Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

[Current events in vaccination]. / Actualités en matière de vaccination.

The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages.

[Current events in vaccination]. / Actualités en matière de vaccination.

The annual meeting of the Infectious Disease Society of America (IDSA); which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve--but for how long?--the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55%, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages.

[Comparative susceptibility evolution in Escherichia coli from urinary tract infections in outpatients and inpatients at Perpignan hospital in 2002 and 2004]. / Evolution comparée de la sensibilité de souches de Escherichia coli isolées d'infections urinaires de patients consultant aux urgences et de patients hospitalisés en 2002 et 2004 à l'hôpital de Perpignan.

The medical emergency ward makes a link between outpatients and hospitalized ones, so we can study community bacterial ecology. The antibiotic susceptibility in Escherichia coli strains isolated from urinary tract infections (UTI) of patients consulting at emergency ward of our hospital in 2002 and 2004 was determined and compared with the susceptibility of the same strains isolated from UTI of hospitalized patients on the same period. The antibiotic susceptibility was performed with Microscan (Dade Behring). All bacteria were tested against the following antimicrobial agents: amoxicilline (Amx), l'amoxicilline+clavulanic acid (AMC), nalidixic acid (NA), ciprofloxacine (Cip), cotrimoxazole (SXT), nitrofurantoin (Ft). Susceptibility in E. coli strains isolated from outpatients vary from 58 to 54% for Amx, from 88 to 83% for NA, from 96 to 89% for Cip, from 82 to 79% for SXT, from 94 to 96% for Ft and remains at 60% for AMC from 2002 to 2004. Susceptibility in E. coli strains isolated from hospitalized patients vary from 52 to 47% for Amx, 55 to 53% for AMC, from 79 to 70% for NA, from 87 to 79% for Cip, from 74 to 69% for SXT, from 93 to 92% for Ft. Susceptibility in E. coli strains isolated in the community from UTI outpatients is decreasing and it becomes worrying particularly concerning the fluoroquinolones, therefore empiric treatment of pyelonephritis by fluoroquinolones must be assessed again.

[Evaluation of three testing strategies for detection of hepatitis C in a hospital medical consultation and in an HIV testing center]. / Evaluation de trois stratégies de dépistage de l'hépatite C en consultation hospitalière de Médecine générale et dans un Centre de dépistage anonyme et gratuit du virus de l'immunodéficience humaine.

AIMS: Testing for hepatitis C virus (HCV) is recommended. The purpose of this study was to evaluate the efficacy of HCV testing in a medical consultation without an appointment and in an HIV testing center based on three testing strategies: 1997 French Consensus Conference, "Lettre de la Direction Générale de la Santé" (January 1996), and extension to other risk factors. PATIENTS AND METHODS: For 6 months a free blood test was offered to any patient with a risk factor according to the literature. RESULTS: There were 1 736 new patients at the medical consultation and 1 616 at the testing center. The patients were younger at the testing center than at the medical consultation (31.1 vs 43.3 years; P<0.001). Acceptance of screening was better at the testing center (97.8% vs 75.2%; P<0.001). There were more patients exposed to one of the risk factors at the testing center (31.2% vs 13.9%; P<0.001). Tests were more efficient at the testing center: 30 HCV positive patients/1 616 (1.86%) vs 11/1 736 (0.63%, P<0.01). Tests based on the 1997 French Consensus Conference provided detection in 27/30 (90%) of HCV positive patients at the testing center but only 4/11 (36.3%) at the medical consultation (P<0.01). CONCLUSION: Testing was effective in both places but was more efficient at the testing center. Efficacy of the testing strategies differs significantly according to the place of screening. At the testing center, screening can be restricted to patients with a history of intravenous drug use and blood transfusion. At the medical consultation, screening should be extended to other risk factors.

Determinants of outcome of compensated hepatitis C virus-related cirrhosis.

The aim of this study was to assess the incidence of decompensation (ascites, jaundice, variceal bleeding, and encephalopathy), hepatocellular carcinoma (HCC) and death or liver transplantation in patients with compensated hepatitis C virus (HCV)-related cirrhosis, taking into account the viral genotype and interferon (IFN) therapy. Between 1989 and 1994, 668 patients with no clinical evidence of decompensation were referred to our department for liver biopsy because of positivity for anti-HCV antibodies and elevated aminotransferase activity; 103 of these patients had cirrhosis. The median follow-up was 40 months. Fifty-nine patients were treated with IFN for a mean duration of 11+/-6 months; 3 (5%) had a prolonged biochemical and virological response. Baseline characteristics of IFN-treated and untreated patients were not significantly different. HCV genotypes (InnoLiPa) were predominantly 1b (48%) and 3a (20%). During follow-up, complications of cirrhosis occurred in 26 patients, HCC in 11 patients, and decompensation not related to HCC in 19 patients. Sixteen patients died, 94% of liver disease. Three patients were transplanted for liver failure. The 4-year risk of HCC was 11.5% (annual incidence 3.3%) and that of decompensation was 20%. Survival probability was 96% and 84% at 2 and 4 years, respectively. In multivariate analysis, the absence of IFN therapy was the only independent factor predictive both for HCC and decompensation. A low albumin level at entry and the absence of IFN therapy were the two independent factors predictive of death or liver transplantation. Probability of survival at 2 and 4 years was significantly different between IFN-treated and untreated patients (respectively 97% and 92% vs 95% and 63%, P < .0001). In conclusion, in patients with compensated HCV-related cirrhosis: 1) complications of cirrhosis are frequent, whatever the viral genotype; and 2) the severity of cirrhosis and the absence of IFN therapy are independently predictive of bad outcome.