Pharmacotherapy of HIV dementia.
OBJECTIVE
To review the clinical presentation and management of cognitive impairment associated with central nervous system HIV type 1 (HIV-1) infection.


METHODS
A MEDLINE search pertaining to HIV-related dementia (HIV-D) and pharmacologic management was performed. Additional literature was obtained from reference lists of the identified articles.


METHODS
All clinical trials and case reports evaluating pharmacologic efficacy in terms of clinical response, cerebrospinal fluid (CSF) changes, and neuropathology were considered for inclusion. Selection was not restricted by study design because most information consists of open uncontrolled trials and case reports.


RESULTS
HIV-D is characterized by a triad of disturbances in cognition, motor performance, and behavior in adults. Children present with developmental delay, cognitive impairment, poor brain growth, and other neurologic symptoms. The exact pathophysiologic mechanisms of HIV-D are not known. Numerous pharmacologic agents (e.g., nucleoside reverse transcriptase inhibitors, pentoxifylline, nitroglycerin, memantine, nimodipine, peptide T) are under investigation for management of HIV-D. Zidovudine is the most thoroughly investigated medication, with patients developing HIV-D less frequently and showing improvement on neuropsychological, CSF, and neuropathologic evaluations. Sustained response to zidovudine lasts 6 months to 1 year and optimal response is achieved at higher, but less tolerated, dosages. HIV-D patients frequently have comorbid psychiatric disorders requiring psychopharmacologic agents and are sensitive to the adverse effects of these medications.


CONCLUSIONS
HIV-D is a devastating complication of HIV-1 infection. Zidovudine is the therapy of choice for prevention and management of cognitive impairment in symptomatic HIV-infected patients and patients with AIDS. Recommendations for other medications cannot be made secondary to lack of data. The management of HIV-D may include multiple agents as more data become available regarding combination therapy. Well-designed controlled trials are needed to evaluate the efficacy of established treatments and investigational medications in the management of HIV-D.
Melton
S T
ST
Department of Pharmacy and Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond 23298, USA.
Kirkwood
C K
CK
Ghaemi
S N
SN
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D015497:HIV-1; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine