Advanced Glycation End Products Associated With Cardiometabolic Biomarkers in Treated Human Immunodeficiency Virus Infection
Abstract 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 developme...
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Published in | Open forum infectious diseases Vol. 8; no. 10; p. ofab423 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
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Oxford University Press
01.10.2021
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Abstract | Abstract
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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AbstractList | 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.
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.
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 log
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.
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. Abstract 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. BACKGROUNDDespite 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. METHODSACTG 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. RESULTSOverall, 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. CONCLUSIONSAGE 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. |
Author | Moser, Carlee Kelesidis, Theodoros Beisswenger, Paul J Rodriguez, Katherine Howell, Scott K McComsey, Grace A Stein, James H Currier, Judith S El Kamari, Vanessa Brown, Todd T |
AuthorAffiliation | 3 Harvard T. H. Chan School of Public Health , Boston, Massachusetts , USA 6 Johns Hopkins University , Baltimore, Maryland, USA 8 PreventAGE Health Care, LLC , Lebanon, New Hampshire , USA 1 Case Western Reserve University , Cleveland, Ohio , USA 9 Rainbow Babies and Children’s Hospital , Cleveland, Ohio , USA 4 David Geffen School of Medicine at UCLA , Los Angeles, California, USA 7 Geisel School of Medicine at Dartmouth , Hanover, New Hampshire , USA 5 University of Wisconsin , Madison, Wisconsin , USA 2 University Hospitals Cleveland Medical Center , Cleveland, Ohio , USA |
AuthorAffiliation_xml | – name: 1 Case Western Reserve University , Cleveland, Ohio , USA – name: 4 David Geffen School of Medicine at UCLA , Los Angeles, California, USA – name: 8 PreventAGE Health Care, LLC , Lebanon, New Hampshire , USA – name: 7 Geisel School of Medicine at Dartmouth , Hanover, New Hampshire , USA – name: 6 Johns Hopkins University , Baltimore, Maryland, USA – name: 3 Harvard T. H. Chan School of Public Health , Boston, Massachusetts , USA – name: 5 University of Wisconsin , Madison, Wisconsin , USA – name: 9 Rainbow Babies and Children’s Hospital , Cleveland, Ohio , USA – name: 2 University Hospitals Cleveland Medical Center , Cleveland, Ohio , USA |
Author_xml | – sequence: 1 givenname: Vanessa surname: El Kamari fullname: El Kamari, Vanessa organization: Case Western Reserve University, Cleveland, Ohio, USA – sequence: 2 givenname: Katherine surname: Rodriguez fullname: Rodriguez, Katherine organization: Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA – sequence: 3 givenname: Carlee surname: Moser fullname: Moser, Carlee organization: Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA – sequence: 4 givenname: Judith S surname: Currier fullname: Currier, Judith S organization: David Geffen School of Medicine at UCLA, Los Angeles, California,USA – sequence: 5 givenname: Theodoros surname: Kelesidis fullname: Kelesidis, Theodoros organization: David Geffen School of Medicine at UCLA, Los Angeles, California,USA – sequence: 6 givenname: James H surname: Stein fullname: Stein, James H organization: University of Wisconsin, Madison, Wisconsin, USA – sequence: 7 givenname: Todd T surname: Brown fullname: Brown, Todd T organization: Johns Hopkins University, Baltimore, Maryland,USA – sequence: 8 givenname: Scott K surname: Howell fullname: Howell, Scott K organization: Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA – sequence: 9 givenname: Paul J surname: Beisswenger fullname: Beisswenger, Paul J organization: Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA – sequence: 10 givenname: Grace A orcidid: 0000-0003-2690-8888 surname: McComsey fullname: McComsey, Grace A email: grace.mccomsey@uhhospitals.org organization: Case Western Reserve University, Cleveland, Ohio, USA |
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Despite advances in antiretroviral therapy (ART), people living with human immunodeficiency virus (HIV) continue to be at increased risk of... Despite advances in antiretroviral therapy (ART), people living with human immunodeficiency virus (HIV) continue to be at increased risk of cardiometabolic... BACKGROUNDDespite advances in antiretroviral therapy (ART), people living with human immunodeficiency virus (HIV) continue to be at increased risk of... |
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Title | Advanced Glycation End Products Associated With Cardiometabolic Biomarkers in Treated Human Immunodeficiency Virus Infection |
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