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  • 1
    In: Antiviral Therapy, SAGE Publications, Vol. 16, No. 7 ( 2011-10), p. 979-988
    Abstract: Despite a rising incidence of acute HCV in patients infected with HIV, the optimal therapeutic strategy (pegylated interferon-α [PEG-IFN-α] monotherapy or in combination with ribavirin) is still under debate. Methods A total of 23 HIV-infected patients were prospectively diagnosed with acute HCV and treated with PEG-IFN-α2a monotherapy (180 μg/week) for 24 or 48 weeks. Add-on ribavirin was allowed from week 4 of therapy onwards. There were three patients who were not included for different reasons. Blood samples were routinely drawn for viral load measurement and IL28B polymorphism analysis. Results Spontaneous viral clearance occurred in 1 (4%) patient. Nineteen patients (13 genotype 1 and 6 genotype 4) received treatment with PEG-IFN-α monotherapy (3 with add-on ribavirin) resulting in a rapid virological response (HCV RNA 〈 50 IU/ml at week 4) in 7 (37%) patients. A sustained virological response (SVR) was reached in 7 (37%) patients, whereas 9 (47%) patients were null-responders to treatment (that is, 〈 2 log 10 drop in HCV RNA at week 12 of therapy). The unfavourable G allele of the IL28B polymorphism rs8099917 was detected in 66% of the non-responders. In case of re-emergence of HCV viraemia after treatment discontinuation, sequence analysis of quasispecies confirmed an HCV relapse in 3 patients while 2 patients were re-infected by their previously non-responding partner. Conclusions PEG-IFN-α monotherapy resulted in a low SVR rate and a high percentage of null-response, whereas non-SVR was associated with a polymorphism in the IL28B gene (rs8099917).
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2011
    detail.hit.zdb_id: 2118396-X
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  • 2
    In: Antiviral Therapy, SAGE Publications, Vol. 11, No. 1 ( 2006-01), p. 105-116
    Abstract: In this study we investigated the long-term effect of highly active antiretroviral therapy (HAART) on HIV-specific CD4 + T-cell responses in comparison with virus-specific CD4 + T-cell responses against the persistent herpes viruses cytomegalovirus (CMV) and Epstein-Barr virus (EBV). To this end, HIV- and herpes virus-specific cellular immune responses were measured longitudinally in 10 seroconverters with long-term follow-up including 55 months of successful suppression of viral load by HAART. HIV- and CMV-specific CD4 + T cells producing interferon-γ (IFNγ) or interleukin-2 (IL-2) were analysed as well as proliferative capacity. EBV-specific CD4 + T cells were determined using a 12-day ex vivo assay. Initiation of HAART resulted in a transient increase of HIV-specific IL-2 + IFNγ + CD4 + T cells and, to a lesser extent, IL-2 + CD4 + T cells. Long-term HAART resulted in an increase in HIV-, CMV- and EBV-specific CD4 + T-cell proliferative capacity. The increase in HIV- and herpes-virus-specific CD4 + T-cell proliferative capacity after 55 months of HAART suggests that the improved proliferative response is not specific for HIV, but reflects a more general improvement of antiviral immune responses, which is induced by HAART.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2006
    detail.hit.zdb_id: 2118396-X
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  • 3
    In: International Journal of Antimicrobial Agents, Elsevier BV, Vol. 38, No. 6 ( 2011-12), p. 538-539
    Type of Medium: Online Resource
    ISSN: 0924-8579
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
    detail.hit.zdb_id: 2011829-6
    SSG: 15,3
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  • 4
    In: Antiviral Therapy, SAGE Publications, Vol. 16, No. 4 ( 2011-05), p. 565-575
    Abstract: Data are inconclusive whether treatment with HAART induces functional recovery of HIV-specific T-cells. Since the introduction of HAART, a marked decrease of cytomegalovirus (CMV) disease – for which untreated HIV-infected individuals are at increased risk – is observed, suggesting that this treatment influences CMV-specific T-cell immunity. Methods To study potential functional recovery of HIV-and CMV-specific T-cells, CD4 + and CD8 + T-cell responses were measured longitudinally after in vitro expansion using gag, pp65 and IE1 peptide pools, during HIV infection and after long-term HAART. Results HIV-specific T-cell function, measured by interferon (IFN)-γ production, was low after initiation of HAART. Interestingly, the cytotoxic function – measured by CD107a expression – of these T-cells temporarily increased after start of treatment, suggesting some functional recovery. The pp65-specific CD8 + T-cell responses tended to decrease during HIV infection, whereas pp65-specific CD4 + T-cell responses decreased upon treatment with HAART. Both pp65-specific CD4 + and CD8 + T-cell responses were low after initiation of HAART compared to healthy controls. By contrast, IE1-specific CD4 + T-cell responses increased during the course of HIV infection. After initiation of HAART, IE1-specific T-cell responses decreased, but IE1-specific CD8 + T-cells seemed increased compared to healthy controls. Conclusions This study suggests that HIV-infection leads to an altered CMV biology, affecting pp65- and IE1-specific T-cell responses in a different way, which is not restored by treatment with long-term HAART.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2011
    detail.hit.zdb_id: 2118396-X
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 5
    Online Resource
    Online Resource
    SAGE Publications ; 2013
    In:  Antiviral Therapy Vol. 18, No. 8 ( 2013-11), p. 1021-1025
    In: Antiviral Therapy, SAGE Publications, Vol. 18, No. 8 ( 2013-11), p. 1021-1025
    Abstract: HIV-induced CD4 + and CD8 + T-cell apoptosis decreases upon start of combination antiretroviral therapy (cART). Although in vitro evidence suggests an anti-apoptotic effect of protease inhibitors (PIs) as opposed to non-nucleoside reverse transcriptase inhibitors (NNRTIs), in vivo studies are inconclusive about effects of differential cART regimens on T-cell apoptosis. Methods Peripheral T-cell apoptosis was evaluated in a cross-sectional study including 20 patients on PI-and 19 on NNRTI-based combination antiretroviral therapy (cART), all with backbone therapy of tenofovir and emtricitabine and undetectable viral loads 6 months before inclusion. Spontaneous T-cell apoptosis was measured in freshly isolated peripheral blood mononuclear cells ( 〈 4 h after venipuncture) using annexin V, propidium iodide and staining for caspase activity and levels of the anti-apoptotic protein Bcl-2. Results The groups were comparable in general- and HIV-specific characteristics. In addition, T-cell activation was similar in both groups. We observed no difference in T-cell apoptosis as measured by annexin V, propidium iodide or caspase staining between PI- and NNRTI-treated patients. Interestingly, the level of anti-apoptotic protein Bcl-2 was higher in PI-treated than in NNRTI-treated patients. Conclusions In this cross-sectional study on HIV-infected patients, direct ex vivo spontaneous T-cell apoptosis rates are not differentially affected by NNRTI- or PI-based cART.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
    detail.hit.zdb_id: 2118396-X
    SSG: 15,3
    Location Call Number Limitation Availability
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