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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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