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Background Panzi General Reference Hospital (HGR Panzi) in the Democratic Republic of Congo follows a large number of patients living with HIV-1 (PLWHIV). Although antiretrovirals (ARVs) are available, HIV-1 viral load (HIV-VL) measurement has only been implemented in the hospital since 2018. No data on ARV resistance levels and ARV dosage in plasma have yet been published for this region. We determined the prevalence of virological failure due to ARV resistance amongst patients and assessed the degree of genotypic resistance of the viral strains. Methods We performed an HIV-VL test and determined dosage of ARVs on samples collected from 205 PLWHIV at HGR Panzi between 2017 and 2018, including 13 ARV-naive patients. Genotypic resistance testing was performed on all samples with detectable HIV-VLs, and interpreted with the Agence Nationale de Recherches sur le Sida (ANRS) 2018 algorithm. Results Baseline resistance to NNRTIs was found in 2 of the 13 treatment-naive individuals (15%). ARV dosage was non-optimal for 44/192 of treated patients (22.9%), with an HIV-VL ≥1000 IU/mL for 40/192 (20.8%) of them. In particular, treatment-experienced viruses presented resistance to at least one NRTI (52.5%), to at least one NNRTIs (70%) or to at least one PIs (15%). Finally, two samples contained viruses with resistance polymorphism in the integrase gene. Conclusions The high level of resistance to ARVs observed during this study, mainly due to treatment compliance default, fully justifies the implementation of means for closer patient monitoring. The provision of VL tests and therapeutic education management tools in a PLWHIV follow-up remains an absolute necessity to best adapt the current treatment lines in this region.

Coronavirus disease 2019 (COVID-19) vaccination is reportedly efficient in people with HIV (PWH) but vaccine trials included participants with normal CD4+ T-cell counts. We analyzed seroconversion rates and antibody titers following two-dose vaccination in PWH with impaired CD4+ T-cell counts.We collected retrospective postvaccination SARS-COV-2 serology results available in a university hospital for PWH vaccinated between March and September, 2021 who were tested for antispike antibodies from 8 to 150 days following dose 2. Antibody titers were compared in PWH with CD4+ T-cell count less than 200 cells/μl, 200 CD4+ T-cell counts 500 cells/μl and CD4+ T-cell count greater than 500 cells/μl at vaccination.One hundred and five PWH were included: n = 54 in the CD4+ T-cell count less than 500 cells/μl group (n = 18 with CD4+200 cells/μl, n = 36 with 200 CD4+ 500 cells/μl) and 51 in the CD4+ T-cell count greater than 500 cells/μl group. They received two doses of BNT162b2 (75%), mRNA-1273 (8.5%), or ChAdOx1 nCoV-19 (16.5%). The median time from vaccine dose 2 to serology was consistent across all groups (73 days, interquartile range [29-97], P = 0.14). Seroconversion rates were 100% in the CD4+ T-cell count greater than 500 cells/μl group but 89% in participants with CD4+ T-cell counts less than 500 cells/μl (22 and 5.5% seronegative in the CD4+ T-cell counts200 cells/μl and 200 CD4+ 500 cells/μl groups, respectively). Median antibody titers were 623.8 BAU/ml [262.2-2288] in the CD4+ greater than 500 cells/μl group versus 334.3 BAU/ml [69.9-933.9] in the CD4+ less than 500 cells/μl group (P = 0.003). They were lowest in the CD4+ less than 200 cells/μl group: 247.9 BAU/ml [5.88-434.9] (P = 0.0017) with only 44% achieving antibody titers above the putative protection threshold of 260 BAU/ml.PWH with CD4+ T-cell counts less than 500 cells/μl and notably less than 200 cells/μl had significantly lower seroconversion rates and antispike antibody titers compared with PWH with CD4+ T-cell counts greater than 500 cells/μl, warranting the consideration of targeted vaccine strategies in this fragile population.

