Year: 2015
Type: dissertation
Abstract: HIV-1 establishes a latent infection that is inaccessible to treatment in cellular and\nanatomical reservoirs. This thesis concerns several problematic issues of HIV-1\npersistence, including ways to measure and monitor both the virus at low viral\nconcentrations and the depletion of the reservoir. Since the central nervous system\n(CNS) is a potentially important anatomical reservoir, we also explore the extent of\nneurological injury in HIV-1 disease.\nResults from a previous study indicate that the reservoir in resting memory CD4+ Tcells\nand levels of residual viremia was reduced through intravenous\nimmunoglobulin (IVIG) treatment given to patients on combination antiretroviral\ntherapy (cART). We analyzed T-cell activation markers and potential long-term\neffects of IVIG on residual viremia. We found no lasting effect on residual viremia,\nindicating that the effect of IVIG was transient. Activation markers and interleukins\nwere not correlated to levels of residual viremia.\nCorrect measurements of residual viremia and of the reservoir size are crucial in\nHIV-1 eradication trials and may have other clinical utility. The methods employed\nneed to be sensitive and subtype independent. We evaluated a modification of the\nCOBAS TaqMan HIV-1 test, version 2.0 and a polymerase chain reaction (PCR)\nassay for total HIV-1 DNA. We achieved a sensitive quantification of plasma HIV-1\nRNA that could be used to assess residual viremia. Sensitive quantification of total\nHIV-1 DNA in peripheral blood mononuclear cells was demonstrated and both\nassays were subtype independent.\nLow level viremia in patients on cART, defined as a residual viral load of 20–1000\ncopies/ml is associated with increased risk of virologic failure. We evaluated a\nmethod used for sequencing in the case of low level viremia. The method was\nsensitive and also subtype independent, a feature making it useful in clinical settings\nwhere a diversity of subtypes is present.\nHIV-1 establishes a chronic infection that also infiltrates the CNS and carries the risk\nof developing neurological symptoms. By measuring neurofilament light protein\n(NFL) and markers of inflammation in cerebrospinal fluid (CSF), we wished to\ndetermine the extent of neurological injury and neuropathogenesis in HIV-1 disease.\nWe found increased CSF NFL both in patients with neurological symptoms and in\nneuroasymptomatic patients. Treatment decreased these levels, but treated patients\nstill retained higher levels than controls, indicating either continued virus-related\ninjury or an aging-like effect of HIV-1 infection.
Author: Tomas Mellber
Institution: University of Gothenburg
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2116400355