title: Effects of Antiretroviral Therapy on Immune Function and Arterial Inflammation in Treatment-Naive Patients With Human Immunodeficiency Virus Infection.
abstract: Individuals with human immunodeficiency virus (HIV) infection receiving combined antiretroviral therapy (ART) have an increased risk of myocardial infarction. Effects of ART on arterial inflammation among treatment-naive individuals with HIV are unknown.
  
  
  
  To determine the effects of newly initiated ART on arterial inflammation and other immune/inflammatory indices in ART-naive patients with HIV infection.
  
  
  
  Twelve treatment-naive HIV-infected individuals underwent fludeoxyglucose F 18 ([18F]-FDG) positron emission tomographic scanning for assessment of arterial inflammation, coronary computed tomographic angiography for assessment of subclinical atherosclerosis, and systemic immune and metabolic phenotyping before and 6 months after the initiation of therapy with elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (combined ART). Systemic immune and metabolic factors were also assessed in 12 prospectively recruited individuals without HIV serving as controls. The study began July 24, 2012, and was completed May 7, 2015.
  
  
  
  Combined ART in the HIV-infected cohort.
  
  
  
  The primary outcome was change in aortic target-background ratio (TBR) on [18F]-FDG-PET with combined ART in the HIV-infected group.
  
  
  
  For the 12 participants with HIV infection (mean (SD) age, 35 [11] years), combined ART suppressed viral load (mean [SD] log viral load, from 4.3 [0.6] to 1.3 [0] copies/mL; P < .001), increased the CD4+ T-cell count (median [IQR], from 461 [332-663] to 687 [533-882] cells/mm3; P < .001), and markedly reduced percentages of circulating activated CD4+ T cells (human leukocyte antigen-D related [HLA-DR]+CD38+CD4+) (from 3.7 [1.8-5.0] to 1.3 [0.3-2.0]; P = .008) and CD8+ T cells (HLA-DR+CD38+CD8+) (from 18.3 [8.1-27.0] to 4.0 [1.5-7.8]; P = .008), increased the percentage of circulating classical CD14+CD16- monocytes (from 85.8 [83.7-90.8] to 91.8 [87.5-93.2]; P = .04), and reduced levels of CXCL10 (mean [SD] log CXCL10, from 2.4 [0.4] to 2.2 [0.4] pg/mL; P = .03). With combined ART, uptake of [18F]-FDG in the axillary lymph nodes, as measured by TBR, decreased from a median (IQR) of 3.7 (1.3-7.0) at baseline to 1.4 (0.9-1.9; P = .01) at study end. In contrast, no significant decrease was seen in aortic TBR in response to combined ART (mean [SD], 1.9 [0.2]; median [IQR], 2.0 [1.8-2.1] at baseline to 2.2 [0.4]; 2.1 [1.9-2.6], respectively, at study end; P = .04 by 2-way test, P = .98 for test of decrease by 1-way test). Changes in aortic TBR during combined ART were significantly associated with changes in lipoprotein-associated phospholipase A2 (n = 10; r = 0.67; P = .03). Coronary plaque increased among 3 participants with HIV infection with baseline plaque and developed de novo in 1 participant during combined ART.
  
  
  
  Newly initiated combined ART in treatment-naive individuals with HIV infection had discordant effects to restore immune function without reducing arterial inflammation. Complementary strategies to reduce arterial inflammation among ART-treated HIV-infected individuals may be needed.
authors.affiliation: Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Markella V
authors.initials: MV
authors.lastname: Zanni
authors.affiliation: Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Mabel
authors.initials: M
authors.lastname: Toribio
authors.affiliation: Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Tricia H
authors.initials: TH
authors.lastname: Burdo
authors.affiliation: Cardiac Magnetic Resonance-Positron Emission Tomography-Computed Tomography Program and Division of Cardiology, Department of Radiology, Boston, Massachusetts.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lu
authors.affiliation: Cardiac Magnetic Resonance-Positron Emission Tomography-Computed Tomography Program and Division of Cardiology, Department of Radiology, Boston, Massachusetts.
authors.forename: Amorina E
authors.initials: AE
authors.lastname: Ishai
authors.affiliation: Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Meghan N
authors.initials: MN
authors.lastname: Feldpausch
authors.affiliation: Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Amanda
authors.initials: A
authors.lastname: Martin
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Kathy
authors.initials: K
authors.lastname: Melbourne
authors.affiliation: Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston6General Internal Medicine Division, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Triant
authors.affiliation: Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Sujit
authors.initials: S
authors.lastname: Suchindran
authors.affiliation: Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.affiliation: Cardiac Magnetic Resonance-Positron Emission Tomography-Computed Tomography Program and Division of Cardiology, Department of Radiology, Boston, Massachusetts.
authors.forename: Udo
authors.initials: U
authors.lastname: Hoffmann
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Williams
authors.affiliation: Cardiac Magnetic Resonance-Positron Emission Tomography-Computed Tomography Program and Division of Cardiology, Department of Radiology, Boston, Massachusetts.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Tawakol
authors.affiliation: Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Grinspoon
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001167:Arteritis / Q000000981:diagnostic imaging* / Q000188:drug therapy; D018791:CD4 Lymphocyte Count; D000068679:Emtricitabine / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008875:Middle Aged; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000068679:Emtricitabine