AIM: To evaluate virological response to telaprevir or boceprevir in combination with pegylated interferon and ribavirin and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus(...AIM: To evaluate virological response to telaprevir or boceprevir in combination with pegylated interferon and ribavirin and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus(HCV-HIV) coinfected patients in a real life setting. METHODS: Patients with HCV genotype 1-HIV coinfection followed in Nice University Hospital internal medicine and infectious diseases departments who initiated treatment including pegylated interferon and ribavirin(Peg IFN/RBV) + telaprevir or boceprevir, according to standard treatment protocols, between August 2011 and October 2013 entered this observational study. Patient data were extracted from an electronic database(Nadis®). Liver fibrosis was measured by elastometry(Fibroscan®) with the following cut-off values: F0-F1: < 7.1 k Pa, F2: 7.1-9.5 k Pa, F3: 9.5-14.5 k Pa, F4: ≥ 14.5 k Pa. The proportion of patients with sustained virological response(SVR) twelve weeks after completing treatment, frequency and type of adverse events, and NS3/4A protease inhibitor mutations were described. RESULTS: Forty-one patients were included: 13(31.7%) patients were HCV-treatment na?ve, 22(53.7%) had advanced liver fibrosis or cirrhosis(Fibroscan stage F3 and F4); none had decompensated cirrhosis or hepatocellular carcinoma; all were receiving antiretroviral treatment, consisting for most them(83%) in either a nucleoside reverse-transcriptase inhibitor/protease inhibitor or/integrase inhibitor combination; all patients had undetectable HIV-RNA. One patient was lost to follow-up. SVR was achieved by 52.5% of patients. Five patients experienced virological failure during treatment and four relapsed. Seven discontinued treatment due to adverse events. Main adverse events included severe anemia(88%) and rash(25%). NS3/4A protease mutations were analyzed at baseline and at the time of virological failure in the 9 patients experiencing non-response, breakthrough or relapse. No baseline resistance mutation could predict resistance to HCV protease inhibitor-based treatment. CONCLUSION: Telaprevir and boceprevir retain their place among potential treatment strategies in HIVHCV coinfected patients including those with advanced compensated liver disease and who failed previous Peg IFN/RBV therapy.展开更多
AIM To describe factors associated with treatment failure and frequency of resistance-associated substitutions(RAS).METHODS Human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients starting a first...AIM To describe factors associated with treatment failure and frequency of resistance-associated substitutions(RAS).METHODS Human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients starting a first direct-acting antiviral(DAA) regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defined as:(1) non-response [HCV-RNA remained detectable during treatment, at end of treatment(EOT)]; and(2) relapse(HCVRNA suppressed at EOT but detectable thereafter). Sequencing analysis was performed to describe prevalence of drug class-specific RAS. Factors associated with failure were determined using logistic regression models.RESULTS Among 559 patients, 77% had suppressed plasma HIV-RNA < 50 copies/mL at DAA treatment initiation, 41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in 22 patients and were mainly relapses(17, 77%) then undefined failures(3, 14%) and non-responses(2, 9%). Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5 A or NS5 B RAS were detected in 10/14 patients with samples available for sequencing analysis. After adjustment for age, sex, ribavirin use, HCV genotype and treatment duration, low platelet count was the only factor significantly associated with a higher risk of failure(OR: 6.5; 95%CI: 1.8-22.6). CONCLUSION Only 3.9% HIV-HCV coinfected patients failed DAA regimens and RAS were found in 70% of those failing. Low platelet count was independently associated with virological failure.展开更多
Objectives:We report our experience of using the 65 cm large diameter GORE^(®) DrySeal Flex Introducer sheath to facilitate transcatheter implantation of the Venus P-valve in the pulmonary position.Background:Tra...Objectives:We report our experience of using the 65 cm large diameter GORE^(®) DrySeal Flex Introducer sheath to facilitate transcatheter implantation of the Venus P-valve in the pulmonary position.Background:Transcatheter implantation of pulmonary valves can be difficult due to rigidity of the valve delivery system or the anatomy of the RVOT and pulmonary artery bifurcation and the risk of iatrogenic damage to the tricuspid valve support apparatus.Using long sheaths to pass and protect the tricuspid valve may facilitate the procedure.Methods:Multi-centre registry of patients who underwent transcatheter pulmonary valve implantation of the Venus P-valve using the GORE^(®) DrySeal Flex introducer sheath to facilitate passage of the valve to the right ventricular outflow tract.Procedural success,time to valve implantation and radiation safety parameters were analyzed.These data were compared to a control group of subjects treated between July 2014 and May 2016 with the same valve but without the use of GORE^(®) DrySeal.Results:Between December 2016 and September 2018,the Venus P-valve was successfully deployed through the GORE^(®) DrySeal in 12 patients.There were no procedure-related complications.As a control group,10 subjects treated between July 2014 and May 2016 were included.Total procedure time was significantly shorter in the GORE^(®) DrySeal group compared to the control group 96±27 min vs.164±12 min(p<0.001).Total screening time was significantly shorter in the GORE^(®) DrySeal group(24±11 min)when compared with the control group(32±14 min,p<0.001).Conclusions:We describe a modification to the previously described techniques of implanting the Venus P-valve in the pulmonary position after surgical repair of congenital heart disease.In our experience,the GORE^(®) DrySeal sheath has considerably facilitated the procedure and reduced the potential risks.展开更多
