| 1. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
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Normalisation of cerebrospinal fluid biomarkers parallels improvement of neurological symptoms following HAART in HIV dementia--case report.
- 2006
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Ingår i: BMC infectious diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Since the introduction of HAART the incidence of HIV dementia has declined and HAART seems to improve neurocognitive function in patients with HIV dementia. Currently, HIV dementia develops mainly in patients without effective treatment, though it has also been described in patients on HAART and milder HIV-associated neuropsychological impairment is still frequent among HIV-1 infected patients regardless of HAART. Elevated cerebrospinal fluid (CSF) levels of markers of neural injury and immune activation have been found in HIV dementia, but neither of those, nor CSF HIV-1 RNA levels have been proven useful as diagnostic or prognostic pseudomarkers in HIV dementia. CASE PRESENTATION: We report a case of HIV dementia (MSK stage 3) in a 57 year old antiretroviral naïve man who was introduced on zidovudine, lamivudine and ritonavir boosted indinavir, and followed with consecutive lumbar punctures before and after two and 15 months after initiation of HAART. Improvement of neurocognitive function was paralleled by normalisation of CSF neural markers (NFL, Tau and GFAP) levels and a decline in CSF and serum neopterin and CSF and plasma HIV-1 RNA levels. CONCLUSION: The value of these CSF markers as prognostic pseudomarkers of the effect of HAART on neurocognitive impairment in HIV dementia ought to be evaluated in longitudinal studies.
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| 2. |
- Caragounis, Eva Corina, et al.
(författare)
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Comparison of HIV-1 pol and env sequences of blood, CSF, brain and spleen isolates collected ante-mortem and post-mortem
- 2008
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Ingår i: Acta Neurol Scand. - : Hindawi Limited. - 1600-0404. ; 117:2, s. 108-16
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: HIV-1 infects the central nervous system (CNS) early in the course of infection. However, it is not known to what extent the virus evolves independently within the CNS and whether the HIV-RNA in cerebrospinal fluid (CSF) reflects the viral population replicating within the brain parenchyma or the systemic infection. The aim of this study was to investigate HIV-1 evolution in the CNS and the origin of HIV-1 in CSF. MATERIALS AND METHODS: Longitudinally derived paired blood and CSF samples and post-mortem samples from CSF, brain and spleen were collected over a period of up to 63 months from three HIV-1 infected men receiving antiretroviral treatment and presenting with symptoms of AIDS dementia complex (ADC). RESULTS: Phylogenetic analyses of HIV-1 V3, reverse transcriptase (RT) and protease sequences from patient isolates suggest compartmentalization with distinct viral strains in blood, CSF and brain. We found a different pattern of RT and accessory protease mutations in the systemic infection compared to the CNS. CONCLUSIONS: We conclude that HIV-1 may to some extent evolve independently in the CNS and the viral population in CSF mainly reflects the infection in the brain parenchyma in patients with ADC. This is of importance in understanding HIV pathogenesis and can have implications on treatment of HIV-1 patients.
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| 3. |
- Abdulle, Sahra, 1970, et al.
(författare)
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Cerebrospinal fluid viral load and intrathecal immune activation in individuals infected with different HIV-1 genetic subtypes
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: HIV-1 exhibits a high degree of genetic diversity and is presently divided into 3 distinct HIV-1 genetic groups designated major (M), non-M/non-O (N) and outlier (O). Group M, which currently comprises 9 subtypes (A-D, F-H, J and K), at least 34 circulating recombinant forms (CRFs) and several unique recombinant forms (URFs) is responsible for most of the HIV-1 epidemic. Most of the current knowledge of HIV-1 central nervous system (CNS) infection is based on subtype B. However, subtypes other than subtype B account for the majority of global HIV-1 infections. Therefore, we investigated whether subtypes have any influence on cerebrospinal fluid (CSF) markers of HIV-1 CNS infection. METHODOLOGY/PRINCIPAL FINDINGS: CSF HIV-1 RNA, CSF neopterin and CSF white blood cell (WBC) count were measured in patients infected with different HIV-1 subtypes. Using multivariate regression analysis, no differences in the CSF WBC count, neopterin and viral load were found between various HIV-1 subtypes. CONCLUSIONS: We did not find any subtype-dependent differences in the markers evaluated in this study.
