title: Mitochondrial DNA Haplogroups and Neurocognitive Impairment During HIV Infection.
abstract: BACKGROUND
  Neurocognitive impairment (NCI) remains an important complication in persons infected with human immunodeficiency virus (HIV). Ancestry-related mitochondrial DNA (mtDNA) haplogroups have been associated with outcomes of HIV infection and combination antiretroviral therapy (CART), and with neurodegenerative diseases. We hypothesize that mtDNA haplogroups are associated with NCI in HIV-infected adults and performed a genetic association study in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort.
  
  
  METHODS
  CHARTER is an observational study of ambulatory HIV-infected adults. Haplogroups were assigned using mtDNA sequence, and principal components were derived from ancestry-informative nuclear DNA variants. Outcomes were cross-sectional global deficit score (GDS) as a continuous measure, GDS impairment (GDS ≥ 0.50), and HIV-associated neurocognitive disorder (HAND) using international criteria. Multivariable models were adjusted for comorbidity status (incidental vs contributing), current CART, plasma HIV RNA, reading ability, and CD4 cell nadir.
  
  
  RESULTS
  Haplogroups were available from 1027 persons; median age 43 years, median CD4 nadir 178 cells/mm(3), 72% on CART, and 46% with HAND. The 102 (9.9%) persons of genetically determined admixed Hispanic ancestry had more impairment by GDS or HAND than persons of European or African ancestry (P < .001 for all). In multivariate models including persons of admixed Hispanic ancestry, those with haplogroup B had lower GDS (β = -0.34; P = .008) and less GDS impairment (odds ratio = 0.16; 95% confidence interval, .04, .63; P = .009) than other haplogroups. There were no significant haplogroup associations among persons of European or African ancestry.
  
  
  CONCLUSIONS
  In these mostly CART-treated persons, mtDNA haplogroup B was associated with less NCI among persons of genetically determined Hispanic ancestry. mtDNA variation may represent an ancestry-specific factor influencing NCI in HIV-infected persons.
authors.affiliation: Vanderbilt University, Nashville, Tennessee.
authors.forename: Todd
authors.initials: T
authors.lastname: Hulgan
authors.affiliation: Vanderbilt University, Nashville, Tennessee.
authors.forename: David C
authors.initials: DC
authors.lastname: Samuels
authors.affiliation: Vanderbilt University, Nashville, Tennessee.
authors.forename: William
authors.initials: W
authors.lastname: Bush
authors.affiliation: University of California-San Diego, California.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.affiliation: University of California-San Diego, California.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.affiliation: University of California-San Diego, California.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
authors.affiliation: University of California-San Diego, California.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Franklin
authors.affiliation: Vanderbilt University, Nashville, Tennessee.
authors.forename: Peter
authors.initials: P
authors.lastname: Straub
authors.affiliation: Vanderbilt University, Nashville, Tennessee.
authors.forename: Deborah G
authors.initials: DG
authors.lastname: Murdock
authors.affiliation: Washington University, St. Louis, Missouri.
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.affiliation: University of Washington, Seattle.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.affiliation: University of Texas Medical Branch, Galveston.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.affiliation: University of Washington, Seattle.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.affiliation: University of California-San Diego, California.
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.affiliation: University of California-San Diego, California.
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.affiliation: Cleveland Clinic Foundation/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine, Ohio.
authors.forename: Asha R
authors.initials: AR
authors.lastname: Kallianpur
mesh_terms: D015526:AIDS Dementia Complex / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D015658:HIV Infections / Q000150:complications*; D006239:Haplotypes; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial
keywords: AIDS; DNA, mitochondrial; HIV; cognitive disorders