Objectives Genotyping of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been instrumental in monitoring viral evolution and transmission during the pandemic. The quality of the sequence data obtained from these genotyping efforts depends on several factors, including the quantity/integrity of the input material, the technology, and laboratory-specific implementation. The current lack of guidelines for SARS-CoV-2 genotyping leads to inclusion of error-containing genome sequences in genomic epidemiology studies. We aimed to establish clear and broadly applicable recommendations for reliable virus genotyping. Methods We established and used a sequencing data analysis workflow that reliably identifies and removes technical artefacts; such artefacts can result in miscalls when using alternative pipelines to process clinical samples and synthetic viral genomes with an amplicon-based genotyping approach. We evaluated the impact of experimental factors, including viral load and sequencing depth, on correct sequence determination. Results We found that at least 1000 viral genomes are necessary to confidently detect variants in the SARS-CoV-2 genome at frequencies of ≥10%. The broad applicability of our recommendations was validated in over 200 clinical samples from six independent laboratories. The genotypes we determined for clinical isolates with sufficient quality cluster by sampling location and period. Our analysis also supports the rise in frequencies of 20A.EU1 and 20A.EU2, two recently reported European strains whose dissemination was facilitated by travel during the summer of 2020. Conclusions We present much-needed recommendations for the reliable determination of SARS-CoV-2 genome sequences and demonstrate their broad applicability in a large cohort of clinical samples.

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.

BackgroundSARS-CoV-2 genotyping has been instrumental to monitor virus evolution and transmission during the pandemic. The reliability of the information extracted from the genotyping efforts depends on a number of aspects, including the quality of the input material, applied technology and potential laboratory-specific biases. These variables must be monitored to ensure genotype reliability. The current lack of guidelines for SARS-CoV-2 genotyping leads to inclusion of error-containing genome sequences in studies of viral spread and evolution.ResultsWe used clinical samples and synthetic viral genomes to evaluate the impact of experimental factors, including viral load and sequencing depth, on correct sequence determination using an amplicon-based approach. We found that at least 1000 viral genomes are necessary to confidently detect variants in the genome at frequencies of 10% or higher. The broad applicability of our recommendations was validated in >200 clinical samples from six independent laboratories. The genotypes of clinical isolates with viral load above the recommended threshold cluster by sampling location and period. Our analysis also supports the rise in frequency of 20A.EU1 and 20A.EU2, two recently reported European strains whose dissemination was favoured by travelling during the summer 2020.ConclusionsWe present much-needed recommendations for reliable determination of SARS-CoV-2 genome sequence and demonstrate their broad applicability in a large cohort of clinical samples.

Background The ANRS-163 ETRAL trial, a switch study to an etravirine 200 mg/raltegravir 400 mg twice-daily regimen in 165 patients with HIV-1 infection, showed durable efficacy until Week 96. The aim of this work was to investigate in detail the virological rebounds (VRs), defined as at least one plasma HIV viral load (VL) >50 copies/mL. Methods Quantification of HIV-DNA level was assessed at baseline, Week 48 and Week 96 (n = 157). VLs were measured in seminal plasma at Week 48 (n = 26). Genotypic resistance testing by ultra-deep sequencing (UDS) for reverse transcriptase (RT) and integrase regions was performed at baseline and at the time of VR. Results In this study, 19 patients experienced VR, with 2 patients having virological failure (VF; two consecutive VLs >50 copies/mL). For the first patient with VF, UDS detected minority resistant variants only in RT (K103N, 9.6%; Y181C, 4.9%) at baseline. Some RT variants became dominant at VF (K101E, 86.3%; Y181C, 100.0%; G190A, 100.0%) and others emerged in integrase (Y143C, 2.4%; Q148R, 6.2%; N155H, 18.8%). For the second patient with VF, neither RT nor integrase mutations were detected at baseline and VF. Median HIV-DNA level was similar at baseline, Week 48 and Week 96 (2.17, 2.06 and 2.11 log10 copies/106 cells, respectively). Only one patient had a detectable seminal HIV VL (505 copies/mL). Conclusions The dual etravirine/raltegravir regimen as maintenance therapy was effective and the emergence of mutations in cases of VF was similar to that seen in other dual-regimen studies. No HIV-DNA level modification was evidenced by Week 96.