文摘AIM: To evaluate virological response to telaprevir or boceprevir in combination with pegylated interferon and ribavirin and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus(HCV-HIV) coinfected patients in a real life setting. METHODS: Patients with HCV genotype 1-HIV coinfection followed in Nice University Hospital internal medicine and infectious diseases departments who initiated treatment including pegylated interferon and ribavirin(Peg IFN/RBV) + telaprevir or boceprevir, according to standard treatment protocols, between August 2011 and October 2013 entered this observational study. Patient data were extracted from an electronic database(Nadis®). Liver fibrosis was measured by elastometry(Fibroscan®) with the following cut-off values: F0-F1: < 7.1 k Pa, F2: 7.1-9.5 k Pa, F3: 9.5-14.5 k Pa, F4: ≥ 14.5 k Pa. The proportion of patients with sustained virological response(SVR) twelve weeks after completing treatment, frequency and type of adverse events, and NS3/4A protease inhibitor mutations were described. RESULTS: Forty-one patients were included: 13(31.7%) patients were HCV-treatment na?ve, 22(53.7%) had advanced liver fibrosis or cirrhosis(Fibroscan stage F3 and F4); none had decompensated cirrhosis or hepatocellular carcinoma; all were receiving antiretroviral treatment, consisting for most them(83%) in either a nucleoside reverse-transcriptase inhibitor/protease inhibitor or/integrase inhibitor combination; all patients had undetectable HIV-RNA. One patient was lost to follow-up. SVR was achieved by 52.5% of patients. Five patients experienced virological failure during treatment and four relapsed. Seven discontinued treatment due to adverse events. Main adverse events included severe anemia(88%) and rash(25%). NS3/4A protease mutations were analyzed at baseline and at the time of virological failure in the 9 patients experiencing non-response, breakthrough or relapse. No baseline resistance mutation could predict resistance to HCV protease inhibitor-based treatment. CONCLUSION: Telaprevir and boceprevir retain their place among potential treatment strategies in HIVHCV coinfected patients including those with advanced compensated liver disease and who failed previous Peg IFN/RBV therapy.
基金Supported by Inserm-ANRS(French National Institute for Health and Medical Research-ANRS/France REcherche Nord and Sud Sida-hiv Hépatites)
文摘AIM To describe factors associated with treatment failure and frequency of resistance-associated substitutions(RAS).METHODS Human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients starting a first direct-acting antiviral(DAA) regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defined as:(1) non-response [HCV-RNA remained detectable during treatment, at end of treatment(EOT)]; and(2) relapse(HCVRNA suppressed at EOT but detectable thereafter). Sequencing analysis was performed to describe prevalence of drug class-specific RAS. Factors associated with failure were determined using logistic regression models.RESULTS Among 559 patients, 77% had suppressed plasma HIV-RNA < 50 copies/mL at DAA treatment initiation, 41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in 22 patients and were mainly relapses(17, 77%) then undefined failures(3, 14%) and non-responses(2, 9%). Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5 A or NS5 B RAS were detected in 10/14 patients with samples available for sequencing analysis. After adjustment for age, sex, ribavirin use, HCV genotype and treatment duration, low platelet count was the only factor significantly associated with a higher risk of failure(OR: 6.5; 95%CI: 1.8-22.6). CONCLUSION Only 3.9% HIV-HCV coinfected patients failed DAA regimens and RAS were found in 70% of those failing. Low platelet count was independently associated with virological failure.
文摘Objectives:We report our experience of using the 65 cm large diameter GORE^(®) DrySeal Flex Introducer sheath to facilitate transcatheter implantation of the Venus P-valve in the pulmonary position.Background:Transcatheter implantation of pulmonary valves can be difficult due to rigidity of the valve delivery system or the anatomy of the RVOT and pulmonary artery bifurcation and the risk of iatrogenic damage to the tricuspid valve support apparatus.Using long sheaths to pass and protect the tricuspid valve may facilitate the procedure.Methods:Multi-centre registry of patients who underwent transcatheter pulmonary valve implantation of the Venus P-valve using the GORE^(®) DrySeal Flex introducer sheath to facilitate passage of the valve to the right ventricular outflow tract.Procedural success,time to valve implantation and radiation safety parameters were analyzed.These data were compared to a control group of subjects treated between July 2014 and May 2016 with the same valve but without the use of GORE^(®) DrySeal.Results:Between December 2016 and September 2018,the Venus P-valve was successfully deployed through the GORE^(®) DrySeal in 12 patients.There were no procedure-related complications.As a control group,10 subjects treated between July 2014 and May 2016 were included.Total procedure time was significantly shorter in the GORE^(®) DrySeal group compared to the control group 96±27 min vs.164±12 min(p<0.001).Total screening time was significantly shorter in the GORE^(®) DrySeal group(24±11 min)when compared with the control group(32±14 min,p<0.001).Conclusions:We describe a modification to the previously described techniques of implanting the Venus P-valve in the pulmonary position after surgical repair of congenital heart disease.In our experience,the GORE^(®) DrySeal sheath has considerably facilitated the procedure and reduced the potential risks.