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| 4. |
- Abdulle, Sahra, 1970, et al.
(författare)
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CSF neurofilament protein (NFL) - a marker of active HIV-related neurodegeneration.
- 2007
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 254:8, s. 1026-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND METHODS : The light subunit of the neurofilament protein (NFL), a major structural component of myelinated axons, is a sensitive indicator of axonal injury in the central nervous system (CNS) in a variety of neurodegenerative disorders. Cerebrospinal fluid (CSF) NFL concentrations were measured by ELISA (normal < 250 ng/l) in archived samples from 210 HIV-infected patients not taking antiretroviral treatment: 55 with AIDS dementia complex (ADC), 44 with various CNS opportunistic infections/tumours (CNS OIs), 95 without neurological symptoms or signs, and 16 with primary HIV infection (PHI). The effect of highly active antiretroviral treatment (HAART) was studied by repeated CSF sampling in four of the ADC patients initiating treatment. RESULTS : CSF NFL concentrations were significantly higher in patients with ADC (median 2590 ng/l, IQR 780-7360) and CNS OIs (2315 ng/l, 985-7390 ng/l) than in neuroasymptomatic patients (<250 ng/l, <250-300) or PHI (<250 ng/l, <250-280), p < 0.001. Among patients with ADC, those with more severe disease (stage 2-4) had higher levels than those with milder disease (stage 0.5-1), p < 0.01. CSF NFL declined during HAART to the limit of detection in parallel with virological response and neurological improvement in ADC.CSF NFL concentrations were higher in neuroasymptomatic patients with lower CD4-cell strata than higher, p < 0.001. This increase was less marked than in the ADC patients and noted in 26/58 neuroasymptomatic patients with CD4 counts <200/mul compared to 1/37 with CD4-cells >/=200/mul. CONCLUSIONS : The findings of this study support the value of CSF NFL as a useful marker of ongoing CNS damage in HIV infection. Markedly elevated CSF NFL concentrations in patients without CNS OIs are associated with ADC, follow the grade of severity, and decrease after initiation of effective antiretroviral treatment. Nearly all previously suggested CSF markers of ADC relate to immune activation or HIV viral load that do not directly indicate brain injury. By contrast NFL is a sensitive marker of such injury, and should prove useful in evaluating the presence and activity of ongoing CNS injury in HIV infection.
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| 5. |
- Abdulle, Sahra, 1970, et al.
(författare)
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Effects of antiretroviral treatment on blood-brain barrier integrity and intrathecal immunoglobulin production in neuroasymptomatic HIV-1-infected patients.
- 2005
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Ingår i: HIV medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 6:3, s. 164-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the effect of antiretroviral combination therapy on blood-brain barrier (BBB) integrity and intrathecal immunoglobulin G (IgG) production. METHODS: Lumbar punctures were performed on 38 neurologically asymptomatic, treatment-naive HIV-1-infected patients prior to and during treatment at intervals of approximately 4 months, 1 year and 2 years. Albumin ratio and IgG index were analysed as markers of BBB integrity and intrathecal IgG synthesis. RESULTS: HIV-1 RNA decreased to < 50 HIV-1 RNA copies/mL in the cerebrospinal fluid (CSF) of all patients and in the plasma of all but one patient. Only 5% of patients had elevated albumin ratio values at baseline, while 56% had an elevated IgG index. There was no significant reduction of the albumin ratio or the IgG index. After 2 years of treatment all patients had normal albumin ratio values, while 41% still had increased IgG index levels. CONCLUSIONS: Up to 2 years after the initiation of treatment, the favourable impact of antiretroviral combination treatment on CSF viral load was not accompanied by a similar reduction of intrathecal IgG production. BBB function, measured as the albumin ratio, was not significantly changed in this cohort of neurologically asymptomatic HIV-1-infected patients.
