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

doi:10.1016/j.jacc.2008.04.049

Journal of the American College of Cardiology

Volume 52, Issue 7, 12 August 2008, Pages 569-576

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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/mm³ and 4.8 log₁₀ 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 log₁₀ 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.

Key Words

antiretroviral therapy

cardiovascular disease risk

endothelial function

human immunodeficiency virus

Abbreviations and Acronyms

ART

antiretroviral therapy

CVD

cardiovascular disease

FMD

flow-mediated dilation

HIV

human immunodeficiency virus

NNRTI

non-nucleoside reverse transcriptase inhibitor

NRTI

nucleoside reverse transcriptase inhibitor

NTGMD

nitroglycerin-mediated vasodilation

protease inhibitor

Cited by (0)

: This multicenter trial was conducted by the AIDS Clinical Trials Group (ACTG) funded by the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute. Pharmaceutical support was provided by Abbott Laboratories and Bristol-Myers Squibb Company. The following additional grants were received: NIH AI069424, AI56933, and AI069428 (to Dr. Currier); NIH AI25859, HL72711, RR00750, and RR000750 (to Dr. Dubé); NIH AI069513 (to Dr. Fichtenbaum); NIH AI34853, RR16467, and MD000173 (to Dr. Gerschenson); NIH AI069471 (to Dr. Murphy); NIH AI38855 and AI068634 (to Ms. Komarow); NIH AI38855 and AI068634 (to Dr. Parker); NIH RR16176 and AI25915 (to Dr. Stein); NIH AI69432 (to Dr. Torriani); and NIH AI38558 and NIH AI068636 (to the ACTG leadership). Dr. Torriani is on the advisory board for Abbott. Dr. Currier has received research grants from Merck and Co., Tibotec, GlaxoSmithKline, Theratechnologies, and Schering-Plough; has received honoraria from Gilead, Koronnis, Achillion, and Vertex; and has been a consultant/advisory board member for Bristol-Myers Squibb, Pfizer, Merck, and Gilead. Dr. Dubé has received research grants from Abbott and Bristol-Myers Squibb and has been a consultant to GlaxoSmithKline, Tibotec, Gilead, Bristol-Myers Squibb, and Abbott. Dr. Fichtenbaum has received research grants from Abbott and Bristol-Myers Squibb; has been on the Speakers' Bureaus of Abbott, Bristol-Myers Squibb, and Gilead; and has received honoraria from Abbott, Bristol-Myers Squibb, and Gilead. Dr. Murphy has received research grants from Bristol-Myers Squibb and has been a consultant/advisory board member for Gilead and Bristol-Myers Squibb. Dr. Squires has received a research grant from Bristol-Myers Squibb; has received honoraria from Gilead Sciences, Bristol-Myers Squibb, and Abbott; and has been on the advisory board for Bristol-Myers Squibb, Gilead Sciences, and Abbott. Dr. Stein has received a research grant from Bristol-Myers Squibb and has been a consultant for Abbott. Joseph A. Vita, MD, served as Guest Editor for this article.