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Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s
Background. Antiretroviral therapy (ART) can alter glucose metabolism, but little data exist on the association of raltegravir (RAL) with insulin resistance. Methods. A5260s was a substudy of A5257, a prospective open-label randomized trial in which human immunodeficiency virus (HIV)-infected treatm...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047417/ https://www.ncbi.nlm.nih.gov/pubmed/27704026 http://dx.doi.org/10.1093/ofid/ofw174 |
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author | Dirajlal-Fargo, Sahera Moser, Carlee Brown, Todd T. Kelesidis, Theodoros Dube, Michael P. Stein, James H. Currier, Judith McComsey, Grace A. |
author_facet | Dirajlal-Fargo, Sahera Moser, Carlee Brown, Todd T. Kelesidis, Theodoros Dube, Michael P. Stein, James H. Currier, Judith McComsey, Grace A. |
author_sort | Dirajlal-Fargo, Sahera |
collection | PubMed |
description | Background. Antiretroviral therapy (ART) can alter glucose metabolism, but little data exist on the association of raltegravir (RAL) with insulin resistance. Methods. A5260s was a substudy of A5257, a prospective open-label randomized trial in which human immunodeficiency virus (HIV)-infected treatment-naive participants were randomized to tenofovir-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or RAL over 96 weeks. Baseline and changes in insulin resistance as estimated by the homeostatic model assessment of insulin resistance (HOMA-IR) were assessed. Wilcoxon rank-sum tests were used to assess shifts in the distribution of fold increase from baseline between treatment arms, and Spearman correlation was used to assess associations between HOMA-IR and measures of inflammation and body composition. Results. Three hundred twenty-eight participants were randomized; 90% were male, baseline median age was 36, HIV ribonucleic acid copies were 4.55 log(10) copies/mL, and CD4 cell count was 349/mm(3). Overall, HOMA-IR increased significantly after 4 weeks (1.9-fold change; 95% confidence interval, 1.73–2.05) then plateaued over the remainder of the study. Changes in HOMA-IR were not different between the arms (P ≥ .23). Changes in HOMA-IR were associated with changes in body mass index at weeks 48 and 96 (r = 0.12–0.22; P ≤ .04). There was a trend with increases in HOMA-IR and increases in visceral abdominal fat at week 96 (r = 0.12; P = .06). At 48 and 96 weeks, HOMA-IR correlated with interleukin-6, high-sensitivity C-reactive protein, and soluble CD163 (r = 0.16–0.27; P ≤ .003). Conclusions. Insulin resistance increased rapidly and then plateaued in treatment-naive participants initiating ART with TDF/FTC, and no differences were found with RAL when compared with ATV/r or DRV/r. |
format | Online Article Text |
id | pubmed-5047417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-50474172016-10-04 Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s Dirajlal-Fargo, Sahera Moser, Carlee Brown, Todd T. Kelesidis, Theodoros Dube, Michael P. Stein, James H. Currier, Judith McComsey, Grace A. Open Forum Infect Dis Major Articles Background. Antiretroviral therapy (ART) can alter glucose metabolism, but little data exist on the association of raltegravir (RAL) with insulin resistance. Methods. A5260s was a substudy of A5257, a prospective open-label randomized trial in which human immunodeficiency virus (HIV)-infected treatment-naive participants were randomized to tenofovir-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or RAL over 96 weeks. Baseline and changes in insulin resistance as estimated by the homeostatic model assessment of insulin resistance (HOMA-IR) were assessed. Wilcoxon rank-sum tests were used to assess shifts in the distribution of fold increase from baseline between treatment arms, and Spearman correlation was used to assess associations between HOMA-IR and measures of inflammation and body composition. Results. Three hundred twenty-eight participants were randomized; 90% were male, baseline median age was 36, HIV ribonucleic acid copies were 4.55 log(10) copies/mL, and CD4 cell count was 349/mm(3). Overall, HOMA-IR increased significantly after 4 weeks (1.9-fold change; 95% confidence interval, 1.73–2.05) then plateaued over the remainder of the study. Changes in HOMA-IR were not different between the arms (P ≥ .23). Changes in HOMA-IR were associated with changes in body mass index at weeks 48 and 96 (r = 0.12–0.22; P ≤ .04). There was a trend with increases in HOMA-IR and increases in visceral abdominal fat at week 96 (r = 0.12; P = .06). At 48 and 96 weeks, HOMA-IR correlated with interleukin-6, high-sensitivity C-reactive protein, and soluble CD163 (r = 0.16–0.27; P ≤ .003). Conclusions. Insulin resistance increased rapidly and then plateaued in treatment-naive participants initiating ART with TDF/FTC, and no differences were found with RAL when compared with ATV/r or DRV/r. Oxford University Press 2016-08-29 /pmc/articles/PMC5047417/ /pubmed/27704026 http://dx.doi.org/10.1093/ofid/ofw174 Text en © The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. |
spellingShingle | Major Articles Dirajlal-Fargo, Sahera Moser, Carlee Brown, Todd T. Kelesidis, Theodoros Dube, Michael P. Stein, James H. Currier, Judith McComsey, Grace A. Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s |
title | Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s |
title_full | Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s |
title_fullStr | Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s |
title_full_unstemmed | Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s |
title_short | Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s |
title_sort | changes in insulin resistance after initiation of raltegravir or protease inhibitors with tenofovir-emtricitabine: aids clinical trials group a5260s |
topic | Major Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047417/ https://www.ncbi.nlm.nih.gov/pubmed/27704026 http://dx.doi.org/10.1093/ofid/ofw174 |
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