[Highly active antiretroviral therapy of neuro-AIDS. Side effects on the nervous system and interactions]. / Hochaktive antiretrovirale Therapie bei Neuro-AIDS. Nebenwirkungen auf das Nervensystem und Interaktionen.

Highly active antiretroviral therapy (HAART) has increased the mean survival time in the AIDS stage to sometimes more than 10 years. Five different groups of antiretroviral medications are known, of which integrase inhibitors and CCR5 antagonists represent the newest and most modern substances. The long AIDS survival time implies that side effects and interactions become relatively more important and must be differentiated from the symptoms of HIV itself. Side effects of HAART concern the central and peripheral nervous system and the muscles. The neurotoxicity of the components in HAART varies considerably and depends on the substance itself. Knowledge of side effects and interactions of HAART with antiepileptics, antidepressants, and analgetics are essential for the treatment of patients with neuro-AIDS.

Successful treatment of aids related PML with HAART and cidofovir.

Progressive multifocal leukoencephalopathy (PML) is a progressive demyelinating infection of the central nervous system caused by the JC virus (JCV) in an advanced state of the acquired immunodeficiency syndrome (AIDS). Currently there are still no drugs with proven clinical efficacy against JCV, though highly active antiretroviral therapy (HAART) and the associated partial immune reconstitution have a beneficial effect on the survival time of AIDS-related PML. Various case reports have described an acceptable response under treatment with cidofovir which may be of particular benefit if HAART does not result in sufficient immune reconstitution. We report a patient with AIDS-related PML who improved under combined therapy with HAART and cidofovir. This suggests that the immediate combination of both drugs further improves the outcome of AIDS-related PML.

[HIV patients with psychiatric illnesses. Treatment strategies and drug interactions]. / HIV-Patienten mit psychiatrischen Krankheiten. Behandlungsstrategien und Medikamenteninteraktionen.

Since the beginning of the endemic phase of the human immunodeficiency virus (HIV), about 60,000 humans have been infected in Germany by this retrovirus. Epidemiological data indicate approximately 2,500 new infections annually. Due to the multiagent antiviral therapy available, only about 600 cases progressed to the clinical picture of full-blown acquired immunodeficiency syndrome (AIDS) in 1999. [Robert-Koch-Institut (Berlin), http://www.rki.de] If an HIV infection or AIDS is current, a higher prevalence of psychiatric disorders in these persons can be anticipated. Psychoactive drugs and their dosages need to be chosen under several considerations and with regard to the HIV infection, since interactions between antiviral and psychotropic drugs occur frequently. The use of psychotropic drugs is often required and thus cannot be ignored. Therefore, psychiatric disorders, medical treatment strategies, interactions between psychotropic and antiretroviral drugs, and biotransformation mechanisms are discussed with regard to an underlying HIV infection.

High sensitivity detection of JC-virus DNA in postmortem brain tissue by in situ PCR.

Opportunistic infection of the central nervous system by human polyomavirus JC can cause a devastating disease, progressive multifocal leukoencephalopathy (PML). To gain new neuropathological insights into JC-virus (JCV) infection patterns in PML at the light microscopic level, the highly sensitive indirect in situ polymerase chain reaction (in situ PCR) was employed in up to 15-year old formalin-fixed and paraffin-embedded postmortem brain tissue derived from nine AIDS patients with PML. In situ PCR, in which target DNA is amplified intracellularly and detected by a specific labelled probe in morphologically intact tissue, was compared with conventional in situ hybridization (ISH). Validity was ensured by the inclusion of 13 controls. JCV detection with in situ PCR proved to be highly sensitive since in all nine brain samples the number of positive cells exceeded the ISH results by 2-3-fold. Whereas by routine staining the brain tissue of each individual patient showed regions with severe, mild or no involvement by PML, improved detection of JCV DNA by in situ PCR allowed a regrading into five different degrees of JCV infection. Significant myelin staining was observed, suggesting that cell-to-cell contact may not be the only means of virus spread but that new cells could also be infected by virus released after cell lysis. Furthermore, using in situ PCR hitherto unreported intracellular distribution patterns of JCV DNA in oligodendro- and astrocytes were observed by light microscopy.

Asymptomatic pancreatitis associated with clozapine.

Besides the well-known adverse effects of clozapine, such as granulocytopenia, tiredness and hypersalivation, acute pancreatitis is known to be a very rare complication of the drug. In the literature a total of five case reports have been published so far. We report a case of asymptomatic pancreatitis subsequent to clozapine treatment at therapeutic doses in a 38-year-old male patient with chronic paranoid-hallucinatory schizophrenia. The patient was rehospitalized after an acute exacerbation of the psychosis subsequent to an attempt to change medication on an outpatient basis. Treatment with clozapine was initiated again. During phases of progressively increasing the clozapine dose, serum levels of amylase and lipase were increased; after maintaining daily doses of clozapine of 300 mg and/or 600 mg the pancreatic enzymes normalized quickly within a few days. The patient did not report any pancreas-related complaints, nor did specific diagnostic studies produce any indicative result, only a minor thickening of the head and body of the pancreas in the ultrasound. It is assumed that the phenomenon of subclinical, asymptomatic pancreatitis during increasing dosage of clozapine occurs more often than previously supposed. The monitoring of serum amylase levels during slow increase in clozapine is recommended; if leukocytosis or eosinophilia is present, the possibility of even a subclinical and asymptomatic pancreatitis should be considered.

Neurological reactions in HIV-infected patients treated with trichosanthin.

Trichosanthin is a ribosome-inactivating protein that is being studied as a possible treatment for patients infected with human immunodeficiency virus (HIV). We report the clinical and pathological features in two patients who experienced neurological reactions to trichosanthin. Both patients were neurologically asymptomatic prior to treatment but developed coma and multifocal neurological deficits after treatment. Neuropathological examination revealed regions of severe, multifocal necrosis with histiocytic infiltrates. These reactions to trichosanthin may be mediated by soluble factors released by HIV-infected macrophages.

Progressive multifocal leukoencephalopathy in AIDS: a clinicopathologic study and review of the literature.

We reviewed the clinical, radiographic, and pathologic features of 15 patients with the acquired immune deficiency syndrome (AIDS) and progressive multifocal leukoencephalopathy (PML). Brain tissue from 10 autopsy and 6 biopsy specimens was studied using: in situ hybridization (ISH) for JC virus (JCV), immunohistochemistry for human immunodeficiency virus (HIV) p24 antigen, and electron microscopy. Thirteen patients presented with focal neurologic deficits, while 2 presented with a rapid decline in mental status. PML was commonly the initial opportunistic infection of AIDS and produced hemiparesis, dementia, dysarthria, cerebellar abnormalities, and seizures. Magnetic resonance imaging was more sensitive than computed tomography in detecting lesions, and often showed multifocal areas of PML. CD4+ T-cell counts were uniformly low (mean 84/mm3), except in 1 patient who improved on 3'-azido-3'-deoxythymidine (AZT). PML involved the cerebral hemispheres, brain stem, cerebellum, and cervical spinal cord. The distribution of brain involvement was consistent with hematogenous dissemination of the virus. In 2 brain specimens, multiple HIV-type giant cells were present within the regions involved by PML. When co-infection by HIV and papovavirus was present, PML dominated the pathological picture. ISH for JCV showed virus in the nuclei of oligodendrocytes and astrocytes. Occasionally there was staining for JCV in the cytoplasm of glial cells and in the neuropil, the latter possibly a correlate of papovavirus spread between myelin sheaths, as seen by electron microscopy. ISH demonstrated more extensive foci of PML than did routine light microscopy.