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While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Africa, the prevalence of HBV/HIV coinfection and their associated risk factors in children remains unclear. In this review, we sought to assess HBsAg seroprevalence among 0- to 16-year-olds with and without HIV in West African countries and the risk factors associated with HBV infection in this population. Research articles between 2000 and 2021 that reported the prevalence of HBV and associated risk factors in children in West Africa were retrieved from the literature using the Africa Journals Online (AJOL), PubMed, Google Scholar, and Web of Science databases as search tools. StatsDirect, a statistical software, was used to perform a meta-analysis of the retained studies. HBV prevalence and heterogeneity were then assessed with a 95% confidence interval (CI). Publication bias was evaluated using funnel plot asymmetry and Egger’s test. Twenty-seven articles conducted across seven West African countries were included in this review. HBV prevalence among persons aged 0 to 16 years was 5%, based on the random analysis, given the great heterogeneity of the studies. By country, the highest prevalence was observed in Benin (10%), followed by Nigeria (7%), and Ivory Coast (5%), with Togo (1%) having the lowest. HBV prevalence in an HIV-infected population of children was (9%). Vaccinated children had lower HBV prevalence (2%) than unvaccinated children (6%). HBV prevalence with a defined risk factor such as HIV co-infection, maternal HBsAg positivity, undergoing surgery, scarification, or being unvaccinated ranged from 3–9%. The study highlights the need to reinforce vaccination of newborns, screening for HBV, and HBV prophylaxis among pregnant women in Africa, particularly in West Africa, to achieve the WHO goal of HBV elimination, particularly in children.

Epstein–Barr virus DNA viral load is used as a surrogate marker to start Rituximab in transplant recipients at risk of developing PTLD. However, an elevated EBV DNAemia does not discriminate lymphoproliferation and replication. We designed a new molecular assay (methyl-qPCR) to distinguish methylated versus unmethylated viral genomes. In blood, viral genomes were highly methylated in EBV primary infections, PTLD and 4/5 transplant recipients with high viral load. The only patient with under-methylated EBV genomes did not respond to rituximab. Methyl-qPCR is a convenient method to discriminate between latent and lytic EBV genomes and could be useful in treatment decisions.

International audience; RT-PCR is the reference method for diagnosis of a Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection. During the setting up of 6 SARS-CoV-2 RT-PCR assays in our laboratory, comparative evaluations were systematically undertaken and allowed to evidence major discrepancies on cycle threshold RT-PCR results between techniques. These tendencies were confirmed in routine application when analyzing sequential samples from the same patients. Our aim was to examine the impact of the technique among factors influencing RT-PCR result, a far surrogate of 'viral load' in the heterogeneous environment of respiratory specimens.

We report evaluation of 30 assays’ (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-021-04232-3.

The control of STIs among adolescents is a recognised health priority in France.1 There are limited data on STI epidemiology among adolescents both across Europe and at the global level.2–4 We report a cross-sectional study to describe the cascade of care (number tested, diagnosed, treated) for youngsters (≤18 years) attending Free HIV and STI Information, Screening and Diagnosis Clinics (CeGIDD) in Paris for consultation on STIs. HIV, serology or rapid test, anti-HCV, HBsAg, anti-HBcorAb, Chlamydia, Gonococci and Mycoplasma specimens for PCR were collected as part of the routine approach at STI diagnosis. Syphilis serology was performed only in patients with more than 10 partners each year, migrants and men who have sex with men. CeGIDD was totally free of charge. The interval between first attendance and availability of test results was up to 7 days. Patients …

Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major pandemic ([1][1]). Diagnosis is based on detection of viral RNA, whereas the immune response to SARS-CoV-2 is measured by serological tests which detect antibodies (Abs) directed

BACKGROUND Previous large-scale studies have examined the effect of chronic hepatitis B virus (HBV) infection on overall and cause-specific mortality in individuals with HIV. However, few studies have collected data on the subclinical indicators of HBV that lead to these severe outcomes in the coinfected population. OBJECTIVE In this study, we aim to describe the procedures of a cohort study extension aimed at assessing HBV-DNA replication, serological markers of HBV (hepatitis B e antigen [HBeAg] and hepatitis B surface antigen), and liver fibrosis and how these subclinical outcomes relate to mortality in predominately tenofovir-treated, coinfected patients with HIV-HBV. We assessed the characteristics at cohort inclusion of those who participated in the cohort extension, as well as those who did not participate due to being lost to follow-up or death. METHODS Patients with HIV and chronic HBV who completed follow-up in a prospective cohort study conducted in 4 outpatient centers (Paris and Lyon, France; 2002-2011) were invited to participate in a cross-sectional visit from November 2016 to March 2018, during which a comprehensive evaluation of HIV- and HBV-related disease was undertaken. Virological and clinical data since the previous study visit were retrospectively collected. RESULTS Of the 308 individuals enrolled in the cohort, 147 (47.7%) participated in the cross-sectional study. At this visit, most participants were HBeAg negative (111/134, 82.8% with available data), had undetectable HBV DNA (124/132, 93.9% with available data), and were undergoing antiretroviral therapy containing tenofovir disoproxil fumarate or tenofovir alafenamide (114/147, 77.6%). There were no significant differences in characteristics at cohort inclusion between those who did and did not complete the cross-sectional visit, except for a lower proportion with an AIDS-defining illness (30/147, 20.5% vs 49/161, 30.4%, respectively; P=.04). Of the 161 nonparticipating individuals, 42 (26.1%) died, 41 (25.4%) were lost to follow-up and known to be alive, and 78 (48.4%) were lost to follow-up with unknown vital status. Most differences in characteristics at cohort inclusion were observed between deceased individuals and those participating in the cross-sectional visit or those lost to follow-up. With this extension, the median follow-up time of the overall cohort is presently 9.2 years (IQR 3.4-14.6). CONCLUSIONS Extended follow-up of the French HIV-HBV cohort will provide important long-term data on the subclinical trajectory of HBV disease in the coinfected population. The biases due to the relatively high rate of those lost to follow-up need to be assessed in future studies of this cohort. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/24731

