ABSTRACT
After the introduction of antiretroviral combination therapy for the treatment of HIV infection in 1996 (highly active antiretroviral therapy = HAART, nowadays called combination antiretroviral therapy = cART), a steady decline in infection associated complications had been expected, especially with respect to central and peripheral nervous system manifestations. Until the beginning of the new millenium this hope came in fact true, but since then there has been a slow, but constant rise in the prevalence, and later on also in the incidence of directly virus-associated neurological complications in HIV infected patients. HIV-associated diseases that neurologists might see in their routine work include HIV-associated dementia (HAD) and its precursor stages, HIV-associated myelopathy, HIV-associated polyneuropathies and myopathies as well as the opportunistic brain infections and immune reconstitution phenomena (IRIS). This article describes practical diagnostic procedures according to the guidelines of the German Neurological Society and the respective therapeutic options.
Subject(s)
AIDS Dementia Complex/therapy , Antiretroviral Therapy, Highly Active , AIDS-Related Opportunistic Infections/epidemiology , Drug Interactions , HIV Infections/complications , HIV Infections/psychology , Humans , Immune Reconstitution Inflammatory Syndrome , Muscular Diseases/etiology , Polyneuropathies/etiologyABSTRACT
Central dopaminergic (DA) systems are affected during human immunodeficiency virus (HIV) infection. So far, it is believed that they degenerate with progression of HIV disease because deterioration of DA systems is evident in advanced stages of infection. In this manuscript we found that (a) DA levels are increased and DA turnover is decreased in CSF of therapy-naïve HIV patients in asymptomatic infection, (b) DA increase does not modulate the availability of DA transporters and D2-receptors, (c) DA correlates inversely with CD4+ numbers in blood. These findings show activation of central DA systems without development of adaptive responses at DA synapses in asymptomatic HIV infection. It is probable that DA deterioration in advanced stages of HIV infection may derive from increased DA availability in early infection, resulting in DA neurotoxicity. Our findings provide a clue to the synergism between DA medication or drugs of abuse and HIV infection to exacerbate and accelerate HIV neuropsychiatric disease, a central issue in the neurobiology of HIV.
Subject(s)
Dopamine/metabolism , HIV Infections/metabolism , HIV Infections/pathology , Synaptic Transmission/physiology , 3,4-Dihydroxyphenylacetic Acid/cerebrospinal fluid , Adult , Benzamides , CD4 Antigens/metabolism , Case-Control Studies , Chemokine CCL2/metabolism , Galactosephosphates/metabolism , HIV/genetics , HIV Infections/cerebrospinal fluid , HIV Infections/diagnostic imaging , HIV Infections/immunology , Homovanillic Acid/cerebrospinal fluid , Humans , Male , Middle Aged , Pyrrolidines , Tomography, Emission-Computed, Single-Photon/methods , Tropanes , Viral Load/methodsABSTRACT
After the introduction of highly active antiretroviral therapy (HAART) in the treatment of HIV (human immunodeficiency virus) infection in 1996, neurological complications of this worldwide infectious disease declined in incidence and prevalence. During the following years however, prevalence and finally also incidence, especially of HIV-associated dementia and its precursor stages, rose again. Nowadays neurologists are confronted with HIV-associated neurocognitive disorders, depression, polyneuropathies and muscle disease, opportunistic brain infections (toxoplasmosis, cryptococcosis, cytomegalovirus infection, progressive multifocal leucoencephalopathy), rising rates of neurosyphilis, and the so-called immune reconstitution syndrome which therefore are topics of this review.
Subject(s)
AIDS Dementia Complex/diagnosis , Acquired Immunodeficiency Syndrome/diagnosis , Peripheral Nervous System Diseases/diagnosis , AIDS Dementia Complex/drug therapy , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/drug therapy , Acquired Immunodeficiency Syndrome/drug therapy , Antiretroviral Therapy, Highly Active , Brain/pathology , Depressive Disorder/diagnosis , Depressive Disorder/drug therapy , Humans , Immune Reconstitution Inflammatory Syndrome/diagnosis , Immune Reconstitution Inflammatory Syndrome/drug therapy , Magnetic Resonance Imaging , Neurologic Examination , Peripheral Nervous System Diseases/drug therapyABSTRACT
As a result of improved therapeutic possibilities with highly active antiretroviral therapy (HAART), an increasing prevalence of neurological complications of the HIV infection is observed. In particular, some authors now also describe a "morphogenesis" of the HIV-1-related encephalopathy. The current state of knowledge should be taken into account in the diagnostics and therapy of HIV-1-related encephalopathy, depression, progressive multifocal leukencephalopathy and polyneuropathy.
