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dc.contributor.authorAbdulle, Sahra 1970-en
dc.date.accessioned2008-08-11T10:31:22Z
dc.date.available2008-08-11T10:31:22Z
dc.date.issued2006en
dc.identifier.isbn91-628-6894-2en
dc.identifier.urihttp://hdl.handle.net/2077/16885
dc.description.abstractHuman immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) early in the course of infection and either directly or through opportunistic infections causes a spectrum of neurological complications. The most severe manifestation of HIV-1 CNS infection is AIDS Dementia Complex (ADC), which occurs in approximately 20% of untreated patients with AIDS. ADC is considered the result of a complex interplay between immune activation effects and viral replication in the brain, which ultimately leads to neuronal injury and death. Reliable markers to diagnose HIV-1 associated CNS injury, track disease progression, and identify patients at risk of developing ADC are lacking. Such markers would also be beneficial in evaluating the efficacy of antiretroviral treatment (ART) in the CNS, as well as to provide insights into the pathogenesis of HIV-1 CNS infection.HIV-1 elicits intrathecal cell-mediated and humoral immune activation. We found that ART effectively decreased the cerebrospinal fluid (CSF) concentrations of neopterin and beta2-microglobulin, but had little effect on the elevated IgG index. However, almost half of the patients still had slightly elevated levels of neopterin after 2 years of follow-up. Phylogenetic analyses have identified 3 distinct HIV-1 genetic groups. Group M, which is responsible for most of the global HIV-1 epidemic is further subdivided into subtypes and circulating recombinant forms (CRFs). Most of the current knowledge of HIV-1 CNS infection is based on studies of subtype B, which is predominant in the western world. However, subtypes other than subtype B are responsible for most of the epidemic outside the western world, and HIV-1 infections due to subtypes other than B are rapidly increasing across Europe. Markers of HIV-1 CNS infection such as HIV-1 RNA, neopterin, and white blood cell (WBC) count in CSF were measured and compared in patients infected with different HIV-1 subtypes. We did not find any significant subtype-specific differences in the neuromarkers evaluated in this study. Thus, subtypes do not appear to influence neuropathogenesis.Although there is no evidence of productive infection of neurons the end-result of HIV-1 CNS infection is neuronal damage and loss. We investigated the potential of CSF neurofilament (NFL), a sensitive indicator of axonal injury, as a marker of HIV-1 associated neurodegeneration. CSF NFL concentrations were higher in patients with ADC than in neuroasymptomatic patients, or patients with primary HIV-1 infection. Patients with severe ADC had higher CSF NFL levels compared to those with milder disease. CSF NFL declined with ART to the limit of detection in parallel with virological response and neurological improvement in patients suffering from ADC.Neurocognitive impairment remains a major concern in HIV-1 infection despite the success of ART. Studies on the pathogenesis, epidemiology, and the effects of ART on HIV-1 CNS infection are important to improve patient management.en
dc.subjectHIV-1en
dc.subjectcerebrospinal fluiden
dc.subjectantiretroviral therapyen
dc.subjectneopterinen
dc.subjectbeta2-microglobulinen
dc.subjectCSF HIV-1 RNAen
dc.subjectblood-brain barrieren
dc.subjectIgG indexen
dc.subjectHIV-related neurological diseasesen
dc.subjectAIDS Dementia Complexen
dc.subjectneurofilament proteinen
dc.subjectHIV-1 genetic subtypesen
dc.titleHIV-1 infection of the central nervous system. Markers of pathogenesis and antiretroviral treatment effectsen
dc.typeTexten
dc.type.svepDoctoral thesisen
dc.gup.originGöteborgs universitet/University of Gothenburgeng
dc.gup.departmentThe Sahlgrenska Academyeng
dc.gup.departmentSahlgrenska akademin, Institutionen för biomedicin, Klinisk bakteriologi och virologi, infektionssjukdomarswe
dc.gup.defenceplaceFöreläsningssalen, Infektionskliniken, Östra Sjukhuset, kl. 09.00en
dc.gup.defencedate2006-06-16en
dc.gup.dissdbid6853en
dc.gup.dissdb-fakultetSA


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