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

Jing Sun, Ryan J. Longchamps, Damani Arnold Piggott, Christina A. Castellani, Jason A. Sumpter, Todd T Brown, Shruti Hemendra Mehta, Dan Arking, Gregory D Kirk

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1285-1293
Number of pages9
JournalThe Journal of infectious diseases
Volume219
Issue number8
DOIs
Publication statusPublished - Apr 8 2019

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Keywords

  • aging
  • biomarker
  • HIV
  • Mitochondrial DNA copy number

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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