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Randomized Controlled Trial
. 2008 Aug 12;52(7):569-76.
doi: 10.1016/j.jacc.2008.04.049.

Endothelial function in human immunodeficiency virus-infected antiretroviral-naive subjects before and after starting potent antiretroviral therapy: The ACTG (AIDS Clinical Trials Group) Study 5152s

Francesca J Torriani  1 , Lauren Komarow, Robert A Parker, Bruno R Cotter, Judith S Currier, Michael P Dubé, Carl J Fichtenbaum, Mariana Gerschenson, Carol K C Mitchell, Robert L Murphy, Kathleen Squires, James H Stein; ACTG 5152s Study Team
Affiliations
Randomized Controlled Trial

Endothelial function in human immunodeficiency virus-infected antiretroviral-naive subjects before and after starting potent antiretroviral therapy: The ACTG (AIDS Clinical Trials Group) Study 5152s

Francesca J Torriani et al. J Am Coll Cardiol. .

Abstract

Objectives: This study evaluated the effects of 3 class-sparing antiretroviral therapy (ART) regimens on endothelial function in human immunodeficiency virus (HIV)-infected subjects participating in a randomized trial.

Background: Endothelial dysfunction has been observed in patients receiving ART for HIV infection.

Methods: This was a prospective, multicenter study of treatment-naive subjects who were randomly assigned to receive a protease inhibitor-sparing regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + efavirenz, a non-nucleoside reverse transcriptase inhibitor-sparing regimen of NRTIs + lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. The NRTIs were lamivudine + stavudine, zidovudine, or tenofovir. Brachial artery flow-mediated dilation (FMD) was determined by B-mode ultrasound before starting on ART, then after 4 and 24 weeks.

Results: There were 82 subjects (median age 35 years, 91% men, 54% white). Baseline CD4 cell counts and plasma HIV ribonucleic acid (RNA) values were 245 cells/mm(3) and 4.8 log(10) copies/ml, respectively. At baseline, FMD was 3.68% (interquartile range [IQR] 1.98% to 5.51%). After 4 and 24 weeks of ART, plasma HIV RNA decreased by 2.1 and 3.0 log(10) copies/ml, respectively. FMD increased by 0.74% (IQR -0.62% to +2.74%, p = 0.003) and 1.48% (IQR -0.20% to +4.30%, p < 0.001), respectively, with similar changes in each arm (Kruskal-Wallis p value >0.600). The decrease in plasma HIV RNA at 24 weeks was associated with greater FMD (r(s) = -0.30, p = 0.017).

Conclusions: Among treatment-naive individuals with HIV, 3 different ART regimens rapidly improved endothelial function. Benefits were similar for all ART regimens, appeared quickly, and persisted at 24 weeks.

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Conflict of interest statement

Conflicts of Interest:

Francesca J. Torriani, MD – Advisory Board: Abbott

Lauren Komarow, MS – None

Robert A. Parker, ScD – None

Bruno R. Cotter, MD – None

Judith S. Currier, MD

Research Grants: Merck and Co. – Raltegravir in Lipodystrophy, Tibotec – Antiretroviral Treatment Study, GSK – Antiretroviral Treatment, Theratechnologies (3) – Lipodystrophy, Schering-Plough – Antiretroviral Treatment

Honoraria: Gilead – DSMB, Koronnis – DSMB, Achillion – DSMB, Vertex

Consultant/Advisory Board: Bristol Myers Squibb, Pfizer, Merck, Gilead

Michael P. Dube, MD

Research Grants: Abbott, Bristol-Myers Squibb

Consultant: Glaxo Smith Kline, Tibotec, Gilead, Bristol-Myers Squibb, Abbott

Carl J. Fichtenbaum, MD

Research Grants: Abbott Research Grant – unrestricted study immune reconstitution

Abbott and Bristol-Myers Squibb – grants to support CME program

Speakers’ Bureau: Abbott, Bristol-Myers Squibb, Gilead

Honoraria: Abbott, Bristol-Myers Squibb, Gilead

Mariana Gerschenson, PhD - None

Carol Mitchell, PhD - none

Robert L. Murphy, MD

Research Grant: Bristol-Myers Squibb - Antiretroviral therapy and endothelial function

Consultant/Advisory Board: Gilead, Bristol-Myers Squibb

Kathleen E. Squires, MD

Research Grant: Bristol-Myers Squibb – grant is held by Thomas Jefferson University

Honoraria: Gilead Sciences, Bristol-Myers Squibb, Abbott

Advisory Board: Bristol-Myers Squibb, Gilead Sciences, Abbott

James H. Stein, MD

Research Grant: Bristol-Myers Squibb – Antiretroviral therapy and endothelial function

Consultant: Abbott – DSMB for lipid trial, development of vitamin D analogue

Figures

Figure 1
Figure 1
Changes in Brachial Artery Flow-Mediated Vasodilation from Baseline to Week 24 Thick bar = medians Box edges = 25th and 75th percentiles Error bars = 95% confidence intervals
See this image and copyright information in PMC

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