Plasma Metabolic Signature and Abnormalities in HIV-Infected Individuals on Long-Term Successful Antiretroviral Therapy

被引:53
作者
Babu, Hemalatha [1 ,2 ]
Sperk, Maike [2 ]
Ambikan, Anoop T. [2 ]
Rachel, Gladys [1 ]
Viswanathan, Vinod Kumar [3 ]
Tripathy, Srikanth P. [1 ]
Nowak, Piotr [4 ]
Hanna, Luke Elizabeth [1 ]
Neogi, Ujjwal [2 ]
机构
[1] ICMR, Dept HIV AIDS, Natl Inst Res TB, Chennai 600031, Tamil Nadu, India
[2] Karolinska Inst, Dept Lab Med, Div Clin Microbiol, S-14152 Huddinge, Sweden
[3] Govt Hosp Thorac Med, Tambaram Sanat, Chennai 600047, Tamil Nadu, India
[4] Karolinska Inst, Dept Med, S-14152 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
untargeted metabolomics; HIV; acquired immune deficiency syndrome (AIDS); targeted proteomics; antiretroviral therapy; MUSCLE PROTEIN; INFLAMMATION; PREVALENCE;
D O I
10.3390/metabo9100210
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Targeted metabolomics studies reported metabolic abnormalities in both treated and untreated people living with human immunodeficiency virus (HIV) (PLHIV). The present study aimed to understand the plasma metabolomic changes and predicted the risk of accelerated aging in PLHIV on long-term suppressive antiretroviral therapy (ART) in a case-control study setting and its association with the plasma proteomics biomarkers of inflammation and neurological defects. Plasma samples were obtained from PLHIV on successful long-term ART for more than five years (n = 22) and matched HIV-negative healthy individuals (n = 22, HC herein). Untargeted metabolite profiling was carried out using ultra-high-performance liquid chromatography/mass spectrometry/mass spectrometry (UHPLC/MS/MS). Plasma proteomics profiling was performed using proximity extension assay targeting 184 plasma proteins. A total of 250 metabolites differed significantly (p < 0.05, q < 0.1) between PLHIV and HC. Plasma levels of several essential amino acids except for histidine, branched-chain amino acids, and aromatic amino acids (phenylalanine, tyrosine, tryptophan) were significantly lower in PLHIV compared to HC. Machine-learning prediction of metabolite changes indicated a higher risk of inflammatory and neurological diseases in PLHIV. Metabolic abnormalities were observed in amino-acid levels, energetics, and phospholipids and complex lipids, which may reflect known differences in lipoprotein levels in PLHIV that can resemble metabolic syndrome (MetS).
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页数:16
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