Differential regulation of neurotoxin in HIV clades: role of cocaine and methamphetamine

Curr HIV Res. 2012 Jul;10(5):429-34. doi: 10.2174/157016212802138742.


Studies have demonstrated that infection with HIV-1 (subtypes) clades might differentially contribute to HIV- 1-associated neuro cognitive disorder (HAND). Substance abuse and illicit drugs such as cocaine and methamphetamine (METH) are also known to play a role in neuronal impairments. Neurotoxin quinolinic acid (QUIN) and arachidonic acid (AA) metabolites are regulators of central nervous system (CNS) functions. These neurotoxins are dysregulated during HIV infection, and substance abuse exacerbates immune and neuronal dysfunctions, leading to dementia and neurocognitive impairments. Studies have demonstrated an association between HIV infection and substance abuse in terms of viral replication and disease progression in Neuro-AIDS. In this review, we briefly discuss the effect of cocaine and METH, and differential role of HIV-1 B and C induced indoleamine-2, 3-dioxygenase (IDO) and cyclooxygenase-2 (COX-2) mediated induction of neurotoxin QUIN and AA metabolites that implicate neuronal dysfunctions.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • AIDS Dementia Complex / metabolism*
  • AIDS Dementia Complex / physiopathology
  • Acquired Immunodeficiency Syndrome / metabolism*
  • Acquired Immunodeficiency Syndrome / physiopathology
  • Arachidonic Acid / metabolism
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / metabolism*
  • Central Nervous System Stimulants / pharmacology
  • Cocaine / adverse effects
  • Cocaine / metabolism*
  • Cocaine / pharmacology
  • Cyclooxygenase 2 / metabolism
  • Disease Progression
  • Female
  • HIV Envelope Protein gp120 / drug effects
  • HIV Envelope Protein gp120 / metabolism
  • HIV-1 / drug effects
  • HIV-1 / metabolism*
  • Humans
  • Male
  • Methamphetamine / adverse effects
  • Methamphetamine / metabolism*
  • Methamphetamine / pharmacology
  • Quinolinic Acid / metabolism
  • Substance-Related Disorders
  • Up-Regulation / drug effects*
  • Virus Replication / drug effects
  • tat Gene Products, Human Immunodeficiency Virus / drug effects
  • tat Gene Products, Human Immunodeficiency Virus / metabolism


  • Central Nervous System Stimulants
  • HIV Envelope Protein gp120
  • tat Gene Products, Human Immunodeficiency Virus
  • Arachidonic Acid
  • Methamphetamine
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Quinolinic Acid
  • Cocaine