Increased Circulating Levels of Growth Differentiation Factor 15 in Association with Metabolic Disorders in People Living with HIV Receiving Combined Antiretroviral Therapy.

Pere Domingo,Ferran Torres,Isabel Mur,Joan Villarroya,José M Gallego-Escuredo,Francesc Vidal,Joan C Domingo,Francesc Villarroya,María Del Mar Gutierrez,Noemí Corbacho,María Gracia Mateo,Rubén Cereijo,Laura Campderrós,Marta Giralt

doi:10.3390/jcm11030549

Abstract

Objective: People living with HIV (PLWH) have an increased cardiovascular risk (CVR) owing to dyslipidemia, insulin resistance, metabolic syndrome, and HIV/combination antiretroviral therapy (cART)-associated lipodystrophy (HALS). Atherosclerosis and inflammation are related to growth differentiation factor-15 (GDF15). The relationship between metabolic disturbances, HALS, and CVR with GDF15 in PLWH is not known. Research design and methods: Circulating GDF15 levels in 152 PLWH (with HALS = 60, without HALS = 43, cART-naïve = 49) and 34 healthy controls were assessed in a cross-sectional study. Correlations with lipids, glucose homeostasis, fat distribution, and CVR were explored. Results: PLWH had increased circulating GDF15 levels relative to controls. The increase was the largest in cART-treated PLWH. Age, homeostatic model assessment of insulin resistance 1 (HOMA1-IR), HALS, dyslipidemia, C-reactive protein, and CVR estimated with the Framingham score correlated with GDF15 levels. The GDF15-Framingham correlation was lost after age adjustment. No correlation was found between GDF15 and the D:A:D Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) score estimated CVR. CVR independent predictors were patient group (naïve, HALS−, and HALS+) and cumulated protease inhibitor or nucleoside reverse transcriptase inhibitor exposure. Conclusions: PLWH, especially when cART-treated, has increased GDF15 levels—this increase is associated with dyslipidemia, insulin resistance, metabolic syndrome, HALS, and inflammation-related parameters. GDF15 is unassociated with CVR when age-adjusted.

Highlights

Combination antiretroviral therapy has forever changed the landscape for people living with HIV (PLWH) [1]
A scenario of atherogenic dyslipidemia is depicted in combination antiretroviral therapy (cART)-treated PLWH owing to lipid disturbances and insulin resistance, which may translate into increased cardiovascular risk (CVR) [3]
Patients were eligible whether they had HIV/combination antiretroviral therapy-associated lipodystrophy syndrome (HALS), which was assessed as described in [19] and based mostly on the scales defined by Lichtenstein et al [20], and whether they were on cART

Summary

Introduction

Combination antiretroviral therapy (cART) has forever changed the landscape for people living with HIV (PLWH) [1]. Mortality rates have decreased, and a significant change in the PLWH morbidity pattern has occurred. Morbidity associated with acquired immunodeficiency syndrome (AIDS)-defining conditions have steadily decreased over time, whereas aging-associated co-morbid conditions have gained prominence. Among these conditions, metabolic and fat distribution disturbances, together with increased CVR, stand out [2]. A scenario of atherogenic dyslipidemia is depicted in cART-treated PLWH owing to lipid disturbances and insulin resistance, which may translate into increased CVR [3]. Adipose tissue abnormalities link with an even worse lipid profile [4].

Methods

Results

Conclusion