Amantadine triple therapy for non-responder hepatitis C patients. Clues for controversies (ANRS HC 03 BITRI)

Maynard, Marianne; Pradat, Pierre; Bailly, François; Rozier, Frédéric; Némoz, C.; Ahmed, Si Nafa Si; Adeleine, P.; Trépo, C.; Group, and a French Multicenter

doi:10.1016/j.jhep.2005.11.038

Cited by 35 publications

(38 citation statements)

References 32 publications

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“…first-generation protease inhibitors), genotype dependence has commonly been cited as a reason not to pursue p7 as a viable drug target. This was fuelled by both the spectre of amantadine's failings in the treatment of influenza, combined with a lack of efficacy when prototypes such as amantadine were combined with IFN/ribavirin in clinical studies (Deltenre et al, 2004;Mangia et al, 2004;Maynard et al, 2006). Nevertheless, both rimantadine and the imino-sugar N-nonyl deoxynojirimycin (NN-DNJ) displayed broad genotype activity (Gottwein et al, 2011;Griffin et al, 2008;Steinmann et al, 2007b).…”

Section: Hcv P7mentioning

confidence: 99%

Viroporins: structure, function and potential as antiviral targets

Scott

Griffin

2015

Journal of General Virology

111

146

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The channel-forming activity of a family of small, hydrophobic integral membrane proteins termed 'viroporins' is essential to the life cycles of an increasingly diverse range of RNA and DNA viruses, generating significant interest in targeting these proteins for antiviral development. Viroporins vary greatly in terms of their atomic structure and can perform multiple functions during the virus life cycle, including those distinct from their role as oligomeric membrane channels. Recent progress has seen an explosion in both the identification and understanding of many such proteins encoded by highly significant pathogens, yet the prototypic M2 proton channel of influenza A virus remains the only example of a viroporin with provenance as an antiviral drug target. This review attempts to summarize our current understanding of the channel-forming functions for key members of this growing family, including recent progress in structural studies and drug discovery research, as well as novel insights into the life cycles of many viruses revealed by a requirement for viroporin activity. Ultimately, given the successes of drugs targeting ion channels in other areas of medicine, unlocking the therapeutic potential of viroporins represents a valuable goal for many of the most significant viral challenges to human and animal health.

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Section: Hcv P7mentioning

confidence: 99%

Viroporins: structure, function and potential as antiviral targets

Scott

Griffin

2015

Journal of General Virology

111

146

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“…Of the remaining 42 full-text articles, 30 were excluded because they did not meet inclusion criteria, leaving 14 fulllength papers [3][4][5][6][7][8][9][10][11][12][13][14][15][16] meeting criteria for inclusion in the meta-analysis. Finally, 6 abstracts identified by manual search [17][18][19][20][21][22], were also included, only for the evaluation of the publication bias.…”

Section: Selection Of Trialsmentioning

confidence: 99%

“…The main features of the trials included in the meta-analysis are shown in Table 2 in Appendix. Fourteen, which accounted for 3898 patients, were reported as full papers [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Among the trials, three studies did not report the number of participating centers, while all remaining studies were multicenter trials, with the number of centers ranging from 2 to 133; among these studies 8 reported data on the prevalence of patients with cirrhosis (357/1282 = 27.8%).…”

Section: Description Of the Studiesmentioning

confidence: 99%

“…The average value of BMI among the studies was 27.5 K/m 2 . The first treatment schedule was reported in five studies only [6,8,10,11,15], showing a large variability in the doses of standard IFN and ribavirin administered.…”

Section: Description Of the Studiesmentioning

confidence: 99%

“…Several studies of retreatment with pegylated IFN (PEG-IFN) plus ribavirin in patients who failed to respond to the combination of pegylated and non-pegylated IFN plus ribavirin have been published [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. The results of these studies are inconclusive or conflicting because of the relatively small samples and the differences in patient characteristics, study design combining relapsers and nonresponders, doses of IFN and ribavirin administered in the first course, and retreatment regimens.…”

Section: Introductionmentioning

confidence: 99%

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Retreatment with pegylated interferon plus ribavirin of chronic hepatitis C non-responders to interferon plus ribavirin: A meta-analysis

Cammà

Cabibbo

Bronte

et al. 2009

Journal of Hepatology

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Background/Aims: Efficacy of retreatment with pegylated interferon (PEG-IFN) plus ribavirin of non-responders to standard or pegylated IFN plus ribavirin has been assessed in various studies, but sustained virologic response (SVR) rates are variable and factors influencing efficacy and tolerability still remain incompletely defined. We aimed to focus on SVR rates and to identify factors influencing them in this meta-analysis.Methods: MEDLINE as well as a manual search were used. Studies were included if they were controlled or uncontrolled trials, if they had been published as full-length papers and if they included non-responders to standard or pegylated IFN and ribavirin therapy. Fourteen trials were included in the meta-analysis. Data on study populations, interventions, and outcomes were extracted from trials using a random-effects model. Primary outcome was the SVR rate.Results: The pooled estimate of SVR rate was 16.3% (95% Confidence Interval -95% CI, 8.3-29.6%). There was a significant heterogeneity among studies (p < 0.0001). Heterogeneity was less apparent in studies that included fewer patients with cirrhosis or overweight. By meta-regression, higher SVR rate was observed in trials with a lower prevalence of subjects with genotype 1 infection and with fewer overweight patients. The use of a 24-week retreatment stopping rule did not affect SVR rate.Conclusions: The overall modest efficacy argues against an indiscriminate retreatment with PEG-IFN and ribavirin of all non-responders. Restricting retreatment to non-overweight patients or to those with genotype 2 or 3 infection, using a 24-week retreatment stopping rule, would optimize the potential benefit with a scarce likelihood of missing a curative response. Ó

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