Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study

BACKGROUND: Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia. METHODS: A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated. RESULTS: Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected. CONCLUSIONS: Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management and to promote vaccination in HIV-infected patients

Randomised controlled study in the primary healthcare sector to investigate the effectiveness and safety of auriculotherapy for the treatment of uncomplicated chronic rachialgia: a study protocol

<p>Abstract</p> <p>Background</p> <p>Uncomplicated chronic rachialgia is a highly prevalent complaint, and one for which therapeutic results are contradictory. The aim of the present study is to evaluate the effectiveness and safety of treatment with auriculopressure, in the primary healthcare sector, carried out by trained healthcare professionals via a 30-hour course.</p> <p>Methods/Design</p> <p>The design consists of a multi-centre randomized controlled trial, with placebo, with two parallel groups, and including an economic evaluation. Patients with chronic uncomplicated rachialgia, whose GP is considering referral for auriculopressure sensory stimulation, are eligible for inclusion. Sampling will be by consecutive selection, and randomised allocation to one of the two study arms will be determined using a centralised method, following a 1:1 plan (true auriculopressure; placebo auriculopressure). The implants (true and placebo) will be replaced once weekly, and the treatment will have a duration of 8 weeks. The primary outcome measure will be the change in pain intensity, measured on a visual analogue scale (VAS) of 100 mm, at 9 weeks after beginning the treatment. A follow up study will be performed at 6 months after beginning treatment. An assessment will also be made of the changes measured in the Spanish version of the McGill Pain Questionnaire, of the changes in the Lattinen test, and of the changes in quality of life (SF-12). Also planned is an analysis of cost-effectiveness and also, if necessary, a cost-benefit analysis.</p> <p>Discussion</p> <p>This study will contribute to developing evidence on the use of auriculotherapy using Semen vaccariae [wang bu liu xing] for the treatment of uncomplicated chronic rachialgia.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN01897462.</p

Curation of viral genomes: challenges, applications and the way forward

BACKGROUND: Whole genome sequence data is a step towards generating the 'parts list' of life to understand the underlying principles of Biocomplexity. Genome sequencing initiatives of human and model organisms are targeted efforts towards understanding principles of evolution with an application envisaged to improve human health. These efforts culminated in the development of dedicated resources. Whereas a large number of viral genomes have been sequenced by groups or individuals with an interest to study antigenic variation amongst strains and species. These independent efforts enabled viruses to attain the status of 'best-represented taxa' with the highest number of genomes. However, due to lack of concerted efforts, viral genomic sequences merely remained as entries in the public repositories until recently. RESULTS: VirGen is a curated resource of viral genomes and their analyses. Since its first release, it has grown both in terms of coverage of viral families and development of new modules for annotation and analysis. The current release (2.0) includes data for twenty-five families with broad host range as against eight in the first release. The taxonomic description of viruses in VirGen is in accordance with the ICTV nomenclature. A well-characterised strain is identified as a 'representative entry' for every viral species. This non-redundant dataset is used for subsequent annotation and analyses using sequenced-based Bioinformatics approaches. VirGen archives precomputed data on genome and proteome comparisons. A new data module that provides structures of viral proteins available in PDB has been incorporated recently. One of the unique features of VirGen is predicted conformational and sequential epitopes of known antigenic proteins using in-house developed algorithms, a step towards reverse vaccinology. CONCLUSION: Structured organization of genomic data facilitates use of data mining tools, which provides opportunities for knowledge discovery. One of the approaches to achieve this goal is to carry out functional annotations using comparative genomics. VirGen, a comprehensive viral genome resource that serves as an annotation and analysis pipeline has been developed for the curation of public domain viral genome data . Various steps in the curation and annotation of the genomic data and applications of the value-added derived data are substantiated with case studies

Mother-to-child transmission of HIV infection and CTL escape through HLA-A2-SLYNTVATL epitope sequence variation

Cytotoxic T lymphocytes (CTL) play a central role in containment of HIV infection. Evasion of the immune response by CTL escape is associated with progression to disease. It is therefore hypothesised that transmitted viruses encode escape mutations within epitopes that are required for successful control of viraemia. In order to test this hypothesis, escape through the dominant HLA-A2-restricted CTL epitope SLYNTVATL (p17 Gag residues 77–85 SL9) in the setting of mother-to-child-transmission (MTCT) was investigated. Initial data from two families in which the HIV-infected mother expressed HLA-A*0201 and had transmitted the virus to other family members were consistent with this hypothesis. In addition, analysis of the gag sequence phylogeny in one family demonstrated that CTL escape variants can be successfully transmitted both horizontally and vertically. To test the hypothesis further, a larger cohort of transmitting mothers (n=8) and non-transmitters (n=14) were studied. Variation within the SL9 epitope was associated with expression of HLA-A2 (P=0.04) but overall no clear link between variation from the SL9 consensus sequence and MTCT was established. However, the high level of background diversity within p17 Gag served to obscure any possible association between escape and MTCT. In conclusion, these studies highlighted the obstacles to demonstrating CTL escape arising at this particular epitope. Alternative strategies likely to be more definitive are discussed

Hepatitis B and C infection in haemodialysis patients in Libya: prevalence, incidence and risk factors

Background: Patients receiving maintenance haemodialysis (HD) are at higher risk for acquiring Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infections than the general population. Strict infection control measures are essential to prevent nosocomial transmission. We aimed to investigate the incidence and prevalence of HBV and HCV infection in the HD population of Libya as well as risk factors for infection. Methods: All adult patients receiving maintenance HD (n=2382) in Libyan dialysis centres (n=39) were studied between May 2009 and October 2010. Testing for Hepatitis B surface antigen (HBsAg) and anti-HCV antibodies was performed at initiation of dialysis and every 3–6 months thereafter. Patients who were sero-negative for HBV and HCV (n=1160) were followed up for 1 year to detect sero-conversions. Results: Participant median age was 49 years and 58% were male. 831 patients (34.9%) were sero-positive for HBV and/or HCV (anti-HCV positive 31.1%; HBsAg positive 2.6%; both positive 1.2%). Of the sero-positive patients 4.7% were known to be infected before the initiation of HD. The prevalence of HBV±HCV infection varied widely between HD centres from 0% to 75.9%. Sero-positive patients were younger, had longer time on dialysis and more previous blood transfusions. Prospective follow-up revealed an incidence of sero-conversion of 7.7% during 1 year (7.1% HCV; 0.6% HBV). Wide variation in rates of newly acquired infections was observed between dialysis centres. All new HBV cases were referred from centres already treating HBV infected patients. New HCV infections were reported in most centres but the rate of HCV sero-conversion varied widely from 1.5% to 31%. Duration of dialysis, history of previous renal transplant and history of receiving HD in another centre in Libya were significantly associated with sero-conversion. Conclusion: Patients on maintenance HD in Libya have a high incidence and prevalence of HCV infection and lower rates of HBV infection. The factors associated with HBV and HCV infection are highly suggestive of nosocomial transmission within HD units. Urgent action is required to improve infection control measures in HD centres and to reduce dependence on blood transfusions for the treatment of anaemia. Keywords: Haemodialysis, Hepatitis B, Hepatitis C, Incidence, Libya, Nosocomial infection, Prevalenc