Persistent immune activation and carotid atherosclerosis in HIV-infected Ugandans receiving antiretroviral therapy
Date
2022Author
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
BoumII, Yap
Kwon, Douglas S
Tracy, Russell P
Burdo, Tricia
Huang, Yong
Cao, Huyen
Okello, Samson
Bangsberg, David R
Hunt, Peter W
Metadata
Show full item recordAbstract
Background.
Human immunodefificiency 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 profifiling, including measurement of hemoglobin A1c and lipid levels and carotidultrasonography. We fifit regression models to identify traditional and HIV-specifific 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
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