Persistent immune activation and carotid atherosclerosis in HIV-infected ugandans receiving antiretroviral therapy

Mark J. Siedner, June Ho Kim, Ruth Sentongo Nakku, Prossy Bibangambah, Linda Hemphill, Virginia A. Triant, Jessica E. Haberer, Jeffrey N. Martin, A. Rain Mocello, Yap Boum, Douglas S. Kwon, Russell P. Tracy, Tricia Burdo, Yong Huang, Huyen Cao, Samson Okello, David Bangsberg, Peter W. Hunt

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)370-378
Number of pages9
JournalJournal of Infectious Diseases
Volume213
Issue number3
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Fingerprint

Carotid Artery Diseases
HIV
Carotid Intima-Media Thickness
Therapeutics
Ultrasonography
Cardiovascular Diseases
Kynurenine
Health Priorities
Uganda
Africa South of the Sahara
Virus Diseases
Tryptophan
LDL Cholesterol
Interleukin-6
Hemoglobins
Biomarkers
Lipids

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Medicine(all)
  • Infectious Diseases

Cite this

Siedner, M. J., Kim, J. H., Nakku, R. S., Bibangambah, P., Hemphill, L., Triant, V. A., ... Hunt, P. W. (2016). Persistent immune activation and carotid atherosclerosis in HIV-infected ugandans receiving antiretroviral therapy. Journal of Infectious Diseases, 213(3), 370-378. https://doi.org/10.1093/infdis/jiv450

Persistent immune activation and carotid atherosclerosis in HIV-infected ugandans receiving antiretroviral therapy. / Siedner, Mark J.; Kim, June Ho; Nakku, Ruth Sentongo; Bibangambah, Prossy; Hemphill, Linda; Triant, Virginia A.; Haberer, Jessica E.; Martin, Jeffrey N.; Mocello, A. Rain; Boum, Yap; Kwon, Douglas S.; Tracy, Russell P.; Burdo, Tricia; Huang, Yong; Cao, Huyen; Okello, Samson; Bangsberg, David; Hunt, Peter W.

In: Journal of Infectious Diseases, Vol. 213, No. 3, 01.02.2016, p. 370-378.

Research output: Contribution to journalArticle

Siedner, MJ, Kim, JH, Nakku, RS, Bibangambah, P, Hemphill, L, Triant, VA, Haberer, JE, Martin, JN, Mocello, AR, Boum, Y, Kwon, DS, Tracy, RP, Burdo, T, Huang, Y, Cao, H, Okello, S, Bangsberg, D & Hunt, PW 2016, 'Persistent immune activation and carotid atherosclerosis in HIV-infected ugandans receiving antiretroviral therapy', Journal of Infectious Diseases, vol. 213, no. 3, pp. 370-378. https://doi.org/10.1093/infdis/jiv450
Siedner, Mark J. ; Kim, June Ho ; Nakku, Ruth Sentongo ; Bibangambah, Prossy ; Hemphill, Linda ; Triant, Virginia A. ; Haberer, Jessica E. ; Martin, Jeffrey N. ; Mocello, A. Rain ; Boum, Yap ; Kwon, Douglas S. ; Tracy, Russell P. ; Burdo, Tricia ; Huang, Yong ; Cao, Huyen ; Okello, Samson ; Bangsberg, David ; Hunt, Peter W. / Persistent immune activation and carotid atherosclerosis in HIV-infected ugandans receiving antiretroviral therapy. In: Journal of Infectious Diseases. 2016 ; Vol. 213, No. 3. pp. 370-378.
@article{3bddb59d231c42538faa7ff4495fdf6c,
title = "Persistent immune activation and carotid atherosclerosis in HIV-infected ugandans receiving antiretroviral therapy",
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 = "aging, antiretroviral therapy, atherosclerosis, carotid intima media thickness, HIV/AIDS, inflammation, Uganda",
author = "Siedner, {Mark J.} and Kim, {June Ho} and Nakku, {Ruth Sentongo} and Prossy Bibangambah and Linda Hemphill and Triant, {Virginia A.} and Haberer, {Jessica E.} and Martin, {Jeffrey N.} and Mocello, {A. Rain} and Yap Boum and Kwon, {Douglas S.} and Tracy, {Russell P.} and Tricia Burdo and Yong Huang and Huyen Cao and Samson Okello and David Bangsberg and Hunt, {Peter W.}",
year = "2016",
month = "2",
day = "1",
doi = "10.1093/infdis/jiv450",
language = "English (US)",
volume = "213",
pages = "370--378",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Persistent immune activation and carotid atherosclerosis in HIV-infected ugandans receiving antiretroviral therapy

AU - Siedner, Mark J.

AU - Kim, June Ho

AU - Nakku, Ruth Sentongo

AU - Bibangambah, Prossy

AU - Hemphill, Linda

AU - Triant, Virginia A.

AU - Haberer, Jessica E.

AU - Martin, Jeffrey N.

AU - Mocello, A. Rain

AU - Boum, Yap

AU - Kwon, Douglas S.

AU - Tracy, Russell P.

AU - Burdo, Tricia

AU - Huang, Yong

AU - Cao, Huyen

AU - Okello, Samson

AU - Bangsberg, David

AU - Hunt, Peter W.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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.

AB - 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.

KW - aging

KW - antiretroviral therapy

KW - atherosclerosis

KW - carotid intima media thickness

KW - HIV/AIDS

KW - inflammation

KW - Uganda

UR - http://www.scopus.com/inward/record.url?scp=84960375102&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960375102&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiv450

DO - 10.1093/infdis/jiv450

M3 - Article

C2 - 26347573

AN - SCOPUS:84960375102

VL - 213

SP - 370

EP - 378

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 3

ER -