title: Mitochondrial injury and cognitive function in HIV infection and methamphetamine use.
abstract: OBJECTIVE
  In this work, we evaluated the association of human immunodeficiency virus (HIV) infection and methamphetamine (METH) use with mitochondrial injury in the brain and its implication on neurocognitive impairment.
  
  
  METHODS
  Mitochondria carry their genome (mtDNA) and play a critical role in cellular processes in the central nervous system. METH is commonly used in HIV-infected populations. HIV infection and METH use can cause damage to mtDNA and lead to neurocognitive morbidity. We evaluated HIV infection and METH use with mitochondrial injury in the brain.
  
  
  METHODS
  We obtained white and gray matter from Brodmann areas 7, 8, 9, 46 of the following: HIV-infected individuals with history of past METH use (HIV+METH+, n = 16), HIV-infected individuals with no history of past METH use (HIV+METH-, n = 11), and HIV-negative controls (HIV-METH-, n = 30). We used the 'common deletion', a 4977 bp mutation, as a measurement of mitochondrial injury, and quantified levels of mtDNA and 'common deletion' by droplet digital PCR, and evaluated in relation to neurocognitive functioning [Global Deficit Score (GDS)].
  
  
  RESULTS
  Levels of mtDNA and mitochondrial injury were highest in white matter of Brodmann area 46. A higher relative proportion of mtDNA carrying the 'common deletion' was associated with lower GDS (P < 0.01) in HIV+METH+ but higher GDS (P < 0.01) in HIV+METH-.
  
  
  CONCLUSIONS
  Increased mitochondrial injury was associated with worse neurocognitive function in HIV+METH- individuals. Among HIV+METH+ individuals, an opposite effect was seen.
authors.affiliation: aUniversity of California San Diego, La Jolla, California, USA bVeterans Administration San Diego Healthcare System, San Diego, California, USA. *Sanjay R. Mehta and Josué Pérez-Santiago contributed equally to the writing of this article.
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Var
authors.forename: Tyler R C
authors.initials: TR
authors.lastname: Day
authors.forename: Andrej
authors.initials: A
authors.lastname: Vitomirov
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
authors.forename: Virawudh
authors.initials: V
authors.lastname: Soontornniyomkij
authors.forename: David J
authors.initials: DJ
authors.lastname: Moore
authors.forename: Cristian L
authors.initials: CL
authors.lastname: Achim
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Mehta
authors.forename: Josué
authors.initials: J
authors.lastname: Pérez-Santiago
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects; D003071:Cognition / Q000187:drug effects*; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects*; D019965:Neurocognitive Disorders / Q000139:chemically induced*; D016133:Polymerase Chain Reaction; D019966:Substance-Related Disorders / Q000150:complications*
chemical_list: D000697:Central Nervous System Stimulants; D004272:DNA, Mitochondrial; D008694:Methamphetamine