Does drug abuse influence the microglial response in AIDS and HIV encephalitis?
OBJECTIVE
To investigate the pathological evidence for a possible interaction between drugs of abuse and HIV infection in terms of microglial responses in early and late HIV/AIDS, and to discuss the possible long-term consequences of microglial activation in chronic HIV infection.


METHODS
This brain pathology study compared age and sex-matched control patients with HIV-negative intravenous drug users, and with HIV-positive drug users both in the presymptomatic stage and with AIDS. A further group of non-drug-using AIDS patients was included. All the AIDS patients had HIV encephalitis (HIVE) but no other significant HIV-associated brain pathology.


METHODS
Microglia/macrophages were identified in the grey and white matter of the frontal and temporal lobes and the thalamus, using antibodies to CD68 and MHCII. Objective quantitation was used to compare subjects in the different groups.


RESULTS
AIDS patients showed a significant increase in activated microglia/macrophages in both the grey and white matter of all areas compared with non-AIDS patients. Drug users with HIVE tended to have more activated microglia than non-drug-using comparison groups, but this difference was not found in all brain areas studied.


CONCLUSIONS
Drug misuse appears to enhance the microglial activation resulting from HIV infection in some individuals. Other factors such as the severity of HIVE, or systemic immune factors, are also likely to affect the degree of microglial activation. The implications for drug-using patients who survive long term with HIV/AIDS are discussed, particularly in relation to premature neurodegeneration.
Arango
Juan-Carlos
JC
School of Molecular and Clinical Medicine, Pathology (Neuropathology), University of Edinburgh, Edinburgh, Scotland, UK.
Simmonds
Peter
P
Brettle
Ray P
RP
Bell
Jeanne E
JE
D015526:AIDS Dementia Complex / Q000150:complications / Q000503:physiopathology*; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000503:physiopathology; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001921:Brain / Q000503:physiopathology*; D005625:Frontal Lobe / Q000503:physiopathology; D015658:HIV Infections / Q000150:complications / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D008264:Macrophages / Q000502:physiology; D017628:Microglia / Q000502:physiology*; D019966:Substance-Related Disorders / Q000150:complications / Q000503:physiopathology*; D013702:Temporal Lobe / Q000503:physiopathology; D013788:Thalamus / Q000503:physiopathology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C067980:CD68 antigen, human; D000097382:CD68 Molecule