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| 6. |
- Antinori, A., et al.
(författare)
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Updated research nosology for HIV-associated neurocognitive disorders
- 2007
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Ingår i: Neurology. ; 69:18, s. 1789-99
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Tidskriftsartikel (refereegranskat)abstract
- In 1991, the AIDS Task Force of the American Academy of Neurology published nomenclature and research case definitions to guide the diagnosis of neurologic manifestations of HIV-1 infection. Now, 16 years later, the National Institute of Mental Health and the National Institute of Neurological Diseases and Stroke have charged a working group to critically review the adequacy and utility of these definitional criteria and to identify aspects that require updating. This report represents a majority view, and unanimity was not reached on all points. It reviews our collective experience with HIV-associated neurocognitive disorders (HAND), particularly since the advent of highly active antiretroviral treatment, and their definitional criteria; discusses the impact of comorbidities; and suggests inclusion of the term asymptomatic neurocognitive impairment to categorize individuals with subclinical impairment. An algorithm is proposed to assist in standardized diagnostic classification of HAND.
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| 7. |
- Atlas, Ann, et al.
(författare)
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Acute psychotic symptoms in HIV-1 infected patients are associated with increased levels of kynurenic acid in cerebrospinal fluid.
- 2007
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 21:1, s. 86-91
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Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus type 1 (HIV-1) infection is associated with psychiatric complications including cognitive impairment, affective disorders, and psychosis. Previous studies have revealed a disturbed kynurenine metabolism in these patients leading to increased levels of neuroactive compounds acting at glutamatergic neurotransmission. Kynurenic acid (KYNA), one of these metabolites is a glutamate-receptor antagonist, preferentially blocking the glycine site of the N-methyl-d-aspartate (NMDA) receptor. Increased levels of brain KYNA have been suggested to induce a NMDA receptor hypofunction that is associated with psychotic symptoms. In the present study, we analyze the concentration of KYNA in the cerebrospinal fluid (CSF) from HIV-1 infected patients (n=22), including HIV-1 infected patients with psychotic symptoms (n=8) and HIV-1 infected patients without psychiatric symptoms (n=14). We found that HIV-1 infected patients had significantly higher median concentration of CSF KYNA (3.02nM) compared to healthy controls (1.17nM). Furthermore, CSF KYNA levels were significantly elevated in HIV-1 infected patients with psychotic symptoms (4.54nM) compared to patients with HIV-1 without psychiatric symptoms (2.28nM). Present results indicate that increased levels of CSF KYNA may be associated with development of psychotic symptoms in HIV-1 infected patients.
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| 8. |
- Bergroth, T., et al.
(författare)
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Difference in drug resistance patterns between minor HIV-1 populations in cerebrospinal fluid and plasma
- 2009
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Ingår i: HIV Medicine. - 1468-1293. ; 10, s. 111-115
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of the study was to determine to what extent unique drug resistance patterns appear in minor and major HIV-1 quasispecies in cerebrospinal fluid (CSF) as compared with blood. Methods Forty-four plasma and CSF samples from 13 multi-treatment-experienced patients, seven of whom provided longitudinal samples, were included in the study. The subjects had failed antiretroviral therapy including lamivudine. The reverse transcriptase (RT) gene was examined by selective real-time polymerase chain reaction (SPCR), which can detect M184I/V mutants down to 0.2% of the viral population. Results SPCR revealed differences at amino acid position 184 in the plasma/CSF populations in 12 paired samples from eight patients. One plasma sample was positive by SPCR where direct sequencing showed wild-type M184. The other 11 paired samples showed quantitative differences in the mixed populations of the mutant or wild-type M184 quasispecies. Differences in other resistance-associated mutations between plasma and CSF viruses were also found by direct sequencing. Conclusions In multi-treatment-experienced patients with therapy failure, differences in drug resistance patterns were found frequently between plasma and CSF in both minor and major viral populations. To what extent this was a true biological phenomenon remains to be established, and the clinical relevance of these findings is yet to be determined.
