Actualités sur les co-infections VIH–VHC

Objectives To evaluate the incidence of HIV–HCV co-infections and analyse the outcome in co-infected patients. Epidemiology. Effects of antivirals The prevalence of the co-infection by the HCV thus varies from 10 to 14% on subjects who have sexual behaviors at risk at 80 or 90% on users of drug IV. Numerous studies showed that the infection by the HIV made worse the natural history of the infection by the HCV [J Acquir Immune Defic Syndr 6 1993 602–610; J Hepatol 28 1998 945–950]. On the other hand, the studies which endeavoured to appreciate the effect of the antiretroviral therapeutics on the natural history of the chronic hepatitis C, on the co-infected patients, are more discussed. In cohorts of big size, it was demonstrated that the hepatic mortality increased with the exposure to antiretrovirals. However, the duration of the antiretroviral treatment also reports the more important survival of the patients, which distorts credibly the figures. The effect of the infection by the HCV on the progress of the disease with HIV is more discussed. The patients infected by the HIV, in any case, have to benefit from the research for a co-infection by the viruses of hepatitis B and C (HBV and HCV). This screening must be renewed every year, in particular on the drug addicts patients or presenting behaviors at risk. Viral replication The research of a viral replication, must be implemented for any confirmed positive HCV serology. The research of the HCV RNA needs ultrasensitive techniques of molecular biology which allow a qualitative detection andor a quantification of the viral genome (viral load). The techniques of last generation of real-time PCR combine both approaches (detection and quantification). The viral load HCV is not correlated to the degree of hepatic disease and does not predict the severity of the hepatic disease, contrary to the correlation demonstrated in the infection by the HIV. On the other hand, it can be a predictive factor in the response to the treatment. The pretherapeutic check-up also includes a determination of the viral genotype because a strong involvement in the response to the treatment was clearly demonstrated. Hepatic fibrosis The hepatic fibrosis must be estimated on patients having a chronic hepatitis because it conditions the prognosis and the treatment of the hepatitis. The anatomopathological study after hepatic biopsy (DHB) remains the reference method. Recently, the development of non invasive methods of measure of the hepatic fibrosis improved the care of hepatitis C, notably the blood tests (fibrotest BioPredictive Paris, fibrometer BLS Angers) and physical measures as the impulsional elastometry (Fibroscan® Echosens) which substitutes more and more in practice to the draining hepatic biopsy. Treatment Numerous studies now validated the treatment associating interferon pegilated and ribavirine as the reference treatment on the co-infected patients HIV/HCV. This treatment involves a high virological response going from 14 to 36% in the patients infected by a genotype 1 and 2 and from 43 to 73% in the patients infected by a genotype 2 or 3. The duration of the treatment is 48 weeks. As well as usual virological factors on the mono-infected patients (genotype, viral load), the rate of CD4 is one of the best predictive factors with a good response. Many hopes go towards the new molecules in development (inhibitors of protease), inhibitors of polymerase), with promising results on the mono-infected patients. However, the toxicity of these molecules is not very well known at the moment in the co-infected patients. It is thus necessary to perform trials in this group of patient, by watching very carefully the toxicity of the therapeutic associations

Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy

AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNA-dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear. METHODS: HCV quasispecies were studied by cloning and sequencing of sequential isolates from patients infected by HCV genotype 1b. Patients were treated by IFN-alpha2b for 3 mo followed by IFN-alpha2b alone or combined IFN-R therapy for 9 additional months. Patients were categorized into two groups based on their response to the treatments: 7 with sustained virological response (SVR) (quasispecies = 150) and 3 non-responders (NR) to IFN-R (quasispecies = 106). RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispecies during therapy. Analysis of amino acids substitutions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate the two groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients. CONCLUSION: These results suggest that detailed molecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection

Correlation between the promoter basal core and precore mutations and HBsAg quantification in French blood donors infected with hepatitis B virus

International audienceHepatitis B virus (HBV) basal core promoter (BCP) and precore (PC) mutations, HBV viral load and HBV surface antigen (HBsAg) quantitation were screened to assess correlations between these HBV markers in asymptomatic chronic hepatitis B carriers in France. From January 2006 to July 2007, 200 sera were collected from patients who were discovered to be HBsAg-positive when they volunteered to give blood. Direct sequencing of precore/core gene was used to detect A1762T/G1764A mutations in the BCP and G1896A in the PC region. HBV viral load and HBsAg were quantified with two commercials assays. The prevalence of the BCP and PC mixed/mutants were 37% and 60% respectively (P = 0.0001). HBV DNA level and HBsAg titer were significantly lower in subjects harboring the mixed/mutant PC virus compared to those infected by the wild phenotype. No significant difference was observed in HBV viral loads of blood donors infected by wild or mixed/mutant BCP viruses. Mutant or mixed PC virus was associated with male gender, HBeAb-positive status and HBV/D and HBV/E genotypes. BCP mutations were associated with age, and both HBV/A-HBV/E genotypes.The genetic properties of HBV in this cohort showed that most of the blood donors had a negative HBeAg serological status and harbored the PC mutant phenotype in combination with low levels of both HBV DNA and HBsAg. As the study was conducted in healthy subjects who could be considered as asmptomatic carriers, these results suggest a possible protective effect of the G1896A mutation against severe liver lesions. J. Med. Virol. 87:529–535, 2015. © 2014 Wiley Periodicals, Inc

Flutter analysis of a morphing wing technology demonstrator : numerical simulation and wind tunnel testing

As part of a morphing wing technology project, the flutter analysis of two finite element models and the experimental results of a morphing wing demonstrator equipped with aileron are presented. The finite element models are representing a wing section situated at the tip of the wing; the first model corresponds to a traditional aluminium upper surface skin of constant thickness and the second model corresponds to a composite optimized upper surface skin for morphing capabilities. The two models were analyzed for flutter occurrence and effects on the aeroelastic behaviour of the wing were studied by replacing the aluminium upper surface skin of the wing with a specially developed composite version. The morphing wing model with composite upper surface was manufactured and fitted with three accelerometers to record the amplitudes and frequencies during tests at the subsonic wind tunnel facility at the National Research Council. The results presented showed that no aeroelastic phenomenon occurred at the speeds, angles of attack and aileron deflections studied in the wind tunnel and confirmed the prediction of the flutter analysis on the frequencies and modal displacements