August 12, 2008

Endothelial Function in HIV-Infected Antiretroviral Naïve Subjects Before and After Starting Potent Antiretroviral Therapy: AIDS Clinical Trials Group Study 5152s

Francesca J. Torriani, M.D., Lauren Komarow, M.S., Robert A. Parker, Sc.D., Bruno R. Cotter, M.D., F.A.C.C., Judith S. Currier, M.D., Michael P. Dubé, M.D., Carl J. Fichtenbaum, M.D., Mariana Gerschenson, Ph.D., Carol K.C. Mitchell, Ph.D., Robert L. Murphy, M.D., Kathleen Squires, M.D., James H. Stein, M.D., F.A.C.C., and the ACTG 5152s Study Team

Journal of the American College of Cardiology

Objectives—This study evaluated the effects of three class-sparing antiretroviral therapy (ART) regimens on endothelial function in HIV-infected subjects participating in a randomized trial. Background—Endothelial dysfunction has been observed in patients receiving ART for human immunodeficiency virus (HIV) infection. Methods—This was a prospective, multicenter study of treatment-naïve 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. 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 RNA values were 245 cells/mm3 and 4.8 log10 copies/ml, respectively. At baseline, FMD was 3.68% (interquartile range 1.98 – 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% (−0.62 – +2.74, p=0.003) and 1.48% (−0.20 – +4.30%, p< 0.001), respectively, with similar changes in each arm (pKW>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-naïve individuals with HIV, three different ART regimens rapidly improved endothelial function. Benefits were similar for all ART regimens, appeared quickly, and persisted at 24 weeks. Condensed Abstract—Among 82 treatment-naïve HIV-infected subjects participating in a prospective, multicenter study of three class-sparing antiretroviral therapy regimens, flow-mediated dilation of the brachial artery improved after 4 (+0.74%, p=0.003) and 24 weeks (+1.48%, p< 0.001), with similar changes in each arm (pKW>0.600).

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