Multi-Parametric Diagnostic Approach and Potential Markers of Early Onset Subclinical Cardiovascular Disease in a Cohort of Children, Adolescents and Young Adults Vertically Infected with HIV on cART

Abstract

Background: HIV infection and lifelong cART are responsible of an increase in cardiovascular risk. The aim of this study was to describe the subclinical cardiovascular disease and to identify early markers of cardiovascular damage in adolescents and young adults vertically infected with HIV on cART, through an innovative multi-parametric approach. Methods: We enrolled 52 patients vertically infected with HIV. Demographic records, traditional cardiovascular risk factors, laboratory findings and echocardiographic measurements were collected in a one-year routine follow up. The echocardiographic examination included measurements of the 2D and 3D ejection fraction (EF), E/A ratio, E/E′ ratio, carotid intima media thickness (cIMT), flow-mediated dilation (FMD) and global longitudinal strain (GLS). Results: At the time of enrolment, all the patients were on cART therapy. The viral load was suppressed in 95% of them. EF was normal in 94.2% of patients (66 ± 7.2%), and GLS (mean value: −20.0 ± 2.5%) was reduced in 29% of patients. The cIMT mean value was higher than the 95th centile for sex and age in 73%, and FMD was impaired in 45% of patients. Clinically evident disease was found in three patients: dilative cardiomyopathy in one, thoracic-abdominal aneurysm Crawford type II with a bilateral carotid dilation in one and carotid plaque with 30% of stenosis in a third patient. Conclusions: This study confirms the presence of clinical and subclinical cardiovascular disease in a very young population vertically infected with HIV, underlining the importance of an early, multi-parametric cardiovascular follow up.

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

“…Overall, four studies consistently reported impaired endothelial function (either lower RHI or FMD) in PHIV group compared to uninfected controls [28,29,34,39]. Castaldi et al, reported that 45% of children with PHIV had abnormal FMD [32]. ART-treated participants had similar endothelial function to those ART-naïve as reported by two studies [27,29].…”

“…Four studies reported contrasting findings of similar IMT between PHIV and uninfected controls [29,46,33,40]. One study did not have a comparator group and reported that more than two-thirds of children with PHIV had abnormal IMT [32]. We conducted a meta-analysis comparing IMT between PHIV and uninfected controls using studies assessing carotid IMT on the far walls as recommended in official guidelines [47].…”

“…A total of six studies investigated endothelial function by measuring either reactive hyperaemic index (RHI) in two studies or flow-mediated dilation (FMD) of the brachial artery in 4 studies [27][28][29]32,34,39]. Overall, four studies consistently reported impaired endothelial function (either lower RHI or FMD) in PHIV group compared to uninfected controls [28,29,34,39].…”

Reduced probability of improving viro‐immunological state in subjects with vertical transmission of HIV reaching adult age: A multicenter retrospective cohort study

“…Several studies showed how these individuals are characterized by a worse course of HIV infection, with a higher incidence of acquired immunodeficiency syndrome (AIDS) events, higher AIDS‐related mortality, as well as a higher incidence of comorbidities linked to the systemic effects of HIV infection along with a prolonged proinflammatory state, and long‐term toxicities of antiretrovirals. 4 , 5 , 6 , 7 , 8 , 9 , 10 …”

“…Several studies showed how these individuals are characterized by a worse course of HIV infection, with a higher incidence of acquired immunodeficiency syndrome (AIDS) events, higher AIDS-related mortality, as well as a higher incidence of comorbidities linked to the systemic effects of HIV infection along with a prolonged proinflammatory state, and long-term toxicities of antiretrovirals. [4][5][6][7][8][9][10] The main driver of AIDS-related mortality and AIDS occurrence reduction are, on one hand, the effectiveness of antiretroviral therapy and, on the other hand, the achievement of a full immunological recovery with values of CD4+ T-cell count > 500 cells/mm³ and a CD4+/CD8+ ratio ≥ 1. [11][12][13][14] These parameters, in fact, do not only indirectly express the state of immune system, but they are also surrogate markers of immuneactivation and chronic inflammation.…”