CLINICAL RESEARCH: HIV AND HEART DISEASE
Endothelial Function in Human Immunodeficiency Virus-Infected Antiretroviral-Naive Subjects Before and After Starting Potent Antiretroviral TherapyThe ACTG (AIDS Clinical Trials Group) Study 5152s
Francesca J. Torriani, MD*,*,
Lauren Komarow, MS ,
Robert A. Parker, ScD ,
Bruno R. Cotter, MD, FACC*,
Judith S. Currier, MD ,
Michael P. Dubé, MD ,
Carl J. Fichtenbaum, MD||,
Mariana Gerschenson, PhD¶,
Carol K.C. Mitchell, PhD#,
Robert L. Murphy, MD**,
Kathleen Squires, MD ,
James H. Stein, MD, FACC# for the ACTG 5152s Study Team
* University of California–San Diego, San Diego, California
Harvard School of Public Health, Boston, Massachusetts
University of California–Los Angeles, Los Angeles, California
Indiana University School of Medicine, Indianapolis, Indiana
|| University of Cincinnati Medical Center, Cincinnati, Ohio
¶ University of Hawaii, Honolulu, Hawaii
# University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
** Northwestern University Feinberg School of Medicine, Chicago, Illinois
 University of Southern California, Los Angeles, California.
Manuscript received March 27, 2008;
accepted April 23, 2008.
* Reprint requests and correspondence: Dr. Francesca J. Torriani, University of California–San Diego Infection Prevention and Clinical Epidemiology Unit, 200 West Arbor Drive, MC 8951, San Diego, California 92103. (Email: ftorriani{at}ucsd.edu).
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 (rs = –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
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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 | | PI = protease inhibitor |
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