Long-term lipoprotein and lipid profiles and association with metabolic risk markers in youth with perinatally acquired HIV and matched controls: a 10-year comparative cohort study

van der Post et al. Lipids in Health and Disease https://doi.org/10.1186/s12944-025-02718-z (2025) 24:344 Lipids in Health and Disease Open Access RESEARCH Long-term lipoprotein and lipid profiles and association with metabolic risk markers in youth with perinatally acquired HIV and matched controls: a 10-year comparative cohort study Julie van der Post1,2,3*, Ben van Nieuwland1, Samera Kassa Almu1, Charlotte Blokhuis4, Malon van den Hof2,5, Dasja Pajkrt1,2,3 and Jason G. van Genderen1,2,3 Abstract Background Youth with perinatally acquired HIV (PHIV) are at risk for cardiovascular disease (CVD) despite combination anti-retroviral therapy (cART). Longitudinal data on the impact of HIV and cART on lipid metabolism and CVD risk in PHIV youth is limited. We investigated lipid and lipoprotein levels in PHIV youth and matched controls over time and examined associations with cART and metabolic syndrome (MetS) markers. Methods We included 32 PHIV and 36 controls at three time points: 2013, 2018 and 2023. In 2023, we assessed lipid profiles cross-sectionally in a larger cohort of 53 PHIV participants and 45 controls. Measurements included lipoprotein (a) (Lp(a)), apolipoprotein B (ApoB), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), reduced high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) and markers related to MetS risk. Results The median age was 21.7 years (IQR 16.7–25.2) for PHIV participants and 21.2 years (16.8—22.3) for controls in 2023 for longitudinal assessment. No significant differences in lipid or lipoprotein levels were observed over time (p values > 0.05). TG levels were significantly higher in PHIV participants at second assessment (p = 0.043), but other levels were comparable (p values > 0.05). Higher Lp(a) levels were associated with higher LDL-C and ApoB levels, however associations were significantly weakened among PHIV participants. Furthermore, protease inhibitor (PI) use was associated with elevated TC, TG and LDL-C. During cross-sectional assessment median age was 17.4 years (IQR 12.7–22.4) and 19.1 years (IQR 15.0—21.8) for PHIV youth and controls. Lipid and MetS markers were comparable between groups (p values > 0.05). Conclusion PHIV youth on cART showed similar lipid and lipoprotein levels over time compared to matched controls. Lp(a) associations with lipid markers were weakened for PHIV youth and PI use was associated with lipid alterations. Our results imply that while lipid profiles, including Lp(a), are important components of cardiovascular *Correspondence: Julie van der Post Full list of author information is available at the end of the article © The Author(s) 2025. 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To view a copy of this licence, visit http://creati vecommons.org/licenses/by-nc-nd/4.0/. Post van der et al. Lipids in Health and Disease (2025) 24:344 Page 2 of 13 health monitoring, the increased CVD risk observed in PHIV youth may be more substantially influenced by diseasespecific or broader pathophysiological mechanisms related to HIV-infection and treatment. Trial registration Dutch clinical trial registration: Overview of Medical Research in the Netherlands (OMON) (ID: NL-OMON53727). Keywords Human immunodeficiency virus, Cardiovascular disease, Antiretroviral therapy, Lipoproteins, Lipid profiles Introduction With the introduction of combination antiretroviral therapy (cART), survival rates of children growing up with perinatally acquired HIV (PHIV) have drastically improved [1]. As PHIV youth are transitioning into adult care, the impact of HIV- and cART-related long-term complications and prevention strategies have become important areas of research [2, 3]. Despite successful viral suppression, PHIV youth remain at increased risk for possible long-term comorbidities, including cardiovascular disease (CVD) and metabolic complications later in life [4–7]. The global burden of HIV-related CVD has tripled in the past two decades and is expected to increase further [5, 6]. The pathophysiology of increased HIV-associated CVD risk possibly arises from HIV-specific mechanisms (e.g. chronic inflammation, immune activation, vascular dysfunction) and potential cardiovascular side effects of lifelong cART in combination with traditional CVD risk factors (e.g. smoking, hypertension) [8–11]. Research in HIV adults have clearly linked HIV to the development of CVD including premature coronary aging, atherosclerosis, diabetes, and heart failure [8, 12–15]. Although research in PHIV youth remains limited, studies suggest an increased risk of metabolic and subclinical cardiac abnormalities compared to HIV-negative controls (e.g. lipodystrophy, endothelial dysfunction and left ventricular hypertrophy) [16–18]. Other metabolic abnormalities observed in PHIV youth include features of metabolic syndrome (MetS) and dyslipidemia such as insulin resistance, elevated triglycerides (TG), elevated low-density lipoprotein cholesterol (LDL-C) and reduced high-density lipoprotein cholesterol (HDL-C) [17–23]. MetS is strongly correlated with (pre)diabetes and increased CVD risk in the general population accompanied with characteristic changes in physical and laboratory measurements [24, 25]. Several cardiometabolic laboratory markers including glucose levels to assess insulin resistance, LDL-C, HDL-C, TG, apolipoproteins B and A1 (Apo B and ApoA1), and lipoprotein (a) ((Lp(a)) are applied to determine MetS and/or CVD risk in the general population [26–28]. Elevated Lp(a) is an independent risk factor for CVD, contributing to atherogenesis and thrombosis [29]. Lp(a) levels above 50 mg/dL (125 nmol/L) indicate increased CVD risk, levels between 30–50 mg/dL (75–125 nmol/L) indicate intermediate risk and warrant further assessment of additional CVD risk factors [28]. In children, Lp(a) levels above 30 mg/dL have been associated with elevated risk of arterial ischemic stroke [28]. In addition to plasma glucose levels, glycated haemoglobin (HbA1c) is used to diagnose (pre)diabetes and MetS, though its accuracy in HIV is unclear and ma (...truncated)