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. 2016 Jul 1;1(4):474-80.
doi: 10.1001/jamacardio.2016.0846.

Effects of Antiretroviral Therapy on Immune Function and Arterial Inflammation in Treatment-Naive Patients With Human Immunodeficiency Virus Infection

Markella V Zanni  1 , Mabel Toribio  1 , Gregory K Robbins  2 , Tricia H Burdo  3 , Michael T Lu  4 , Amorina E Ishai  4 , Meghan N Feldpausch  1 , Amanda Martin  1 , Kathy Melbourne  5 , Virginia A Triant  6 , Sujit Suchindran  2 , Hang Lee  7 , Udo Hoffmann  4 , Kenneth C Williams  3 , Ahmed Tawakol  4 , Steven K Grinspoon  1
Affiliations

Effects of Antiretroviral Therapy on Immune Function and Arterial Inflammation in Treatment-Naive Patients With Human Immunodeficiency Virus Infection

Markella V Zanni et al. JAMA Cardiol. .

Abstract

Importance: 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.

Objective: To determine the effects of newly initiated ART on arterial inflammation and other immune/inflammatory indices in ART-naive patients with HIV infection.

Design, setting, participants: 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.

Interventions: Combined ART in the HIV-infected cohort.

Main outcomes and measures: The primary outcome was change in aortic target-background ratio (TBR) on [18F]-FDG-PET with combined ART in the HIV-infected group.

Results: 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.

Conclusions and relevance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr. Zanni reported participating in a scientific advisory board meeting for Roche Diagnostics and reported receiving grant support from Gilead Sciences, both unrelated to the manuscript. Dr. Melbourne is employed by Gilead Sciences. Dr. Hoffman reported receipt of grants from HeartFlow Inc, Siemens Healthcare, Genzyme, and the American College of Radiology Imaging Network and personal fees from the American Heart Association, all unrelated to this manuscript. Dr. Williams reported serving on the scientific advisory board of Macrophage Therapeutics LLC, unrelated to the manuscript. Dr. Tawakol reported serving as a consultant for Actelion, Amgen, AstraZeneca, Carenis, and Takeda and receiving grant support from Actelion, Genentech and Takeda, all unrelated to the manuscript. Dr. Grinspoon received research funding for this investigator-initiated research project from Gilead Sciences. In addition, Dr. Grinspoon reported serving as a consultant to Gilead Sciences, Theratechnologies, BMS, NovoNordisk, Merck, Navidea, Aileron, and Astra Zeneca and reported receiving grant support from Amgen, BMS, Gilead Sciences, KOWA Pharmaceuticals and Theratechnologies, all unrelated to the manuscript. No other authors reported any disclosures.

Figures

Figure 1
Figure 1. Representative 18F-FDG-PET/CT Imaging of the Aorta and Axillary Lymph Nodes in a Treatment-Naïve HIV-infected Subject Before and After E/C/F/TDF Therapy
Arrows depict right and left axillary lymph nodes. Ao = aorta. LN = lymph node.
Figure 2
Figure 2. Effects of E/C/F/TDF Therapy on 18F-FDG-PET/CT Outcomes Among ART-Naïve HIV-infected Subjects
Top row represents data as median (IQR). Bottom row displays individual data points before and after ART. Bilateral axillary lymph node TBR decreased significantly (P=0.01) and aortic TBR increased significantly (P=0.04 by two-way Wilcoxon signed rank test; P=0.98 for one-way test of decrease by Wilcoxon signed rank test). Ten of the 11 subjects’ lymph node TBR decreased while 8 of the 10 subjects’ aortic TBR increased after ART. Aortic TBR data on one participant could not be utilized as significant activity in the thymus caused spillover of activity into the aorta.
See this image and copyright information in PMC

Comment in

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