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| 9. |
- Bergroth, T., et al.
(författare)
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Selection of drug-resistant HIV-1 during the early phase of viral decay is uncommon in treatment-naive patients initiated on a three- or four-drug antiretroviral regimen including lamivudine
- 2009
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Ingår i: Journal of medical virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 81:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Therapy failure due to drug resistance development is a common phenomenon in HIV-infected patients. However, when the drug pressure leads to the earliest selection of drug-resistant HIV-1 populations is still unclear. In this study, the extent to which selection of the HIV-1 reverse transcriptase M184I/V mutations occur during the initial phase of viral decay in treatment-naive HIV-1 infected patients receiving antiretroviral therapy (ART) was examined. Plasma virus from three cohorts of treatment-naive patients initiating quadruple (n = 43), triple (n = 14) or dual (n = 15) lamivudine-containing ART were analyzed for M184I/V during the first 6 months of therapy using direct sequencing and a sensitive selective real-time PCR method. Among quadruple ART patients, who all were treated at primary HIV-1 infection, only one patient developed M184V after 6 weeks of therapy, having had wild-type virus at baseline. No mutations were found in chronically infected patients on triple ART. In patients on dual therapy, M184I/V mutants were found frequently. Selection of M184I/V mutants was found to be rare during the initial phase of viral decay after initiation of ART in adherent patients given a three or four-drug combination, in contrast to those receiving a less potent regimen. The results suggest that triple and quadruple lamivudine + PI or PI/r containing ART given to treatment-naive adherent patients is potent enough to prevent development of resistance during the first months of therapy.
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| 10. |
- Cinque, Paola, et al.
(författare)
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Cerebrospinal fluid interferon-gamma-inducible protein 10 (IP-10, CXCL10) in HIV-1 infection.
- 2005
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Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 0165-5728. ; 168:1-2, s. 154-63
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Tidskriftsartikel (refereegranskat)abstract
- Interferon-gamma-inducible protein (IP-10 or CXCL10) is a potent chemoattractant and has been suggested to enhance retrovirus infection and mediate neuronal injury. In order to assess this chemokine in central nervous system (CNS) HIV infection, we measured the cerebrospinal fluid (CSF) and plasma concentrations of CXCL10 by immunoassay in samples derived from 97 HIV-infected subjects across a spectrum of immunological progression and CNS complications and from 16 HIV seronegative control subjects studied at three clinical centers between 1994 and 2001. We also examined changes in the CSF and plasma CXCL10 concentrations in 30 subjects starting and three stopping antiretroviral therapy. CSF CXCL10 concentrations: (1) correlated with CSF HIV RNA and white blood cell (WBC) counts, but not with blood CXCL10, HIV RNA, or CD4 counts; (2) were increased in subjects with primary and asymptomatic HIV infections and AIDS dementia complex, but less frequently in those with more advanced infection, with or without CNS opportunistic diseases except cytomegalovirus encephalitis; (3) decreased in subjects starting antiretroviral in association with decreases in CSF and plasma HIV RNA and CSF WBCs; and (4) conversely, increased in subjects stopping treatment in parallel with CSF HIV RNA and WBCs. These results confirm that CSF CXCL10 associates closely with both CSF HIV and WBCs and suggest that this chemokine may be both a response to and contributing determinant of local infection. High CSF levels may be useful in the diagnosis of ADC in subjects with advanced immunosuppression in whom CMV encephalitis has been ruled out, though this issue requires further study.
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