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Published on: June 30, 2013
Advanced Glycation End Products Associated With Cardiometabolic Biomarkers in Treated Human Immunodeficiency Virus
Vanessa El Kamari1,2, Katherine Rodriguez3, Carlee Moser3
1Case Western Reserve University, Cleveland, Ohio, USA.
Insights
Antiretroviral therapy (ART) does not reduce advanced glycation end products (AGEs) in people with HIV. Instead, AGE levels increase over time, independently linked to worsening cardiometabolic health.
Area of Science:
- Cardiovascular disease research
- HIV/AIDS research
- Metabolic syndrome research
Background:
- People with HIV (PWH) face higher cardiometabolic risks despite ART.
- Advanced glycation end products (AGEs) contribute to cardiometabolic issues generally.
- The specific role of AGEs in PWH is not well understood.
Purpose of the Study:
- To investigate changes in AGEs after initiating ART in ART-naive PWH.
- To examine the association between AGEs and cardiometabolic markers in PWH.
Main Methods:
- A prospective, open-label, randomized trial (ACTG A5260s) involving 214 ART-naive PWH.
- Participants received one of three ART regimens for 96 weeks.
- Serum AGEs were measured, and linear regression analyzed associations with cIMT, body composition, and insulin resistance.
Main Results:
- Most AGEs remained stable, but methylglyoxal-derived hydroimidazolone 1 (MG-H1) increased significantly after 96 weeks of ART.
- No significant differences in AGE changes were observed across different ART regimens.
- Increased AGE levels correlated with adverse changes in body fat, insulin resistance, and carotid intima-media thickness (cIMT).
Conclusions:
- ART initiation did not lead to a reduction in AGE levels; one AGE (MG-H1) actually increased.
- The accumulation of AGEs over time in PWH on ART is independently associated with worsening cardiometabolic biomarkers.
- These findings highlight the need for strategies to manage AGEs in PWH to mitigate cardiometabolic risks.
Background:
Despite advances in antiretroviral therapy (ART), people living with human immunodeficiency virus (HIV) continue to be at increased risk of cardiometabolic complications compared to HIV-uninfected individuals. Advanced glycation end products (AGEs) are implicated in the development and progression of cardiometabolic complications in the general population. Their role in HIV remains unclear.
Methods:
ACTG A5260s is a prospective open-label randomized trial in which ART-naive people living with HIV were randomized to tenofovir disoproxil fumarate /emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir over 96 weeks. Changes in circulating AGEs with ART initiation were assessed, and linear regression was used to examine the associations between serum AGEs with carotid intima-media thickness (cIMT), visceral and subcutaneous adipose tissue, total fat, lean mass, body mass index, insulin resistance, leptin, and adiponectin.
Results:
Overall, 214 participants were included. Ninety percent were male, 48% were White, the median age was 36 years, median HIV-1 RNA was 4.58 log10 copies/mL, and median CD4 count was 338 cells/µL. Most AGEs remained relatively unchanged following 96 weeks of ART initiation, except for methylglyoxal-derived hydroimidazolone 1 (MG-H1), which increased following 96 weeks of ART (mean fold change, 1.15 [95% confidence interval, 1.02-1.30]). No differences were detected across ART regimens. Increases in AGE levels over time were associated with worsening body fat composition measures, insulin resistance, and cIMT, even after adjusting for clinically relevant factors.
Conclusions:
AGE levels did not decrease following ART initiation. Most AGE levels remained stable, except for MG-H1, which increased. In people with HIV on ART, the accumulation of circulating AGEs over time appears to be independently associated with worsening cardiometabolic biomarkers.Summary: Antiretroviral therapy (ART) does not appear to be effective in reducing advanced glycation end product (AGE) levels. On the contrary, AGE levels seem to increase following ART initiation. Accumulation of AGEs was found to be independently associated with cardiometabolic complications in treated people living with HIV.
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