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Association Between HIV Infection and Mitochondrial DNA Copy Number in Peripheral Blood: A Population-Based, Prospective Cohort Study

Abstract Background Low mitochondrial DNA (mtDNA) copy number (CN) is a predictor of adverse aging outcomes, and its status may be altered in human immunodeficiency virus (HIV)–infected persons. This study evaluated the cross-sectional and longitudinal change of mtDNA CN by HIV markers. Methods mtDN...

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Bibliographic Details
Published in:The Journal of infectious diseases 2019-04, Vol.219 (8), p.1285-1293
Main Authors: Sun, Jing, Longchamps, Ryan J., Piggott, Damani A., Castellani, Christina A., Sumpter, Jason A., Brown, Todd T., Mehta, Shruti H., Arking, Dan E., Kirk, Gregory D.
Format: Article
Language:English
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Summary:Abstract Background Low mitochondrial DNA (mtDNA) copy number (CN) is a predictor of adverse aging outcomes, and its status may be altered in human immunodeficiency virus (HIV)–infected persons. This study evaluated the cross-sectional and longitudinal change of mtDNA CN by HIV markers. Methods mtDNA CN was measured in the ALIVE (AIDS Linked to the Intravenous Experience) cohort of persons with a history of injecting drugs. Multivariable linear regression models controlling for demographic characteristics, behavior, and hepatitis C virus (HCV) seropositivity assessed the relationship of mtDNA CN to HIV markers (CD4+ T-cell counts, viral load, antiretroviral therapy [ART] use). Linear mixed models tested the association between HIV markers and age-related mtDNA CN trajectories. Results Among 741 individuals at baseline, 436 (59%) were infected with HIV. HIV-infected individuals who had lower CD4+ T-cell counts (P = .01), had higher viral loads (P < .01), and were not receiving ART (P < .01) had significantly lower mtDNA CNs than uninfected persons; there was no difference between participants who were uninfected and HIV-infected individuals who had well-controlled HIV levels. In longitudinal follow-up of 507 participants, from age 50 years onward, mtDNA CN declined significantly faster among HIV-infected individuals than among HIV-uninfected persons (−0.03 units of change/year vs 0.006 units of change/year; P = .04), even among infected individuals with well-controlled HIV. Conclusion Before 50 years of age, mtDNA CN is similar between HIV-infected individuals with well-controlled HIV and uninfected persons, but from age 50 onward, mtDNA CN declines significantly faster among all infected individuals than among HIV-uninfected persons. We evaluated the association between mitochondrial DNA (mtDNA) copy number (CN) and human immunodeficiency virus (HIV) among people with or at high risk of HIV acquisition. With increasing age, mtDNA CN declines faster among HIV-infected persons (including those with well-treated infection) than among HIV-uninfected persons.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiy658