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LOWER MITOCHONDRIAL DNA COPY NUMBER IS ASSOCIATED WITH HIV & PREDICTIVE OF MORTALITY
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Reported by Jules Levin
CROI 2018 March 4-7 Boston, MA
Jing Sun1, Ryan Longchamps2, DamaniA. Piggott1, Jason A. Sumpter2, ShrutiH. Mehta1, Dan E. Arking2, Gregory D. Kirk1
1Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, US
2McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, US
from Jules: OF NOTE, look at graph you will see HIV+ have worse mitochondria numbers than HIV-neg controls CD4 <500 & detectable viral load ARE ASSOCIATED with less mtDNA copies suggesting that being on HAART, undetectable viral load & high CD4 are protective.
Program Abstract:
Lower mitochondrial DNA copy number (mtDNA CN), a marker of mitochondrial depletion, reduced energy reserves, and oxidative stress, was recently found to be predictive of adverse aging outcomes and mortality in the general population. HIV infection and its treatment may impact mitochondrial function, yet little data exist on the relationship of mtDNA CN to health outcomes in HIV infected population. We examine the relationship of mtDNA CN to HIV disease markers and mortality among persons who inject drugs (PWID) with and without HIV.
mtDNA CN was measured using the qPCR of DNA isolated from buffy coats of participants of the AIDS Linked to the IntraVenous Experience(ALIVE) cohort of current and former PWID. We used the difference of cycle threshold value between the nuclear genome (RPPH1), found in 2 copies in all humans, and mt gene (ND1) as a measure of mtDNA CN, and standardized for platelet and white blood cell counts. We further categorized the mtDNA CN into quartiles, and compared the lowest quartile vs. the other 3 quartiles (high mtDNA CN). All-cause mortality was ascertained through linkage to the National Death Index from 1988 to 2015. The relationship of mtDNA CN to HIV clinical parameters was assessed using chi2 and T tests. Cox proportional hazards regression models (controlled for age, race, gender, education, HCV infection, smoking, alcohol consumption, and current IDU) were used to assess the relationship of mtDNA CN to mortality.
Of 825 participants, 41% were ≥50 years, 62% male, 86% black, 43% had less than high school education, and 59% were HIV-infected. mtDNA CN was lower among HIV+ vs. HIV- (p<0.01), had a dose-response effect by CD4+ count (HIV+ & CD4+>500: 0.034, HIV+ & CD4+ in 200-500: -0.234, HIV+ & CD4+≤200: -0.317, P=0.03), and was lower among those who were not on ART (p<0.01).
Over a median of 7.3 yrs, there were 219 deaths (26.6%). Compared to HIV- individuals with high mtDNA CN, being HIV+ with high mtDNA CN was associated with a 1.69 fold increased risk of death (95% CI: 1.16-2.47), and being HIV+ and in the lowest quartile of mtDNA CN was associated with a 2.6 fold increased risk of death (95% CI: 1.72-3.94).
mtDNA CN and HIV infection had a synergistic impact on mortality (p=0.03).
mtDNA CN is a novel biomarker strongly associated with HIV infection, particularly with advanced HIV disease, and is predictive of all-cause mortality among people living with HIV.
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