Background: The virus responsible of severe acute respiratory syndrome named SARS-CoV-2 and causing the new coronavirus disease (COVID-19) has gone global within three months. The current gold standard technique used to detect SARS-CoV-2 is real-time reverse transcription-polymerase chain reaction (rRT-PCR) from naso-pharyngeal swabs but it may be negative in up to 30% of COVID-19 patients. Detection of specific antibodies against SARS-CoV-2 may therefore enhance sensitivity of the current biological diagnosis, as well as monitor the extent of the epidemics in global or specific population, such as health-care worker. Many serological assays are currently available, but their clinical performances are still to be evaluated. Material and Method: A total of 2,594 serum samples collected from patients with SARS-CoV-2 infection documented by a positive rRT-PCR were enrolled in this study. They were tested for IgM/IgG/IgA against SARS-CoV-2 using 31 commercial assays. Antibody response was assessed depending on the onset of symptoms. In addition, 1,996 pre-epidemic serum samples expected to be negative were tested to assess specificity. Results: Rapid tests for qualitative detection of anti-SARS-CoV-2 antibodies (RDTs) achieved 77.4-100%, and ELISA/CLIA (ELISA) assays 58.8-100% for SARS-CoV-2-specific total antibodies (TAb) specificity. From 15 days after onset of symptoms, 13/18 RDT and 8/13 ELISA reached sensitivity > 90%. However, only 4 RDT and 3 ELISA assays fitted both sensitivity (> 90%) and specificity (> 98%) criteria according to French recommendations. Conclusions: Serology may offer valuable information during the course of COVID-19 pandemic, at the condition that commercial assays give reliable results. Contrasted performances were observed among the 31 commercial assays we evaluated, which underlines the importance of independent evaluation before clinical implementation. Funding Statement: This study was funded by the Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (ANRS, AC43)". Declaration of Interests: JM Pawlotsky has served as an advisor and/or a speaker for Abbvie, Gilead, GlaxoSmithKline, Merck, Regulus and Siemens Healthcare. C Vauloup-Fellous served as un expert (rubella and CMV serology) for Abbott Diagnostics, Roche Diagnostics, Siemens Healthcare and DiaSorin. No other authors have any competing interests to declare. Ethics Approval Statement: The study was carried out in accordance with the Declaration of Helsinki. This work was a retrospective non-interventional study with no addition to standard care procedures. Reclassification of biological remnants into research material after completion of the ordered virological tests was approved by the local interventional review board of hospital. According to the French Public Health Code (CSP Article L.1121-1.1) such protocols are exempted from individual informed consent.

This retrospective study evaluated the impact of a pre-emptive rituximab (RTX) strategy for Epstein-Barr virus (EBV) reactivation on immune recovery and outcomes of 219 high-risk recipients undergoing allogeneic stem cell transplantation (allo-SCT) for hematological malignancies or bone marrow failure. One-hundred and seven patients received pre-emptive RTX for EBV reactivation (RTX group) and 112 did not (control group). The median onset time of EBV reactivation was 49 days (range, 14-561), including five patients who developed post-transplant lymphoproliferative disorder (EBV-PTLD). RTX and control groups were pair-matched to assess the impact of RTX on all endpoints. In RTX patients, CD19 + B cells were significantly decreased until 1-year post-transplant, so were immunoglobulin levels. Twenty-one patients (17%) developed RTX-related neutropenia. There was, in the RTX group, a trend towards a lower cumulative incidence of chronic GvHD (P = 0.059). Overall survival, progression-free survival, non-relapse mortality, relapse incidence, and incidence of overall infections at 2 years following allo-SCT were comparable in the two groups. We conclude that pre-emptive RTX, despite inducing a delayed B-cell reconstitution and a high risk of RTX-related neutropenia, may be considered as a worthwhile treatment, given the absence of negative impact on post allo-SCT outcomes and a low incidence of EBV-PTLD.

We evaluated the safety and immunogenicity of the BNT162b2 vaccine in 52 patients with multiple myeloma (MM). Median age was 71.3 (range, 39.6-90.8) years. 26 (50%) patients had received active treatment including an immunomodulatory drug (IMiD) (n=21), an anti-CD38 monoclonal antibody (n=11) and/or a proteasome inhibitor (n=4). 21 had received previous treatment interrupted at a median of 27.5 (range, 3.5-169.3) months before first vaccine inoculum. 5 patients had indolent untreated MM. 35 patients had a history of autologous hematopoietic cell transplantation (HSCT) performed at a median of 44.4 (range, 3.5-169.3) months before first vaccine inoculum. The vaccination was well tolerated with few non-severe adverse events. Immune efficacy evaluated by antibody seroconversion showed a significant increase of anti-Spike (S) IgG antibodies between day (d)28 and d42 (p= 3100 UA/mL). We found that patients’ age (>=71 years versus 25 versus = 120/L) had no impact on achievement of a protective anti-S IgG level after two BNT162b2 inocula. In contrast, male gender, and ongoing chemotherapy were associated with a significantly decreased probability of achieving the defined protective anti-S IgG level after two BNT162b2 inocula [odds ratio (OR) 0.126, 95% confidence interval (95% CI) 0.022-0.709, p=0.02; OR 0.146, 95%CI 0.025-0.866, p=0.03, respectively]. Finally, using the IFN-g ELISPOT assay in 12 patients, we found a significant increase in T cell response in 12 MM patients against the S protein, with 7 patients (58%) having an anti-S IgG positive ELISPOT after the second BNT162b2 inoculum. Conclusion These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with MM, but only around half of the patients are likely to achieve effective immune protection against COVID-19.

Resume La majorite des sujets infectes par le virus de l’hepatite C developpe une infection chronique du foie pouvant aboutir, en l’absence de traitement, a des complications hepatiques severes, telles que la cirrhose ou le carcinome hepatocellulaire. Un traitement antiviral peut en revanche guerir cette infection chronique, reduisant ainsi la morbidite et mortalite hepatique qui lui sont associees. La prise en charge therapeutique de l’hepatite C connait depuis quelques annees des avancees decisives, grâce au developpement d’antiviraux directs dont la combinaison permet aujourd’hui de guerir une grande majorite des patients traites. Nous reviendrons dans cet article sur ces avancees therapeutiques ainsi que sur les combinaisons therapeutiques disponibles, avant de detailler les principaux enjeux du futur de cette prise en charge.

Background Previous large-scale studies have examined the effect of chronic hepatitis B virus (HBV) infection on overall and cause-specific mortality in individuals with HIV. However, few studies have collected data on the subclinical indicators of HBV that lead to these severe outcomes in the coinfected population. Objective In this study, we aim to describe the procedures of a cohort study extension aimed at assessing HBV-DNA replication, serological markers of HBV (hepatitis B e antigen [HBeAg] and hepatitis B surface antigen), and liver fibrosis and how these subclinical outcomes relate to mortality in predominately tenofovir-treated, coinfected patients with HIV-HBV. We assessed the characteristics at cohort inclusion of those who participated in the cohort extension, as well as those who did not participate due to being lost to follow-up or death. Methods Patients with HIV and chronic HBV who completed follow-up in a prospective cohort study conducted in 4 outpatient centers (Paris and Lyon, France; 2002-2011) were invited to participate in a cross-sectional visit from November 2016 to March 2018, during which a comprehensive evaluation of HIV- and HBV-related disease was undertaken. Virological and clinical data since the previous study visit were retrospectively collected. Results Of the 308 individuals enrolled in the cohort, 147 (47.7%) participated in the cross-sectional study. At this visit, most participants were HBeAg negative (111/134, 82.8% with available data), had undetectable HBV DNA (124/132, 93.9% with available data), and were undergoing antiretroviral therapy containing tenofovir disoproxil fumarate or tenofovir alafenamide (114/147, 77.6%). There were no significant differences in characteristics at cohort inclusion between those who did and did not complete the cross-sectional visit, except for a lower proportion with an AIDS-defining illness (30/147, 20.5% vs 49/161, 30.4%, respectively; P=.04). Of the 161 nonparticipating individuals, 42 (26.1%) died, 41 (25.4%) were lost to follow-up and known to be alive, and 78 (48.4%) were lost to follow-up with unknown vital status. Most differences in characteristics at cohort inclusion were observed between deceased individuals and those participating in the cross-sectional visit or those lost to follow-up. With this extension, the median follow-up time of the overall cohort is presently 9.2 years (IQR 3.4-14.6). Conclusions Extended follow-up of the French HIV-HBV cohort will provide important long-term data on the subclinical trajectory of HBV disease in the coinfected population. The biases due to the relatively high rate of those lost to follow-up need to be assessed in future studies of this cohort. International Registered Report Identifier (IRRID) DERR1-10.2196/24731

