Molecular basis for interactions of HIV and drugs of abuse.
In certain populations around the world, the HIV pandemic is being driven by drug-abusing populations. Mounting evidence suggests that these patient populations have accelerated and more severe neurocognitive dysfunction compared with non-drug-abusing HIV-infected populations. Because most drugs of abuse are central nervous system stimulants, it stands to reason that these drugs may synergize with neurotoxic substances released during the course of HIV infection. Clinical and laboratory evidence suggests that the dopaminergic systems are most vulnerable to such combined neurotoxicity. Identifying common mechanisms of neuronal injury is critical to developing therapeutic strategies for drug-abusing HIV-infected populations. This article reviews 1) the current evidence for neurodegeneration in the setting of combined HIV infection and use of methamphetamine, cocaine, heroin or alcohol; 2) the proposed underlying mechanisms involved in this combined neurotoxicity; and 3) future directions for research. This article also suggests therapeutic approaches based on our current understanding of the neuropathogenesis of dementia due to HIV infection and drugs of abuse.
Nath
Avi
A
Department of Neurology, John Hopkins University, Baltimore, Maryland 21287, USA. anath1@jhmi.edu
Hauser
Kurt F
KF
Wojna
Valerie
V
Booze
Rosemarie M
RM
Maragos
William
W
Prendergast
Mark
M
Cass
Wayne
W
Turchan
Jadwiga T
JT
D015526:AIDS Dementia Complex / Q000503:physiopathology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D015696:Gene Products, tat / Q000633:toxicity; D015699:HIV Envelope Protein gp120 / Q000633:toxicity; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity*; D003932:Heroin / Q000633:toxicity*; D006801:Humans; D009294:Narcotics / Q000633:toxicity*; D009474:Neurons / Q000473:pathology / Q000821:virology; D051381:Rats; D019966:Substance-Related Disorders / Q000503:physiopathology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D018765:Dopamine Uptake Inhibitors; D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; D009294:Narcotics; D054322:tat Gene Products, Human Immunodeficiency Virus; D003932:Heroin; D004298:Dopamine