AIDS, dementia

Activation of immunophilin receptors in the CNS is thought to be involved in certain aspects of AIDS dementia and the CNS side effects seen with the immunosupressants, FK 506 and cyclophilin. FK 506 and related compounds also have antiischemic effects. 

Brew BJ (2004) Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex. Aids 18(Suppl 1) S75-S78... 

Brew BJ, Halman M, Catalan J, Sacktor N, Price RW, Brown S, Atkinson H, Clifford DB, Simpson D, Torres G, Hall C, Power C, Marder K, Me Arthur JC, Symonds W, Romero C (2007) Factors in AIDS dementia complex trial design results and lessons from the abacavir trial. PLoS Clin Trials 2(3) el3... 

Rostasy K, Egles C, Chauhan A, Kneissl M, Bahrani P, Yiannoutsos C, Hunter DD, Nath A, Hedreen JC, Navia BA (2003) SDE-lalpha is expressed in astrocytes and neurons in the AIDS dementia complex an in vivo and in vitro study. J Neuropathol Exp Neurol 62(6) 617-626... 

Yiannoutsos CT, Ernst T, Chang L, Lee PL, Richards T, Marra CM, Meyerhoff DJ, Jarvik JG, Kolson D, Schifitto G, Ellis RJ, Swindells S, Simpson DM, Miller EN, Gonzalez RG, Navia BA (2004) Regional patterns of brain metabolites in AIDS dementia complex. Neuroimage 23(3) 928-935... 

Brengel-Pesce K, Innocenti-Francillard P, Morand P, Chanzy B, Seigneurin JM (1997) Transient infection of astrocytes with HIV-1 primary isolates derived from patients with and without AIDS dementia complex. J Neurovirol 3 449-454 Budka H, Costanzi G, Cristina S, Lechi A, Parravicini C, Trabattoni R, Vago L (1987) Brain pathology induced by infection with the human immunodeficiency virus (HIV). A histological, immunocytochemical, and electron microscopical study of 100 autopsy cases. Acta Neuropathol (Berl) 75 185-198... 

Gonzalez E, Rovin BH, Sen L, Cooke G, DhandaR, Mummidi S, KuLkami H, Bamshad MJ, TeUes V, Anderson SA, Walter EA, Stephan KT, Deucher M, Mangano A, Bologna R, Ahuja SS, Dolan MJ, Ahuja SK (2002) HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele hnked to increased monocyte infiltration of tissues and MCP-1 levels. Proc Natl Acad Sd U S A 99 13795-13800... 

While the prevalence of DSP continues to rise as patients with HIV infection live longer, the incidence of HIV-associated neuropathy may be on the decline. Schifitto et al in the Northeast AIDS Dementia (NEAD) Consortium estimated the 1-year incidence of symptomatic neuropathy in a cohort of patients on HAART at 21% (Schifitto et al. 2005), compared to an incidence of 36% in a prior cohort from the pre-HAART era (Schifitto et al. 2002). This suggests that HAART may change the natural history of HIV-associated DSP (Comblath and Hoke 2006). 

Abromson-Leeman S, Bronson R, Luo Y, Berman M, Leeman R, Leeman J, Dorf M (2004) T-ceU properties determine disease site, clinical presentation, and cellular pathology of experimental autoimmune encephalomyelitis. Am J Pathol 165 1519-1533 Adamson DC, Wildemann B, Sasaki M, Glass JD, McArthur JC, Christov VI, Dawson TM, Dawson VL (1996) Immunologic NO synthase elevation in severe AIDS dementia and induction by HIV-1 gp41. Science 274 1917-1921... 

Nath A, Jones M, Maragos W, Booze R, Mactutus C, BeU J, Hauser KF, Mattson M (2000) Neurotoxicity and dysfunction of dopamine systems associated with AIDS dementia. Psychopharmacol 14 222-227... 

Finally, AIDS dementia has parallels with cerebral ischemia or stroke and again the key mechanism appears to involve overactivation of glutamate receptors, in particular the NMDA receptor, followed by excessive influx of calcium and the generation of free radicals. 

Conant K, Garzino-Demo A, Nath A, et al. Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia. Proc Nad Acad Sci U S A 1998 95(6) 3117-3121. 

HIV-1, HIV-2 Transmission via blood, sexual intercourse responsible for ARC, AIDS dementia, etc HIV-2 W African in origin closely related to HIV-1, but antigenically distinct... 

This class of antiretrovirals may be considered the most potent therapeutic agents for HIV to date. Protease inhibitors are used in combination regimens and combinations of reverse-transcriptase inhibitors and protease inhibitors have been proven most effective to decrease viral load and prolong survival. However, the protease inhibitors generally show poor penetration into the CNS and thus have no effect on aids dementia. The present Pis available for the treatment of HIV are indinavir, ritonavir, nel-finavir, saquinavir and (fos)amprenavir, atazanavir and lopinavir (in combination with ritonavir as ritonavir improves the bioavailability of lopinavir by inhibiting its metabolism in the liver by CYP3A). 

According to the CDC, the diagnosis of AIDS constitutes certain opportunistic infections, neoplasms, encephalopathy or wasting syndrome in the presence of HIV infection. In 1993, the CDC expanded the criteria to also include CD4+ T-cell count below 200 cells/p,l in the presence of HIV infection. The most common opportunistic infections includepneumocystis carinii pneumonia, pneumonitis, toxoplasmosis, mycobacterial disease, recurrent herpes simplex virus infection and/or cytomegalovirus infection. Kaposi s sarcoma is the most common form of cancer. HIV-related nervous system diseases include acute septic meningitis, AIDS dementia complex, subacute encephalitis, HIV encephalopathy and CNS opportunistic infections and neoplasm. 

AIDS dementia EAAT1 Increased (Vallat-Decouvelaere et al.,... 

AIDS dementia Glutamate, Quinolinate NMDA (Heyes et al., 1991 New et al., 1998)... 

AIDS dementia complex Enhanced Enhanced Upregulated (Boven et al., 1999 Ahn and Aggarwal, 2005 Alvarez et al., 2005)... 

Fig. 10.3 Chemical structures of low affinity NMDA antagonists used for the treatment of AD, AD, AIDS dementia, and migrane. Memantine (a) Amantadine (b) (R,S)-N-2-(4-(3-thienyl)phenyl)-2-propanesulfonamide (LY392098) (c) and (R)-4 -[l-fluoro-l-methyl-2-(propane-2-sulphonylamino)-ethyl]-biphenyl-4-carboxylic acid methylamide (LY503430) (d)...

---