BACKGROUND AND AIM The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis. METHODS Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region. RESULTS The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P

Introduction Le 10 mars 2020, l’OMS a déclaré pandémique la diffusion du SARS-CoV2 en recommandant de pratiquer de façon massive le dépistage du virus. Cette épidémie s’est installée alors que les épidémies hivernales de virus respiratoires n’étaient pas encore achevées. Afin de mieux comprendre les étiologies des syndromes grippaux en période COVID-19, nous avons analysé les prélèvements effectués dans un centre de dépistage hospitalier Francilien au tout début de l’épidémie. Matériels et méthodes La période d’étude s’est étendue du 28 février au 27 mars 2020. Tout patient consultant pour une recherche de SARS-CoV2 par RT-PCR dans le cadre d’un syndrome grippal a bénéficié d’une PCR multiplex pour les autres virus respiratoires. Les caractéristiques démographiques, cliniques et virologiques des consultants ont été analysées et les variables associées aux prélèvements positifs pour le SARS-CoV ou les autres virus ont été recherchées par régression logistique. Résultats Au total 707 patients ont consulté pendant la période d’étude et 468 patients ont bénéficié de la recherche de SARS-CoV2 et autres virus respiratoires. L’âge médian (IQR) était de 37 ans (29–50) avec 139 hommes (29,7 %). La prévalence du SARS-CoV2 était de 37,4 % (IQR : 33,01–41,8), et 37 sujets (7,9 %) étaient positifs pour d’autres pathogènes : Influenza A – 6 (1,3 %), Influenza B – 7 (1,5 %), Metapneumovirus – 5 (1,1 %), Rhinovirus – 4 (0,9 %), Coronavirus (229E, HKU1) – 3 (0,6 %), Adenovirus – 2 (0,4 %), Enterovirus – 4 (0,9 %), M. pneumoniae – 1 (0,2 %), Virus Respiratoire syncytial – 1 (0,2 %), infection mixte hors SARS-CoV-2 – 4 (0,9 %). À noter qu’aucun agent pathogène n’a été retrouvé chez 256 consultants. Les symptômes d’anosmie, fièvre et céphalées étaient plus fréquemment présents chez les sujets avec SARS-CoV2 comparés aux autres pathogènes (respectivement 26,3 % vs 2,7 %, p

When assessing hepatitis B virus (HBV) status in clinical settings, it is unclear whether self-reports on vaccination history and previous HBV-test results have any diagnostic capacity. Of 3997 participants in a multi-centre HBV-screening study in Paris, France, 1090 were asked questions on their last HBV-test result and vaccination history. Discordance between self-reported history compared with infection status (determined by serology) was calculated for participants claiming ‘negative’, ‘effective vaccine’, ‘past infection’, or ‘chronic infection’ HBV-status. Serological testing revealed that 320 (29.4%) were non-immunised, 576 (52.8%) were vaccinated, 173 (15.9%) had resolved the infection and 21 (1.9%) were hepatitis B surface antigen positive. In total 208/426 (48.8%) participants with a self-reported history of ‘negative’ infection had a discordant serological result, in whom 128 (61.5%) were vaccinated and 74 (35.6%) had resolved infections. A total of 153/599 (25.5%) participants self-reporting ‘effective vaccine’ had a discordant serological result, in whom 100 (65.4%) were non-immunised and 50 (32.7%) were resolved infections. Discordance for declaring ‘past’ or ‘chronic infection’ occurred in 9/55 (16.4%) and 3/10 (30.0%) individuals, respectively. In conclusion, self-reported HBV-status based on participant history is partially inadequate for determining serological HBV-status, especially between negative/vaccinated individuals. More adapted patient education about HBV-status might be helpful for certain key populations.

Background Occult hepatitis B infection (OBI) is recognized as a risk factor for cirrhosis and hepato-cellular carcinoma. However, OBI brings together a large spectrum of patients who might harbor different characteristics and prognosis. Methods We analyzed the databases of a university hospital in Paris to identify OBI among patients (n = 3966) concomitantly tested for hepatitis B virus (HBV) DNA and serology during a 7-year period. OBI patients were gathered into clinical entities according to their clinical records. Results Forty-seven OBIs were identified (1.2%). All patients had detectable anti-HBc, isolated (n = 26) or associated with anti-HBs (n = 21). The proportion of OBIs was 3.4% for patients with isolated anti-HBc and 4.2% for patients with both anti-HBc and anti-HBs. Four clinical categories of OBI patients were identified: patients with a passed HBV infection with HBs Ag clearance (group A, 23.4%); HBV-exposed patients receiving immunosuppressive therapy (group B, 29.8%); HIV/HBV-coinfected patients with therapy discontinuation (group C, 17%); HBV-exposed patients with severe liver conditions (group D, 29.8%). Significant follow-up was available for 32 patients, showing a more deleterious prognosis in group D patients, associated more with their underlying condition than the OBI status. Conclusions OBI is a heterogeneous condition with various clinical implications.

OBJECTIVE This study determines rates and risk factors associated with hepatitis B surface antigen (HBsAg) and hepatitis B 'e' antigen (HBeAg) seroclearance, two important prognostic indicators during infection with hepatitis B virus (HBV), in a large contemporary cohort of patients coinfected with HIV-HBV. DESIGN Prospective cohort study of predominately antiretroviral therapy (ART) experienced, coinfected patients. METHODS Participants enrolled in the French HIV-HBV Cohort had complete HBV serological battery conducted at inclusion and every yearly visit. Piecewise-exponential survival models were used to determine risk factors associated with seroclearance. RESULTS A total of 290 patients, of whom 151 (52.1%) were HBeAg positive, had been followed for a median 7.4 years (interquartile range [IQR] = 3.1-8.0). Tenofovir (TDF) containing ART became increasingly more frequent, as rates of undetectable HBV-DNA increased accordingly (at baseline = 39.3%, end of follow-up = 91.0%). In HBeAg-positive patients, 60 of 151 had HBeAg seroclearance (cumulative 46.4% at end of follow-up) after a median 3.0 years (IQR = 2.0-4.9). Overall, 17 of 290 patients had HBsAg seroclearance (cumulative 7.4% at end of follow-up) after a median 4.6 years (IQR = 2.1-7.2). Lower levels of time-averaged cumulative HBV-DNA were significantly associated with both HBeAg and HBsAg seroclearance (P

