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CLINICAL RESEARCH: HIV AND HEART DISEASE

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, 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 (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   PI = protease inhibitor