A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness

James H. Stein, Heather J. Ribaudo, Howard N. Hodis, Todd T Brown, Thuy Tien T Tran, Mingzhu Yan, Elizabeth Lauer Brodell, Theodore Kelesidis, Grace A. McComsey, Michael P. Dube, Robert L. Murphy, Judith S. Currier

Research output: Contribution to journalArticle

Abstract

Objective: This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima-media thickness (IMT) over 3 years. Design: Randomized clinical trial. Setting: Multicenter (26 institutions). Patients: ART-naive HIV-infected individuals (n = 328) without known cardiovascular disease or diabetes mellitus. Intervention: Random assignment to tenofovir/emtricitabine along with atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). Main outcome measures: Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression. Results: HIV-1 RNA suppression rates were high in all arms (>85%) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95% confidence interval (5.6, 10.8)(Jim/year] than DRV/r [12.9 (10.3, 15.5)μum/year, P=0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2)μm/year, P=0.15 vs. ATV/r; P=0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates. Conclusion: In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia.

Original languageEnglish (US)
Pages (from-to)1775-1783
Number of pages9
JournalAIDS
Volume29
Issue number14
DOIs
StatePublished - 2015

Fingerprint

Ritonavir
Carotid Intima-Media Thickness
Randomized Controlled Trials
Tenofovir
Therapeutics
Bilirubin
Linear Models
Cardiovascular Diseases
HIV
Hyperbilirubinemia
Protease Inhibitors
Carotid Arteries
HIV Infections
HIV-1
Ultrasonography
Diabetes Mellitus
Triglycerides
Outcome Assessment (Health Care)
RNA
Confidence Intervals

Keywords

  • Antiretroviral therapy
  • Atherosclerosis
  • Cardiovascular disease
  • Carotid arteries
  • HIV

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Stein, J. H., Ribaudo, H. J., Hodis, H. N., Brown, T. T., Tran, T. T. T., Yan, M., ... Currier, J. S. (2015). A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness. AIDS, 29(14), 1775-1783. https://doi.org/10.1097/QAD.0000000000000762

A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness. / Stein, James H.; Ribaudo, Heather J.; Hodis, Howard N.; Brown, Todd T; Tran, Thuy Tien T; Yan, Mingzhu; Brodell, Elizabeth Lauer; Kelesidis, Theodore; McComsey, Grace A.; Dube, Michael P.; Murphy, Robert L.; Currier, Judith S.

In: AIDS, Vol. 29, No. 14, 2015, p. 1775-1783.

Research output: Contribution to journalArticle

Stein, JH, Ribaudo, HJ, Hodis, HN, Brown, TT, Tran, TTT, Yan, M, Brodell, EL, Kelesidis, T, McComsey, GA, Dube, MP, Murphy, RL & Currier, JS 2015, 'A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness', AIDS, vol. 29, no. 14, pp. 1775-1783. https://doi.org/10.1097/QAD.0000000000000762
Stein, James H. ; Ribaudo, Heather J. ; Hodis, Howard N. ; Brown, Todd T ; Tran, Thuy Tien T ; Yan, Mingzhu ; Brodell, Elizabeth Lauer ; Kelesidis, Theodore ; McComsey, Grace A. ; Dube, Michael P. ; Murphy, Robert L. ; Currier, Judith S. / A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness. In: AIDS. 2015 ; Vol. 29, No. 14. pp. 1775-1783.
@article{9c42fdbf47dc4521963c534fc826c9bf,
title = "A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness",
abstract = "Objective: This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima-media thickness (IMT) over 3 years. Design: Randomized clinical trial. Setting: Multicenter (26 institutions). Patients: ART-naive HIV-infected individuals (n = 328) without known cardiovascular disease or diabetes mellitus. Intervention: Random assignment to tenofovir/emtricitabine along with atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). Main outcome measures: Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression. Results: HIV-1 RNA suppression rates were high in all arms (>85{\%}) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95{\%} confidence interval (5.6, 10.8)(Jim/year] than DRV/r [12.9 (10.3, 15.5)μum/year, P=0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2)μm/year, P=0.15 vs. ATV/r; P=0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates. Conclusion: In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia.",
keywords = "Antiretroviral therapy, Atherosclerosis, Cardiovascular disease, Carotid arteries, HIV",
author = "Stein, {James H.} and Ribaudo, {Heather J.} and Hodis, {Howard N.} and Brown, {Todd T} and Tran, {Thuy Tien T} and Mingzhu Yan and Brodell, {Elizabeth Lauer} and Theodore Kelesidis and McComsey, {Grace A.} and Dube, {Michael P.} and Murphy, {Robert L.} and Currier, {Judith S.}",
year = "2015",
doi = "10.1097/QAD.0000000000000762",
language = "English (US)",
volume = "29",
pages = "1775--1783",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "14",

}

TY - JOUR

T1 - A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness

AU - Stein, James H.

AU - Ribaudo, Heather J.

AU - Hodis, Howard N.

AU - Brown, Todd T

AU - Tran, Thuy Tien T

AU - Yan, Mingzhu

AU - Brodell, Elizabeth Lauer

AU - Kelesidis, Theodore

AU - McComsey, Grace A.

AU - Dube, Michael P.

AU - Murphy, Robert L.

AU - Currier, Judith S.

PY - 2015

Y1 - 2015

N2 - Objective: This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima-media thickness (IMT) over 3 years. Design: Randomized clinical trial. Setting: Multicenter (26 institutions). Patients: ART-naive HIV-infected individuals (n = 328) without known cardiovascular disease or diabetes mellitus. Intervention: Random assignment to tenofovir/emtricitabine along with atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). Main outcome measures: Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression. Results: HIV-1 RNA suppression rates were high in all arms (>85%) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95% confidence interval (5.6, 10.8)(Jim/year] than DRV/r [12.9 (10.3, 15.5)μum/year, P=0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2)μm/year, P=0.15 vs. ATV/r; P=0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates. Conclusion: In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia.

AB - Objective: This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima-media thickness (IMT) over 3 years. Design: Randomized clinical trial. Setting: Multicenter (26 institutions). Patients: ART-naive HIV-infected individuals (n = 328) without known cardiovascular disease or diabetes mellitus. Intervention: Random assignment to tenofovir/emtricitabine along with atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). Main outcome measures: Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression. Results: HIV-1 RNA suppression rates were high in all arms (>85%) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95% confidence interval (5.6, 10.8)(Jim/year] than DRV/r [12.9 (10.3, 15.5)μum/year, P=0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2)μm/year, P=0.15 vs. ATV/r; P=0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates. Conclusion: In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia.

KW - Antiretroviral therapy

KW - Atherosclerosis

KW - Cardiovascular disease

KW - Carotid arteries

KW - HIV

UR - http://www.scopus.com/inward/record.url?scp=84988694006&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84988694006&partnerID=8YFLogxK

U2 - 10.1097/QAD.0000000000000762

DO - 10.1097/QAD.0000000000000762

M3 - Article

C2 - 26372383

AN - SCOPUS:84988694006

VL - 29

SP - 1775

EP - 1783

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 14

ER -