The aim of this pilot study was to analyze the Hepatitis C Virus (HCV) genotypes circulating in Senegal among Drug User (DUs), using Dried Blood Spots (DBS) as RNA source for molecular assays. Heroin and/or cocaine users (n = 506) were recruited in Dakar from April to July 2011, using a Respondent Driven Sampling (RDS) method. DBS preparation consisted of five drops of whole blood from finger applied to a Whatman paper card. HCV infection was screened by the detection of anti-HCV antibodies, using a rapid immune-chromatographic test. HCV RNA was quantified on anti-HCV positive DBS, using the Abbott RealTime HCV® Genotyping was performed on DBS with detectable viral load with Versant® HCV Genotype 2.0 Assay (LiPA) and Abbott RealTime HCV Genotype II assay®. Among the 506 participants, 120 were tested as positive for anti-HCV antibodies and their samples were analyzed for HCV RNA viral load and genotype. Out of the 120 DBS tested, HCV RNA was detected on 25 (20.8%). The median viral load was 15,058 IU/ml (ranging from 710 to 766,740 IU/ml). All positive DBS were suitable for the genotyping assay, that showed a predominance of genotype 1 (21/25) including 16 genotypes 1a and 5 genotypes 1b. HCV genotype 1 prevails in a DU population in Dakar. DBS could be useful for HCV RNA genotyping, but optimal storage conditions should required avoiding RNA impairment. Acknowledging this limitation, DBS could be a great interest for detecting and genotyping HCV viremic patients. J. Med. Virol. 89:484-488, 2017. © 2015 Wiley Periodicals, Inc.

Background Hepatitis B surface antigen (HBsAg)-seroconversion, or loss of HBsAg and acquisition of anti-hepatitis B surface (HBs) antibodies, defines functional cure of chronic hepatitis B virus (HBV) infection. After HBsAg-loss, little is known regarding the development of anti-HBs antibodies and even less so in individuals co-infected with HIV. Objectives To determine anti-HBs antibody kinetics after HBsAg-loss and explore determinants of HBsAg-seroconversion in HIV-HBV co-infected patients. Study design Patients enrolled in the French HIV-HBV cohort were included if they had >1 study visit after HBsAg-loss. Individual patient kinetics of anti-HBs antibody levels were modeled over time using mixed-effect non-linear regression, whereby maximum specific growth rate and maximal level of antibody production were estimated from a Gompertz growth equation. Results Fourteen (4.6%) of 308 co-infected patients followed in the cohort exhibited HBsAg-loss, all of whom were undergoing antiretroviral therapy. Nine (64.3%) of these patients achieved HBsAg-seroconversion during a median 3.0 years (IQR = 1.1–5.1) after HBsAg-loss. Across individuals with HBsAg-seroconversion, the fastest rates of antibody growth ranged between 0.57–1.93 year−1 (population maximum growth rate = 1.02) and antibody production plateaued between 2.09–3.66 log10 mIU/mL at the end of follow-up (population maximal antibody levels = 2.66). Patients with HBsAg-seroconversion had substantial decreases in HBV DNA viral loads (P = 0.03) and proportion with elevated ALT levels (P = 0.02) and HBeAg-positive serology (P = 0.08). No such differences were observed in those without HBsAg-seroconversion. Conclusions Most co-infected patients with HBsAg-seroconversion produced and maintained stable antibody levels, yet kinetics of anti-HBs production were much slower compared to those observed post-vaccination or after clearance of acute HBV-infection.

AIM: To determine whether hepatitis B virus (HBV)-testing could serve as a gateway to vaccinate non-immunized individuals in a low-prevalent country. METHODS: Non-immunized subjects participating in a multi-center, HBV-testing campaign in Paris, France were identified and contacted via telephone 3-9 mo after testing in order to determine vaccination status. Vaccination coverage was evaluated in per-protocol (for all respondents) and intent-to-treat analysis (assuming all non-responders did not vaccinate). RESULTS: In total, 1215/4924 (24.7%) enrolled subjects with complete HBV serology were identified as nonimmunized and eligible for analysis. There were 99/902 successfully contacted subjects who had initiated HBV vaccination after screening: per-protocol, 11.0% (95%CI: 9.0-13.2); intent-to-treat, 8.2% (95%CI: 6.7-9.8). In multivariable analysis, vaccination was more likely to be initiated in individuals originating from moderate or high HBV-endemic countries (P < 0.001), patients with limited healthcare coverage (P = 0.01) and men who have sex with men (P = 0.02). When asked about the reasons for not initiating HBV vaccination, the most frequent response was "will be vaccinated later" (33.4%), followed by "did not want to vaccinate" (29.8%), and "vaccination was not proposed by the physician" (21.5%). Sub-group analysis indicated a stark contrast in vaccination coverage across centers, ranging from 0%-56%. CONCLUSION: HBV-vaccination after HBV screening was very low in this study, which appeared largely attributed to physician-patient motivation towards vaccination. Increased vaccination coverage might be achieved by emphasizing its need at the organizational level.

Tenofovir (TDF) is considered the ideal treatment for patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV). However, certain coinfected patients exhibit incomplete viral suppression, with persistent, and sometimes transient, bouts of HBV replication. The reasons for this, including clinical effect, are unclear. A total of 111 HIV-HBV-infected patients undergoing TDF-containing antiretroviral therapy were prospectively followed. Serum HBV-DNA viral load, hepatitis surface (HBsAg) and e antigen (HBeAg) status were obtained at baseline and every 6-12 months. Amino acid (aa) changes on the polymerase gene were assessed using direct sequencing after nested polymerase chain reaction in patients with persistent viremia (PV). After a median of 74.7 months (interquartile range: 33.4-94.7), virological response (VR; 2,000 IU/mL) was rare (4 of 111; 3.6%) and was associated with nonadherence. At TDF initiation, patients with stabilized VR had significantly higher nadir CD4+ count, compared to those with transient PV (P = 0.006) or LL-PV (P = 0.04). No consistent aa changes, other than those associated with lamivudine resistance, were observed in patients with persistent viremia. Importantly, HBeAg loss, HBeAg seroconversion, and HBsAg loss only occurred in patients with stabilized VR. Two patients with stabilized VR developed hepatocellular carcinoma and 2 with LL PV died, 1 of a liver-related cause. Conclusion: Suboptimal HBV control during TDF treatment has a negative effect on serological outcomes, but not necessarily clinical events. Immunoregulation may provide more insight into this phenomenon. (Hepatology 2014;60:497–507)

