Differential effects of dolutegravir, bictegravir and raltegravir in adipokines and inflammation markers on human adipocytes

Life Sciences, Journal Year: 2022, Volume and Issue: 308, P. 120948 - 120948

Published: Sept. 9, 2022

To assess the potential direct effects of integrase strand-transfer inhibitors (INsTIs) dolutegravir, bictegravir, and raltegravir, drugs used as treatment for people living with human immunodeficiency virus (PLWH), on adipose cells.Drugs were added to differentiation medium Simpson-Golabi-Behmel syndrome (SGBS) cells morphological adipogenesis was monitored 10 days. Also, adipocytes exposed following (day 14). The gene expression levels selected markers, adipocyte metabolism adipokines, cytokines determined by quantitative-reverse transcription polymerase-chain reaction. release adiponectin leptin into culture measured using specific enzyme-linked immunosorbent assay, interleukin-6 chemokine (CC motif) ligand-2 Multiplex assays.Overall unaltered INsTIs. marker genes (peroxisome proliferator-activated receptor-Ɣ lipoprotein lipase) slightly reduced in dolutegravir-treated differentiating adipocytes. Bictegravir repressed pro-inflammatory Dolutegravir raltegravir increased expression, but only dolutegravir release. had a similar milder effect leptin. Drug mature response dolutegravir.The INsTIs studied do not have significant cell exert distinct secretion adipokines cytokines. These findings will help understand manage INsTI-containing treatments body weight metabolic dysregulation PLWH.

Language: Английский

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Evidence gaps on weight gain in people living with HIV: a scoping review to define a research agenda

BMC Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(1)

Published: April 14, 2023

Combined antiretroviral therapy (cART) dramatically improved survival in people living with HIV (PLWH) but is associated weight gain (WG), raising concern for a possible obesity epidemic PLWH. This scoping review aims to identify the gaps existing evidence on WG PLWH and generate future research agenda.This was conducted according methodology studies reported PRISMA Extension Scoping Review checklist. Articles published English last 10 years indexed Pubmed, WHO Global Index Medicus, or Embase were searched using specific queries focused PLWH.Following selection process, 175 included articles reviewed search available four topics: (I) definition of PLWH, (II) pathogenesis (III) impact ART WG, (IV) correlation clinical outcomes. A summary data enabled us clearly define following agenda: develop data-driven noninvasive assessment methods body fat composition; further investigate interaction between HIV/cART immunity, metabolism, adipose tissue; establish role individual drugs WG; clarify independent cART, HIV, metabolic factors events.The proposed agenda may help fill knowledge that have emerged from this review.

Language: Английский

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Incidence of cardiometabolic outcomes among people living with HIV‐1 initiated on integrase strand transfer inhibitor versus non‐integrase strand transfer inhibitor antiretroviral therapies: a retrospective analysis of insurance claims in the United States

Journal of the International AIDS Society, Journal Year: 2023, Volume and Issue: 26(6)

Published: June 1, 2023

Integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART) has been associated with weight gain, though there is limited information on associations between ART-related gain and cardiometabolic outcomes among people living HIV-1 (PLWH). We, therefore, evaluated risks of incident following INSTI versus non-INSTI-based ART initiation in the United States.We conducted a retrospective study using IBM MarketScan Research Databases (12 August 2012-31 January 2021). Treatment-naïve PLWH initiating (index date) on/after 12 2013 (approval date first second-generation INSTI, dolutegravir) were included censored at regimen switch/discontinuation, end insurance eligibility or data availability. We used inverse probability treatment weights constructed baseline months pre-index) characteristics to account for differences INSTI- non-INSTI-initiating cohorts. Doubly robust hazard ratios (HRs) obtained from weighted multivariable Cox regression compare time (congestive heart failure [CHF], coronary artery disease, myocardial infarction, stroke/transient ischemic attack, hypertension, type II diabetes, lipid disorders, lipodystrophy metabolic syndrome) by INSTI-initiation status.Weighted (mean age = 39 years, 23% female, 70% commercially insured, 30% Medicaid insured) non-INSTI 24% 71% 29% cohorts 7059 7017 PLWH, respectively. The most common INSTI-containing regimens elvitegravir-based (43.4%), dolutegravir-based (33.3%) bictegravir-based (18.4%); non-INSTI-containing darunavir-based (31.5%), rilpivirine-based (30.4%) efavirenz-based (28.3%). Mean±standard deviation follow-up periods 1.5±1.5 1.1±1.2 years cohorts, initiators clinically significantly increased risk experiencing CHF (HR 2.12, 95% confidence interval [CI] 1.08-4.05; p 0.036), infarction 1.79, CI 1.03-5.65; 0.036) disorders 1.26, 1.04-1.58; 0.020); was no evidence an other individual composite outcomes.Over short average period <2 use treatment-naïve several outcomes, such as CHF, compared use. Further research accounting additional potential confounders longer warranted more accurately precisely quantify impact long-term outcomes.

Language: Английский

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Association of alpha-aminoadipic acid with cardiometabolic risk factors in healthy and high-risk individuals

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 7, 2023

Introduction Plasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk type 2 diabetes (T2D) and atherosclerosis. However, little is known about relationship 2-AAA to other cardiometabolic markers in pre-disease states, or setting comorbid disease. Methods We measured circulating using two methods 1) a sample 261 healthy individuals (2-AAA Study), 2) 134 persons comprising 110 treated HIV, without T2D, population at high metabolic disease cardiovascular events despite suppression virus, 24 T2D HIV (HATIM Study). examined associations between plasma health within each cohort. Results discussion observed differences by sex race both cohorts, higher men compared women, Asian Black white (P&lt;0.05). There was no significant difference status HATIM Study. confirmed dyslipidemia where low HDL cholesterol (P&lt;0.001) triglycerides As expected, cohort people pre-diabetes normoglycemia (P&lt;0.001). positively body mass index (BMI) Study, waist circumference measures visceral fat volume (all P&lt;0.05). Further, increased liver Our study confirms as marker those risk, reveals relationships adiposity hepatic steatosis, highlights important race. Further studies are warranted establish molecular mechanisms linking high-risk populations.

Language: Английский

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Consequences of COVID-19 on Adipose Tissue Signatures

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2908 - 2908

Published: March 2, 2024

Since the emergence of coronavirus disease-19 (COVID-19) in 2019, it has been crucial to investigate causes severe cases, particularly higher rates hospitalization and mortality individuals with obesity. Previous findings suggest that adipocytes may play a role adverse COVID-19 outcomes people The impact vaccination infection on adipose tissue (AT) is currently unclear. We therefore analyzed 27 paired biopsies visceral subcutaneous AT from donors Leipzig Obesity BioBank have categorized into three groups (1: no infection/no vaccination; 2: but vaccinated; 3: infected vaccinated) based antibodies spike (indicating vaccination) and/or nucleocapsid proteins. provide additional insights biology through comprehensive histological transcriptome serum proteome analysis. This study demonstrates associated smaller average adipocyte size. gene expression was significantly more pronounced than mainly due immune system-related processes. Serum analysis revealed effects circulating adiponectin, interleukin 6 (IL-6), carbonic anhydrase 5A (CA5A), which are all related obesity blood glucose abnormalities.

Language: Английский

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