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J Infect Dis. 2016 Feb 1;213(3):370-8. doi: 10.1093/infdis/jiv450. Epub 2015 Sep 7.

Persistent Immune Activation and Carotid Atherosclerosis in HIV-Infected Ugandans Receiving Antiretroviral Therapy.

Author information

1
Division of Infectious Diseases Center for Global Health, Massachusetts General Hospital Harvard Medical School.
2
Center for Global Health, Massachusetts General Hospital Department of Medicine, Brigham and Women's Hospital.
3
Faculty of Medicine, Mbarara University of Science and Technology.
4
Division of Cardiology, Department of Medicine Harvard Medical School.
5
Division of Infectious Diseases Harvard Medical School.
6
Center for Global Health, Massachusetts General Hospital Harvard Medical School.
7
University of California, San Francisco.
8
Epicentre Research Base, Mbarara, Uganda.
9
Division of Infectious Diseases Center for Global Health, Massachusetts General Hospital Ragon Institute of MGH, MIT, and Harvard, Boston.
10
University of Vermont, Burlington.
11
Boston College, Chestnut Hill, Massachusetts.
12
Division of Infectious Diseases Center for Global Health, Massachusetts General Hospital Harvard Medical School Faculty of Medicine, Mbarara University of Science and Technology.

Abstract

BACKGROUND:

Human immunodeficiency virus (HIV) infection and associated immune activation predict the risk of cardiovascular disease in resource-rich areas. Less is known about these relationships in sub-Saharan Africa.

METHODS:

Beginning in 2005, we enrolled subjects in southwestern Uganda into a cohort at the time of antiretroviral therapy (ART) initiation. Multiple immune activation measures were assessed before and 6 months after ART initiation. Beginning in 2013, participants aged >40 years underwent metabolic profiling, including measurement of hemoglobin A1c and lipid levels and carotid ultrasonography. We fit regression models to identify traditional and HIV-specific correlates of common carotid intima media thickness (CCIMT).

RESULTS:

A total of 105 participants completed carotid ultrasonography, with a median completion time of 7 years following ART initiation. Age, low-density lipoprotein cholesterol level, and pre-ART HIV load were correlated with CCIMT. No association was found between CCIMT and any pre-ART biomarkers of immune activation. However, in multivariable models adjusted for cardiovascular disease risk factors, lower absolute levels of soluble CD14 and interleukin 6 and greater declines in the CD14 level and kynurenine-tryptophan ratio after 6 months of ART predicted a lower CCIMT years later (P < .01).

CONCLUSIONS:

Persistent immune activation despite ART-mediated viral suppression predicts the future atherosclerotic burden among HIV-infected Ugandans. Future work should focus on clinical correlates of these relationships, to elucidate the long-term health priorities for HIV-infected people in the region.

KEYWORDS:

HIV/AIDS; Uganda; aging; antiretroviral therapy; atherosclerosis; carotid intima media thickness; inflammation

PMID:
26347573
PMCID:
PMC4704672
DOI:
10.1093/infdis/jiv450
[Indexed for MEDLINE]
Free PMC Article

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