Background & Aims In patients infected with hepatitis B virus (HBV) and HIV, hepatitis B ‘e’ antigen (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) may be used to predict short-term HBeAg and HBsAg loss, respectively. To determine if these quantifiable markers also provide accurate prediction of antigen loss during long-term, extensive tenofovir (TDF) treatment and to further establish qHBsAg profiles associated with HBsAg seroconversion. Methods Prospective study of 111 co-infected, antiretroviral-experienced patients undergoing a TDF-containing regimen for >12 months. HBV-DNA viral load, qHBeAg [Paul Ehrlich Institute Units (PEIU)/ml] and qHBsAg were quantified at baseline and every 6–12 months. Sensitivity (Se) and specificity (Sp) of qHBeAg criteria were calculated using a time-dependent receiver operator characteristic curve, and qHBsAg profiles were developed using a group-based trajectory model. Results After a median 74.2 months (IQR: 33.1–94.7) of TDF treatment, four patients had HBsAg seroconversion. Among the 78 (70.3%) HBeAg-positive patients, cumulative proportion with HBeAg loss was 42.0% (n = 23) at month 96. Baseline qHBeAg ≤100 PEIU/ml was the only significant factor for HBeAg loss (adjusted-HR = 2.36, 95% CI: 1.02–5.46) in multivariable analysis. In terms of predicting HBeAg-loss until month 96, qHBeAg ≤10 PEIU/ml was more accurate when evaluated at month 24 (Se = 0.73, Sp = 0.80) than month 12 (Se = 0.48, Sp = 0.90). All four patients with HBsAg seroconversion had profiles with large decreases in qHBsAg (>2 log10 IU/ml), not necessarily occurring during the first 12 months, which was infrequent in patients without seroconversion (8.4%, P

Introduction En France, la prevalence de l’hepatite B chronique (HBC) est estimee a 0,65 % en population generale, soit 1 280 000 porteurs chroniques de l’AgHBs, dont 150 000 ignorent leur statut serologique. Le depistage, obligatoire en cas de grossesse ou de don de sang est egalement recommande de facon plus large pour les personnes de plus de 16 ans non vaccinees susceptibles d’etre exposees au virus de l’hepatite B. Les Centres gratuits d’information, de depistage et de diagnostic (CeGIDD) integrent le depistage et la prevention de l’HBC ainsi que l’orientation vers le soin des personnes positives. L’objectif de cette etude est de decrire la cascade de soins suite a un depistage positif de l’AgHBs dans un CeGIDD, afin d’identifier les etapes sur lesquelles agir pour ameliorer l’efficience de la prise en charge. Materiels et methodes Il s’agit d’une etude transversale menee entre 2016 et 2018 chez tous les patients consultant dans un CeGIDD et ayant beneficie d’un depistage de l’AgHBs. Les etapes de la cascade de soins ont ete decrites a partir du depistage jusqu’a la mise sous traitement des sujets ayant une indication a etre traites. Resultats Parmi les 5741 personnes depistees, la prevalence de l’AgHBs positif etait de 1,1 % (n = 63, IC95 % : 0,86–1,40), avec un sex-ratio de4, 25 et un âge moyen de 31 ans ± 11 ans. La majorite des sujets etait originaire d’Afrique Subsaharienne (n = 59, 93,7 %) et 30 d’entre eux (47,6 %) n’avaient aucune couverture sociale. Une co-infection VIH etait associee dans 3 cas (3,8 %) et aucune co-infection VHC n’etait notee. Parmi ces sujets avec AgHBs positif, 81 % (n = 51)ont recupere leurs resultats,61,9 % (n = 39/63) ont realise leur bilan initial et 60,3 % (n = 38/63)ont beneficie d’un suivi ulterieur. Au total, 39,6 % patients (soit 25/63 des sujets depistes positifs) ont ete consideres comme perdus de vue a une des etapes de la cascade de soins. Selon les recommandations Europeennes de traitement de l’HBC, 10 patients parmi les 39 sujets evalues devaient beneficier d’un traitement (hepatite B chronique AgHBe positif = 1, hepatite B chronique AgHBe negatif = 5, immunotolerant de plus de 30 ans = 1 et co-infection VIH = 3). Le traitement a effectivement debute pour 8 des 10 sujets eligibles(Tenofovir n = 5, Entecavir n = 2 et Interferon n = 1). Conclusion Notre etude a retrouve une prevalence de l’HBC deux fois plus elevee que dans la population generale en France, et environ 40 % des sujets depistes positifs n’ont pas integre la cascade de soin (en particulier a ses stades precoces). Ces donnees suggerent qu’il est important d’augmenter l’adhesion au soin apres un depistage en CeGIDD afin d’optimiser les differentes etapes de la prise en charge de l’HBC en France.

International audience; Objectives: Worldwide, many infected individuals are unaware of their hepatitis B virus (HBV) status. We evaluated the effectiveness of HBV rapid testing in promoting linkage-to-care.Methods: In 2012, volunteers were recruited from five Parisian centers. Participants were randomized 1 : 1 to receive standard serology (S) or rapid testing (VIKIA-HBsAg/Quick Profile anti-HBsAb) with confirmatory serology (R+S). The primary endpoint was percentage of individuals with appropriate linkage-to-care (nonimmunized individuals starting vaccination or HBsAg-positive individuals receiving medical evaluation). The secondary outcomes were percentage receiving HBV-test results and performance of HBV rapid tests.Results: In total, 995 individuals were screened. Among the HBV-infection groups included in the primary endpoint (n=409), 20 (4.9%) received appropriate linkage-to-care, with no difference between S and R+S groups (5.7 vs. 4.1%, P=0.5). Two of eight HBsAg-positive participants had a medical visit (1/6 and 1/2 in the S and R+S groups, respectively) and 18/401 (4.5%) nonimmunized participants initiated HBV-vaccination (11/205 and 7/196). Factors that tended to be associated with linkage-to-care were female sex, birth country of high HBV prevalence, and extended medical stay. Test results were not obtained in 4.7% of participants, which was significantly higher in the S arm (P=0.02). Both sensitivity and specificity were 100% for the VIKIA-HBsAg rapid test and 94.4 and 80.8%, respectively, for the anti-HBsAb Quick Profile rapid test.Conclusion: Despite a higher proportion of participants obtaining their results in the R+S arm and better performance of anti-HBsAb rapid tests than described previously, we found no evidence that HBV screening based initially on rapid tests leads to increased HBV-vaccination rates or medical evaluation. This strategy should be evaluated in more hard-to-reach populations

Polymorphonuclear neutrophils (PMN) play a key role in host defenses against invading microorganisms but also potentiate inflammatory reactions in case of excessive or misdirected responses. Release of the alarmin high-mobility group box 1 (HMGB1) by cells that die at an inflammatory site may act as an alert signal for the immune system. We studied the effect of HMGB1 on human PMN migration, using whole-blood samples to avoid cell activation associated with isolation procedures. HMGB1 50–100 ng/ml reduced baseline PMN migration as well as formyl-methionyl-leucyl-phenylalanine- and IL-8-induced PMN chemotaxis. This inhibitory effect was mediated by the RAGE receptor. In contrast, a higher HMGB1 concentration (5,000 ng/ml) had a chemoattractant effect on PMN through IL-8 production. This effect required the engagement of Toll-like receptors 2 and 4 in addition to the RAGE receptor. The A box component of HMGB1, which antagonizes the endogenous protein, reduced chemotaxis and also strongly inhibited the enhancement of PMN migration observed with the highest HMGB1 concentration. In contrast, the B box, reported to be the active form of HMGB1, exerted a chemoattractant effect. These results strongly point to a key regulatory role of HMGB1 in PMN recruitment to inflammatory tissues. The A box component could potentially serve to inhibit inappropriate PMN recruitment during chronic inflammatory disorders associated with excessive HMGB1 release.

