Subtle neuropsychological impairment and minor cognitive-motor disorder in HIV-1 infection. Neuroradiological, neurophysiological, neuroimmunological, and virological correlates.
HIV-1 infection of brain may be associated with multiple treatment targets, only the most severe of which is represented by HAD. Focusing on earlier treatment targets such as MCMD and cognitive-motor impairment in the absence of any clinical disorder (as well as neuroprotection) may prove to be of greater clinical utility in the treatment and prevention of such impairment than a focus on later-stage cognitive-motor disease, when neuronal cell death is already extensive. This may be especially important now that improvements using the protease inhibitors in triple-drug combination regimens have reduced plasma viral load to unmeasurable levels, while these drugs do not penetrate the CSF well. Currently, peripheral blood markers do not appear to be highly sensitive for central nervous system impairment, and specific CSF laboratory markers have some limited value at present-while requiring a lumbar puncture to obtain. Hence, a role for noninvasive techniques using neuroimaging exists in the clinical management of HIV-1-infected patients. To date, structural imaging techniques have proven limited in value for HIV-1-specific impairment. Several functional techniques (PET, SPECT, and MR spectroscopy) have now provided promising results for the purposes of identifying clinically significant dysfunction, relating such dysfunction to clinical neuropsychiatric symptom status, and for treatment response monitoring. Further studies are needed to examine the extent to which such imaging modalities not only parallel clinically relevant aspects of HIV-1 disease progression, but also match specific types of neuropsychologic performance deficits with potential significance for neuroanatomical localization. It is particularly important to include neurophysiological, neuroimmunological, and virological measures in studies that examine clinical neuropsychiatric status with neuroimaging techniques. In addition, the inclusion of neuropathology data, where possible, is important because demonstration of HIV-1 encephalitis cannot be equated with clinical disorder and because specific HIV-1-associated pathological changes have not yet been proven to be assessed well with neuroimaging techniques (e.g., the extent of microglial cell and macrophage activation). Also, treatment response studies are needed in conjunction with primary antiretroviral therapy regimens specifically aimed at central nervous system penetration (e.g., GW1592, GW141, and nevirapine). The results of such work will provide the data required to determine whether these promising functional neuroimaging techniques will aid in meeting the expected, imminent increase in clinical burden of this frequent complication of HIV-1 infection.
Goodkin
K
K
University of Miami School of Medicine, Florida, USA.
Wilkie
F L
FL
Concha
M
M
Asthana
D
D
Shapshak
P
P
Douyon
R
R
Fujimura
R K
RK
LoPiccolo
C
C
D015526:AIDS Dementia Complex / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000523:psychology* / Q000821:virology; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016923:Cell Death; D003072:Cognition Disorders / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000523:psychology / Q000821:virology; D018450:Disease Progression; D004338:Drug Combinations; D018792:Encephalitis, Viral / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D008262:Macrophage Activation; D009682:Magnetic Resonance Spectroscopy; D017628:Microglia / Q000821:virology; D009069:Movement Disorders / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000523:psychology / Q000821:virology; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009484:Neuropsychology; D013129:Spinal Puncture; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon; D014766:Viremia / Q000821:virology
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D015415:Biomarkers; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D018696:Neuroprotective Agents