المؤلفون: Fehr, Jan, Glass, Tracy R., Louvel, Séverine, Hamy, François, Hirsch, Hans H., von Wyl, Viktor, Böni, Jürg, Yerly, Sabine, Bürgisser, Philippe, Cavassini, Matthias, Fux, Christoph A., Hirschel, Bernard, Vernazza, Pietro, Martinetti, Gladys, Bernasconi, Enos, Günthard, Huldrych F., Battegay, Manuel, Bucher, Heiner C., Klimkait, Thomas

المصدر: Journal of Translational Medicine; 2011, Vol. 9 Issue 1, p1-9, 9p, 4 Charts

مصطلحات موضوعية: HIV-positive persons, VIRAL replication, ANTIVIRAL agents, RNA, ANTI-infective agents

مستخلص: Background: Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. Methods: Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5log reduction). Results: Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00- 2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). Conclusions: In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success. [ABSTRACT FROM AUTHOR]

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المؤلفون: Egli, Adrian, Binet, Isabelle, Binggeli, Simone, Jäger, Clemens, Dumoulin, Alexis, Schaub, Stefan, Steiger, Juerg, Sester, Urban, Sester, Martina, Hirsch, Hans H.

المصدر: Journal of Translational Medicine; 2008, Vol. 6, Special section p1-12, 12p, 2 Diagrams, 3 Charts, 4 Graphs

مصطلحات موضوعية: IMMUNE response, T cells, CYTOMEGALOVIRUSES, VIRAL replication, KIDNEY transplantation

مصطلحات جغرافية: BASEL (Switzerland), SAINT Gall (Switzerland), SWITZERLAND

مستخلص: Background: Cytomegalovirus (CMV) seronegative recipients (R-) of kidney transplants (KT) from seropositive donors (D+) are at higher risk for CMV replication and ganciclovir(GCV)-resistance than CMV R(+). We hypothesized that low CMV-specific T-cell responses are associated with increased risk of CMV replication in R(+)-patients with D(+) or D(-) donors. Methods: We prospectively evaluated 73 consecutive KT-patients [48 R(+), 25 D(+)R(-)] undergoing routine testing for CMV replication as part of a preemptive strategy. We compared CMV-specific interferon-γ (IFN-γ) responses of CD4+CD3+ lymphocytes in peripheral blood mononuclear cells (PBMC) using three different antigen preparation (CMV-lysate, pp72- and pp65-overlapping peptide pools) using intracellular cytokine staining and flow cytometry. Results: Median CD4+ and CD8+T-cell responses to CMV-lysate, pp72- and pp65-overlapping peptide pools were lower in D(+)R(-) than in R(+)patients or in non-immunosuppressed donors. Comparing subpopulations we found that CMV-lysate favored CD4+- over CD8+-responses, whereas the reverse was observed for pp72, while pp65-CD4+- and -CD8+-responses were similar. Concurrent CMV replication in R(+)-patients was associated with significantly lower T-cell responses (pp65 median CD4+ 0.00% vs. 0.03%, p = 0.001; CD8+ 0.01% vs. 0.03%; p = 0.033). Receiver operated curve analysis associated CMV-pp65 CD4+ responses of > 0.03% in R(+)-patients with absence of concurrent (p = 0.003) and future CMV replication in the following 8 weeks (p = 0.036). GCV-resistant CMV replication occurred in 3 R(+)-patients (6.3%) with pp65- CD4+ frequencies < 0.03% (p = 0.041). Conclusion: The data suggest that pp65-specific CD4+ T-cells might be useful to identify R(+)-patients at increased risk of CMV replication. Provided further corroborating evidence, CMV-pp65 CD4+ responses above 0.03% in PBMCs of KT patients under stable immunosuppression are associated with lower risk of concurrent and future CMV replication during the following 8 weeks. [ABSTRACT FROM AUTHOR]

: Copyright of Journal of Translational Medicine is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Provenzano, Maurizio, Bracci, Laura, Wyler, Stephen, Hudolin, Tvrtko, Sais, Giovanni, Gosert, Rainer, Zajac, Paul, Palu, Giorgio, Heberer, Michael, Hirsch, Hans H., Spagnoli, Giulio C.

المصدر: Journal of Translational Medicine; 2006, Vol. 4, p1-15, 15p, 4 Charts, 7 Graphs

مصطلحات موضوعية: POLYOMAVIRUSES, VIRAL replication, TUMOR antigens, P53 protein, GENE expression, IMMUNOLOGICAL tolerance

مستخلص: Human polyomavirus BK (BKV) has been implicated in oncogenic transformation. Its ability to replicate is determined by the binding of its large tumor antigen (LTag) to products of tumorsuppressor genes regulating cell cycle, as specifically p53. We investigated CD8+ T immune responses to BKV LTag portions involved in p53 binding in HLA-A*0201+ BKV LTag experienced individuals. Peptides selected from either p53-binding region (LTag351-450 and LTag533-626) by current algorithms and capacity to bind HLA-A*0201 molecule were used to stimulate CD8+ T responses, as assessed by IFN-γ gene expression ex vivo and detected by cytotoxicity assays following in vitro culture. We observed epitope-specific immune responses in all HLA-A*0201+ BKV LTag experienced individuals tested. At least one epitope, LTag579-587; LLLIWFRPV, was naturally processed in non professional antigen presenting cells and induced cytotoxic responses with CTL precursor frequencies in the order of 1/20'000. Antigen specific CD8+ T cells were only detectable in the CD45RA+ subset, in both CCR7+ and CCR7- subpopulations. These data indicate that widespread cellular immune responses against epitopes within BKV LTagp53 binding regions exist and question their roles in immunosurveillance against tumors possibly associated with BKV infection. [ABSTRACT FROM AUTHOR]

: Copyright of Journal of Translational Medicine is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)