Highly active antiretroviral therapy is associated with carbohydrate metabolic alterations that may lead to diabetes. One consequence of hyperglycemia is the formation of advanced glycation end products (AGEs) that are involved in diabetes complications. We investigated the impact of AGEs on the infection of monocyte-derived dendritic cells (MDDCs) by HIV-1 and the ability of MDDCs to transmit the virus to T cells. We showed that AGEs could inhibit infection of MDDCs with primary R5-tropic HIV-1Ba-L by up to 85 ± 9.2% and with primary X4-tropic HIV-1VN44 by up to 60 ± 8.5%. This inhibitory effect of AGEs was not prevented by a neutralizing anti-receptor for advanced glycation end products (anti-RAGE) Ab, demonstrating a RAGE-independent mechanism. Moreover, AGEs inhibited by 70–80% the transmission in trans of the virus to CD4 T cells. Despite the inhibitory effect of AGEs on both MDDC infection and virus transmission in trans, no inhibition of virus attachment to cell membrane was observed, confirming that attachment and transmission of the virus involve independent mechanisms. The inhibitory effect of AGEs on infection was associated with a RAGE-independent downregulation of CD4 at the cell membrane and by a RAGE-dependent repression of the CXCR4 and CCR5 HIV-1 receptors. AGEs induce the secretion of proinflammatory cytokines IL-6, TNF-α, and IL-12, but not RANTES or MIP-1α, and did not lead to MDDC maturation as demonstrated by the lack of expression of the CD83 molecule. Taken together, our results suggest that AGEs can play an inhibiting role in HIV-1 infection in patients who accumulate circulating AGEs, including patients treated with protease inhibitors that developed diabetes.

Summary Virological interactions of hepatitis B (HBV), hepatitis C (HCV) and hepatitis D (HDV) viruses in HIV-infected patients have been poorly characterized especially under treatment influences. Undetection rates of hepatitis viruses were longitudinally analyzed in a 3-year cohort of 308 HIV–HBV co-infected patients and compared using Generalized Estimating Equation models adjusted for age, HIV-RNA, CD4 cell-count and antiviral treatment. Chronic hepatitis co-infection in HIV-infected patients (age years, SD) was: 265 HBV (40.7, 8.2); 19 HBV–HCV (39.7, 4.1); 12 HBV–HDV (35.2, 9.9); 12 HBV–HCV–HDV (39.2, 5.2). At inclusion, treatment with lamivudine/tenofovir was not significantly different between co-infection groups. HBV suppression was significantly associated with HDV (aOR = 3.85, 95%CI 1.13–13.10, P = 0.03) and HCV tri-infection (aOR = 2.65, 95%CI 1.03–6.81, P = 0.04), but marginally associated with HIV–HBV–HCV–HDV (aOR = 2.32, 95%CI 0.94–5.74, P = 0.07). In quad-infection, lower HDV-undetectability (vs HIV–HBV–HDV, P = 0.2) and higher HCV-undetectability (vs HIV–HBV–HCV, P = 0.1) were demonstrated. The degree of HBV suppression varied between visits and co-infection groups [range of aOR during follow-up (vs HIV–HBV co-infection): HIV–HBV–HCV = 2.23–5.67, HIV–HBV–HDV = 1.53–15.17]. In treated co-infected patients, HDV expressed continuous suppression over HCV- and HBV-replications. Peaks and rebounds from undetectable hepatitis B, C and/or D viremia warrant closer follow-up in this patient population. HDV-replication was uncontrolled even with antiviral treatment.

In this randomized-control trial, conducted at a free clinic in France for predominately immigrant populations without healthcare, we demonstrate that simultaneous HIV/HBV/HCV point-of-care rapid testing improves screening outcomes. Increased awareness of infection status likely helped link these patients to care., Background. In Europe and the United States, more than two thirds of individuals infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) and 15%–30% of human immunodeficiency virus (HIV)-positive individuals are unaware of their infection status. Simultaneous HIV-, HBV-, and HCV-rapid tests could help improve infection awareness and linkage-to-care in particularly vulnerable populations. Methods. The OptiScreen III study was a single-center, randomized, control trial conducted at a free clinic (“Médecins du Monde”, Paris, France). Participants were randomized 1:1 to receive 1 of 2 interventions testing for HIV, HBV, and HCV: standard serology-based testing (S-arm) or point-of-care rapid testing (RT-arm). The main study endpoints were the proportion of participants who became aware of their HIV, HBV, and HCV status and who were linked to care when testing positive. Results. A total of 324 individuals, representing mainly African immigrants, were included. In the S-arm, 115 of 162 (71.0%) participants performed a blood draw and 104 of 162 (64.2%) retrieved their test result. In comparison, 159 of 162 (98.2%) of participants randomized to the RT-arm obtained their results (P < .001). Of the 38 (11.7%) participants testing positive (HIV, n = 7; HBV, n = 23; HCV, n = 8), 15 of 18 (83.3%) in the S-arm and 18 of 20 (90.0%) in the RT-arm were linked-to-care (P = .7). In post hoc analysis assuming the same disease prevalence in those without obtaining test results, difference in linkage-to-care was more pronounced (S-arm = 60.0% vs RT-arm = 90.0%; P = .04). Conclusions. In a highly at-risk population for chronic viral infections, the simultaneous use of HIV, HBV, and HCV point-of-care tests clearly improves the “cascade of screening” and quite possibly linkage-to-care.

The long-term impact of tenofovir disoproxil fumarate (TDF) on hepatitis B virus (HBV) replication has not yet been studied in HIV-HBV-co-infected patients.We conducted a prospective study of HBV-DNA decay kinetics in 28 HIV-HBV-co-infected patients treated by TDF. HBV dynamics were studied using mixed linear models, and baseline factors affecting them were analysed using Cox models.The HBV-DNA load declined by a mean of 4.6 log copies/ml during follow-up (mean 71 weeks), and fell below the detection limit (200 copies/ml) in 21 patients. Inhibition of viral replication by TDF was associated with a decrease in alanine aminotransferase levels (125 versus 68 IU, P0.05). HBV-DNA decay was biphasic, with an rapid fall followed by a gradual decline. Baseline factors associated with a steeper first slope in the HBV-DNA decrease were high HBV load, positive hepatitis B e antigen (HBeAg) and YMDD mutations. Baseline factors increasing the time to reach an HBV-DNA level less than 200 copies/ml were high HBV load (150 days when HBV-DNA10 log, 316 days when HBV-DNA10 log) and positive HBeAg. Previous exposure to lamivudine or TDF-lamivudine did not modify HBV-DNA decrease under therapy in this population with a high prevalence of YMDD mutations.The long-term decline in HBV DNA under TDF is biphasic and is primarily influenced by the initial HBV load. However, the clinical significance of such an association remains moderate, and TDF can be efficiently included in the highly active antiretroviral therapy regimen of HIV-HBV-co-infected patients, regardless of HBV strains and their degree of replication.

