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.

Author(s): Torriani FJ, Komarow L, Parker RA, Cotter BR, Currier JS, Dube MP, Fichtenbaum CJ, Gerschenson M, Mitchell CK, Murphy RL, Squires K, Stein JH, ACTG 5152s Study Team

Affiliation(s): Infection Prevention and Clinical Epidemiology Unit, University of California-San Diego, 200 West Arbor Drive, MC 8951, San Diego, California 92103, USA. ftorriani@ucsd.edu

Publication date & source: 2008-08-12, J Am Coll Cardiol., 52(7):569-76.

Publication type: Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

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.