Jing Sun1, Ryan J Longchamps2, Damani A Piggott1,3, Christina A Castellani2, Jason A Sumpter2, Todd T Brown4, Shruti H Mehta1, Dan E Arking2, Gregory D Kirk1,3. 1. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. 2. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland. 3. Division of Infectious Disease, Johns Hopkins School of Medicine, Baltimore, Maryland. 4. Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins School of Medicine, Baltimore, Maryland.
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.
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.
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