Hypertrophic pseudo tumoral herpetic lesion is an uncommon presentation in immunocompromized hosts that can be refractory to established therapies. We describe bipolar anal and tonsilar herpetic tumoral lesions related to acyclovir-resistant HSV-2 in a human immunodeficiency virus-infected patient. Treatment with valacyclovir, cidofovir, and thalidomide failed and surgical excision was required.

To study the natural history and the current risk factors for cytomegalovirus (CMV) disease in the context of highly active antiretroviral therapy (HAART).Prospective multicentre cohort in 15 university hospitals in France.A group of 198 patients with CD4 cell count100 x 10(6) cells/l (or200 x 10(6) cells/l under HAART for at least 2 months), no previous CMV disease and CMV-positive serology were followed every 4 months clinically and for virological testing including HIV RNA and CMV blood markers (culture, pp65 antigenaemia, plasma CMV DNA and CMV late mRNA by the polymerase chain reaction).At inclusion, median CD4 was 77 x 10(6) cells/l (0-308) and 85% of the patients received protease inhibitors. The percentage of patients receiving HAART reached 99% at 12 months. After a follow-up of 23.6 months, the incidence of CMV disease was 3.2/100 patient-years [95% confidence interval (CI) 1.3-5.0]. In univariate Cox models, all the CMV markers, a CD4 cell count remaining75 x 10(6) cells/l and an HIV viral load100,000 copies/ml were predictive for CMV disease. The hazard ratios for CMV disease were 11 for blood culture; 14 and 70 for pp65 antigenaemia ofor = 1 andor = 100 nuclei/200,000 cells, respectively; 35 for plasma CMV DNA; 6 for CMV mRNA; 29 for CD475 x 10(6) cells/l; and 12 for HIV RNA100,000 copies/ml. In a stepwise multivariate analysis, only three covariates were independently associated with the occurrence of a disease: plasma CMV DNA, pp65 antigenaemiaor = 100 nuclei/200,000 cells and a CD4 count75 x 10(6) cells/l.CMV blood markers and CD4 count75 x 10(6) cells/l remain risk factors for CMV disease in patients receiving HAART. Analysis of plasma CMV DNA by the polymerase chain reaction is a reproducible and standardized tool that could be used as a decision marker for initiating CMV pre-emptive therapy.

Objective To evaluate the efficacy and safety of the foscarnet-ganciclovir combination in induction therapy (IT) and maintenance therapy (MT) for cytomegalovirus (CMV) central neurological disorders in HIV-infected patients. Design An open pilot non-comparative multicentre study. Methods Thirty-one patients with acute CMV encephalitis (CMVe) (n = 17) or CMV myelitis (CMVm) (n = 14) during the era before highly active antiretroviral therapy (HAART) received intravenous IT with foscarnet 90 mg/kg plus ganciclovir 5 mg/kg twice a day followed by MT. The primary endpoint was clinical efficacy, assessed at the end of the induction phase. Results The foscarnet-ganciclovir combination in IT resulted in a 74% (23 out of 31 patients) clinical improvement or stabilization. Eight patients did not respond clinically. Side-effects leading to drug discontinuation occurred in 10 patients during IT. Among the 23 patients who qualified for the maintenance phase, CMV disease progressed in 10, with a median time to the first relapse of 126 days (range 64-264 days). Overall, the median survival time was 3 months [95% confidence interval (CI), 2-4 months]. Conclusion The combination of foscarnet and ganciclovir can safely be used for CMV central nervous system (CNS) infection, with an improvement or stabilization in 74% of patients. Life-long MT with this combination is recommended as long as the immune system is profoundly impaired.

Multiple hepatitis co-infections are frequent in HIV-infected patients, often resulting in severe liver diseases that are difficult to treat. We report here the complete resolution of a chronic hepatitis B and D co-infection in a patient who was also infected with HCV and HIV. This cure was observed after 24weeks of combination therapy associating pegylated-IFN and ribavirin, which was initially given to treat HCV. An unexpected and extensive HDV replication was observed in this patient after HBs Ag had cleared from the serum, which was followed by a stable halt in HDV replication. Implications of this unusual observation will be discussed.

A molecular virology analysis performed in an HIV-hepatitis B virus (HBV) co-infected patient showed the emergence of an unusual HBV polymerase gene mutation (rt A181T) under adefovir therapy, conferring resistance to adefovir but not to tenofovir, as proved by in-vitro phenotypic analysis. This observation suggests that careful monitoring of co-infected patients is required to diagnose HBV resistance to nucleos(t)ide analogues, and that tenofovir may be active at least against some of the adefovir-resistant strains.

Objective To investigate the role of the Fas-Fas ligand (FasL) interaction in HIV-1-induced apoptosis of primary CD4+ T lymphocytes. Design Activated CD4+ T lymphocytes are the main target of HIV, and T-cell activation leads to the expression of Fas-FasL and enhances HIV-mediated apoptosis. Phytohemagglutinin-activated primary CD4+ T cells were infected with HIV; the process of cell death was examined, and whether the dying and dead cells were the productively infected cells. The modulation of Fas and FasL expression and its role in HIV-induced cell death was also investigated. Methods The number of viable and dead cells was determined by trypan blue exclusion. Apoptosis was quantified using an enzyme-linked immunosorbent assay measuring the release of cytoplasmic histone-associated DNA fragments. The percentage of HIV-infected cells was determined by FACS analysis, and viral production was assessed by a p24 core antigen assay. The following three markers, HIV-gp-120, annexin-V and 7-AAD, were used to monitor the apoptotic process in HIV-negative and positive cells. Fas and FasL expression was analyzed at the RNA level by reverse transcription polymerase chain reaction and at the protein level by flow cytometry. The contribution of Fas-FasL interactions to apoptosis was examined by blocking experiments using the antagonist ZB4 anti-Fas antibody. Results HIV-induced apoptosis in activated purified CD4+ T lymphocytes required infectious virus and was dose-dependent. Apoptosis in HIV-infected cultures was mostly confined to productively infected cells. The expression of Fas and FasL was not significantly modulated by infection and blocking Fas-FasL interactions did not reduce the extent of apoptosis. Conclusions HIV-induced apoptosis of activated CD4+ T cells in vitro is confined to productively infected cells and is not mediated by a Fas-FasL interaction.

