Date Published:
2016 Mar 27

Publication Type:
Journal Article

Authors:

S.R. Var
T.R.C. Day
A. Vitomirov
D.M. Smith
V. Soontornniyomkij
D.J. Moore
C.L. Achim
S.R. Mehta
J. Pérez-Santiago

Secondary:
AIDS

Volume:
30

Pagination:
839-48

Issue:
6

PMID:
26807965

URL:
https://pubmed.ncbi.nlm.nih.gov/26807965

DOI:
10.1097/QAD.0000000000001027

Keywords:
Adult;Brain;Central Nervous System Stimulants;Cognition;Cohort Studies;DNA, Mitochondrial;External;HIV Infections;Humans;Male;Methamphetamine;Middle Aged;Mitochondria;neurocognitive disorders;Polymerase Chain Reaction;Substance-Related Disorders

Abstract:
<p>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.DESIGN: 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.</p>