A multivariate linear regression model was constructed for MetS components, retaining age and gender as obligatory variables. We then added HIV-related metrics to assess whether these had an independent or additive effect.Results: We studied 77 virally suppressed children with PHIV without evidence of cardiovascular disease (from medical history and physical examination). In the initial model, the PWVz was independently associated with each MetS component. The PWVz was higher in participants with proportionally greater visceral fat (waist/height ratio), elevated lipids (triglyceride/high-density lipoprotein ratio) and insulin resistance (log homeostatic model assessment [HOMA]). The addition of age at ART initiation increased the model R2 value from 0.36 to 0.43. In the resulting model, younger age at ART initiation was independently associated with a better PWVz (P 0.001).Conclusion: Earlier ART initiation was independently associated with lower large artery stiffness. This effect was independent of the effect of elevated lipids, visceral fat and insulin resistance.

An Overview of Vascular Dysfunction and Determinants: The Case of Children of African Ancestry

“…The PWV increased with cumulative time on ART in children living with HIV among primary school children in Cape Town, Western Cape Province of South Africa (154). In Mozambique, a study conducted among children with perinality-acquired HIV finds that PWV is higher in participants with increased visceral fat, elevated lipids, and insulin resistance (155). A study carried out in Egypt among 74 obese children aged 6-18 years finds a significant positive correlation between cIMT and BMI.…”

The effect of perinatal HIV and antiretroviral therapy on vascular structure and function in young people: A systematic review and meta-analysis

“…Arterial stiffness was assessed through pulse wave velocity (PWV) by six studies [27,36,38,43,30,31]. Higher PWV in PHIV compared to uninfected controls was reported in two studies suggesting stiffer arteries [38,43].…”

“…However, Dirajlal-Fargo et al and Mellin et al, found no difference in arterial stiffness between PHIV group and uninfected controls [36,30]. One study did not have a comparator group and found that a fifth of children with PHIV had abnormal PWV [31]. According to Gleason et al, participants who were taking efavirenz and ritonavir-boosted lopinavir (LPV/r) had stiffer arteries (higher PWV) compared to those receiving nevirapine.…”

“…Limitations of this review are lack of a robust meta-analysis of the different vascular measures as only a few studies were conducted for arterial stiffness and endothelial function assessment. Notably, different tools were used to assess for vascular function, and in some studies different regions were examined [38,30,31,34], which further hindered pooling of results in a meta-analysis. There was substantial heterogeneity of studies included in the meta-analysis.…”