Persistent Immune Activation and Carotid Atherosclerosis in HIV-Infected Ugandans Receiving Antiretroviral Therapy.
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.
Division of Infectious Diseases Center for Global Health, Massachusetts General Hospital Harvard Medical School.
Mark J
MJ
Siedner
Center for Global Health, Massachusetts General Hospital Department of Medicine, Brigham and Women's Hospital.
June-Ho
JH
Kim
Faculty of Medicine, Mbarara University of Science and Technology.
Ruth Sentongo
RS
Nakku
Faculty of Medicine, Mbarara University of Science and Technology.
Prossy
P
Bibangambah
Division of Cardiology, Department of Medicine Harvard Medical School.
Linda
L
Hemphill
Division of Infectious Diseases Harvard Medical School.
Virginia A
VA
Triant
Center for Global Health, Massachusetts General Hospital Harvard Medical School.
Jessica E
JE
Haberer
University of California, San Francisco.
Jeffrey N
JN
Martin
University of California, San Francisco.
A Rain
AR
Mocello
Epicentre Research Base, Mbarara, Uganda.
Yap
Y
Boum
Division of Infectious Diseases Center for Global Health, Massachusetts General Hospital Ragon Institute of MGH, MIT, and Harvard, Boston.
Douglas S
DS
Kwon
University of Vermont, Burlington.
Russell P
RP
Tracy
Boston College, Chestnut Hill, Massachusetts.
Tricia
T
Burdo
University of California, San Francisco.
Yong
Y
Huang
University of California, San Francisco.
Huyen
H
Cao
Faculty of Medicine, Mbarara University of Science and Technology.
Samson
S
Okello
Division of Infectious Diseases Center for Global Health, Massachusetts General Hospital Harvard Medical School Faculty of Medicine, Mbarara University of Science and Technology.
David R
DR
Bangsberg
University of California, San Francisco.
Peter W
PW
Hunt
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014454:Uganda / Q000453:epidemiology
D019380:Anti-HIV Agents; D015703:Antigens, CD; D015415:Biomarkers; D016207:Cytokines
HIV/AIDS; Uganda; aging; antiretroviral therapy; atherosclerosis; carotid intima media thickness; inflammation