Summary Background Consequences of latent cytomegalovirus (CMV) infection reactivation on inflammatory bowel disease (IBD) flare, as a flare-worsening factor or simple bystander, are debated. Impact of anti-viral treatment on IBD course is poorly known. Aim To assess the impact of CMV reactivation on patients hospitalised for IBD flare and the effect of anti-viral treatment on IBD flare in patients with CMV reactivation. Methods First, a population of UC patients from Saint-Antoine hospital, in flare with positive blood CMV PCR without anti-viral treatment (n = 26), were compared to matched patients with negative blood CMV PCR in a case–control study. Secondly, a total of 110 hospitalisations between October 2003 and May 2012 for IBD flare-up with CMV reactivation (80 diagnosed on blood PCR, 33 on tissue PCR) were identified in three French referral centres. Evolution following CMV reactivation diagnosis was compared between patients receiving anti-viral treatment and those who did not. Results In the case–control study, no differences were observed between the two groups regarding length of hospital stay and colectomy rate. Comparing treated and untreated patients, no differences were observed at inclusion regarding age, gender, IBD type, immunosuppressant, CRP and haemoglobin level. No differences were observed regarding CRP level decrease at 10 days and colectomy rate at 3 months. Anti-viral treatment was associated with lower serum albumin level at inclusion and longer hospitalisation. Conclusions CMV reactivation does not appear to alter the course of IBD flare. CMV treatment does not seem to impact the course of IBD. These results should be confirmed prospectively.

The efficacy and tolerance of telaprevir (TVR) was examined in 20 mostly cirrhotic HIV-hepatitis C genotype 1 (HCV-G1)-infected patients failing previous treatment with pegylated-interferon and ribavirin (PR). HCV-RNA less than 12 IU/ml was observed in 35.3% of patients at W2, 55.0% at W4, 65.0% at W12 and 55.0% at W24. All patients with virological failure (n = 9) exhibited V36M/R155K mutations. Early virological response was a determinant of HCV-RNA less than 12 IU/ml at W24 (P

Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents.

OBJECTIVE Hepatitis B surface (HBsAg) and envelope (HBeAg) antigen loss are the primary goals of treating chronic hepatitis B virus (HBV). Although their quantification is useful for other antivirals, such has not been the case with tenofovir disoproxil fumarate (TDF), particularly in HIV infection. DESIGN Prospective, multicenter, cohort study in 143 antiretroviral-experienced HIV-HBV-co-infected patients initiating TDF. METHODS HBsAg (IU/ml) and HBeAg levels (S/CO) were measured every 6 months. HBsAg and HBeAg decline (Δ) were assessed by mixed-effect linear models. Quantification criteria were used to assess predictability of antigen loss with time-dependent receiver operating characteristic curves. RESULTS After a median follow-up of 30.3 months, cumulative incidence rate of HBsAg loss was 4.0% (n = 4) in the entire study population and HBeAg loss was 21.0% (n = 17) in the 96 HBeAg-positive patients. ΔHBsAg was steady during follow-up (HBeAg-positive: -0.027; HBeAg-negative: -0.017 log(10) IU/ml per month), whereas ΔHBeAg ratio was strongly biphasic (-27.1 S/CO per month before and -6.5 S/CO per month after 18 months). Baseline HBeAg and ΔHBeAg were significantly different in patients harboring precore mutations (P < 0.01), whereas both ΔHBsAg and ΔHBeAg were significantly slower among HBeAg-positive patients with CD4(+) T-cell count less than 350 cells/μl (P < 0.05). HBeAg-ratio of 10 S/CO or less at 12 months of therapy was the optimal marker of HBeAg loss, with high sensitivity (0.82) and specificity (0.84) at 36 months. In patients with HBsAg loss, three of four (75.0%) patients had a baseline level of HBsAg of 400 IU/ml or less. CONCLUSION During TDF treatment, HIV-induced immunosuppression and HBV genetic variability are associated with differences in HBsAg and HBeAg decline among antiretroviral-experienced, co-infected patients. Considering the decline of HBsAg level is slow, further evaluation is needed to determine its role as a marker of therapeutic efficacy.

Background High mobility group box 1 protein (HMGB1) is a major endogenous danger signal that triggers inflammation and immunity during septic and aseptic stresses. HMGB1 recently emerged as a key soluble factor in the pathogenesis of various infectious diseases, but nothing is known of its behaviour during herpesvirus infection. We therefore investigated the dynamics and biological effects of HMGB1 during HSV-2 infection of epithelial HEC-1 cells. Methodology/Principal Findings Despite a transcriptional shutdown of HMGB1 gene expression during infection, the intracellular pool of HMGB1 protein remained unaffected, indicating its remarkable stability. However, the dynamics of HMGB1 was deeply modified in infected cells. Whereas viral multiplication was concomitant with apoptosis and HMGB1 retention on chromatin, a subsequent release of HMGB1 was observed in response to HSV-2 mediated necrosis. Importantly, extracellular HMGB1 was biologically active. Indeed, HMGB1-containing supernatants from HSV-2 infected cells induced the migration of fibroblasts from murine or human origin, and reactivated HIV-1 from latently infected T lymphocytes. These effects were specifically linked to HMGB1 since they were blocked by glycyrrhizin or by a neutralizing anti-HMGB1 antibody, and were mediated through TLR2 and the receptor for Advanced Glycation End-products (RAGE). Finally, we show that genital HSV-2 active infections also promote HMGB1 release in vivo, strengthening the clinical relevance of our experimental data. Conclusions These observations target HMGB1 as an important actor during HSV-2 genital infection, notably in the setting of HSV-HIV co-infection.

International audience; HIV-HBV-coinfected patients require optimal control of viral replication in order to prevent the development of severe comorbidities, such as liver cirrhosis and hepatocellular carcinoma. The genetic diversity of HBV is a poorly investigated factor of such viral replication in HIV-infected hosts. HBV genome diversity can be differentiated into two major aspects: genotypic and phenotypic. Genotypic diversity is more related to the natural history of HBV infection and genotypes are mostly determined by geographical origin of the hosts. Phenotypic diversity arises from attempts to escape from host immune surveillance (that is, precore, core and basal core promoter mutants), selection resulting from the use of treatments with weak genetic barrier (that is, pol mutants), exposure to hepatitis B immunoglobulin (that is, 'immune-escape' S gene mutants) or treatment-induced mutations from overlapping genes (that is, pol mutants inducing 'vaccine-escape' S gene mutants). pol mutations typically lead to uncontrolled viral replication, whereas S gene mutations can significantly alter hepatitis B surface antigen synthesis and reduce binding to antibodies, which renders individuals who are vaccinated or cured of HBV infection susceptible to infection. For patients coinfected with HIV, hepatitis B treatment options that aim to reduce the risk of HBV mutations from emerging must be seriously considered, not only from clinical but also public health perspectives.