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

J Am Coll Cardiol. 2008 Aug 12;52(7):569-76. doi: 10.1016/j.jacc.2008.04.049.

Abstract

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives
  • Adult
  • Alkynes
  • Anti-HIV Agents / administration & dosage*
  • Benzoxazines / administration & dosage
  • Brachial Artery / drug effects
  • Brachial Artery / physiopathology
  • CD4 Lymphocyte Count
  • Cyclopropanes
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / pathology
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / physiopathology*
  • HIV Protease Inhibitors / administration & dosage
  • HIV-1
  • Humans
  • Lamivudine / administration & dosage
  • Lopinavir
  • Male
  • Organophosphonates / administration & dosage
  • Prospective Studies
  • Pyrimidinones / administration & dosage
  • Reverse Transcriptase Inhibitors / administration & dosage*
  • Ritonavir / administration & dosage
  • Stavudine / administration & dosage
  • Tenofovir
  • Time Factors
  • Zidovudine / administration & dosage

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • HIV Protease Inhibitors
  • Organophosphonates
  • Pyrimidinones
  • Reverse Transcriptase Inhibitors
  • Lopinavir
  • Lamivudine
  • Zidovudine
  • Tenofovir
  • Stavudine
  • Adenine
  • efavirenz
  • Ritonavir

Grant support