Background Ending the HIV pandemic must involve new tools to rapidly identify and control local outbreaks and prevent the emergence of recombinant strains with epidemiological advantages. Aim This observational study aimed to investigate in France a cluster of HIV-1 cases related to a new circulating recombinant form (CRF). The confirmation this CRF’s novelty as well as measures to control its spread are presented. Methods Phylogenetic analyses of HIV sequences routinely generated for drug resistance genotyping before 2018 in French laboratories were employed to detect the transmission chain. The CRF involved was characterised by almost full-length viral sequencing for six cases. Cases’ clinical data were reviewed. Where possible, epidemiological information was collected with a questionnaire. Results The transmission cluster comprised 49 cases, mostly diagnosed in 2016–2017 (n = 37). All were infected with a new CRF, CRF94_cpx. The molecular proximity of this CRF to X4 strains and the high median viraemia, exceeding 5.0 log10 copies/mL, at diagnosis, even in chronic infection, raise concerns of enhanced virulence. Overall, 41 cases were diagnosed in the Ile-de-France region and 45 were men who have sex with men. Among 24 cases with available information, 20 reported finding partners through a geosocial networking app. Prevention activities in the area and population affected were undertaken. Conclusion We advocate the systematic use of routinely generated HIV molecular data by a dedicated reactive network, to improve and accelerate targeted prevention interventions. Geosocial networking apps can play a role in the spread of outbreaks, but could also deliver local targeted preventive alerts.

Hepatitis D virus (HDV) is responsible for fulminant hepatitis and liver failure and accelerates evolution toward cirrhosis and hepatocellular carcinoma in hepatitis B virus (HBV)-infected patients. To date, treatment relies upon long-term administration of pegylated alpha-interferon with a sustained virological response in 30% of the patients. Very recently, new, promising anti-HDV therapies have been developed and are already being used in clinical trials. HDV RNA viral load (HDVL) monitoring must be an integral part of the management of the infected patients. However, HDV genus is characterized by a high genetic variability into eight genotypes (HDV-1 to -8), and most available in-house or commercial assays are useful for only a limited subset of genotypes. Results of a comparison of the performance of a new kit for HDVL quantification with the consensus in-house assay of the French National Reference Laboratory for HDV developed in 2005 are reported here. A total of 611 clinical samples of all HDV genotypes with various HDVL values, including several consecutive samples over several years from 36 patients, were studied. A specificity, sensitivity, and reproducibility evaluation was conducted using HDV-positive clinical samples, hepatitis A, B, C and E (HAV, HBV, HCV, and HEV, respectively) and HIV mono-infected samples, and the WHO HDV RNA international standard. Overall results were strictly comparable between the two assays (median difference, 0.07 log IU/ml), with high diagnosis precision and capacity. In summary, this new kit showed high performance in detection/quantification of HDVL, regardless of the genotype of the infecting strain used, and seems to be a suitable tool for patient management.

Highlights • SARS-CoV-2 was already spreading in France in late December 2019, 1 month before the first official cases in the country. • Early community spreading changes our knowledge of the COVID-19 epidemic. • This new case changes our understanding of the epidemic, and modelling studies should adjust to these new data., The COVID-19 epidemic is believed to have started in late January 2020 in France. Here we report a case of a patient hospitalised in December 2019 in an intensive care unit in a hospital in the north of Paris for haemoptysis with no aetiological diagnosis. RT-PCR was performed retrospectively on the stored respiratory sample and confirmed the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Based on this result, it appears that the COVID-19 epidemic started much earlier in France.

International audience; Background: HIV therapy reduces the CSF HIV RNA viral load (VL) and prevents disorders related to HIV encephalitis. However, these brain disorders may persist in some cases. A large population of antiretroviral-treated patients who had a VL > 1.7 log10 copies/mL in CSF with detectable or undetectable VL in plasma associated with cognitive impairment was studied, in order to characterize discriminatory factors of these two patient populations.Methods: Blood and CSF samples were collected at the time of neurological disorders for 227 patients in 22 centres in France and 1 centre in Switzerland. Genotypic HIV resistance tests were performed on CSF. The genotypic susceptibility score was calculated according to the last Agence Nationale de Recherche sur le Sida et les hépatites virales Action Coordonnée 11 (ANRS AC11) genotype interpretation algorithm.Results: Among the 227 studied patients with VL > 1.7 log10 copies/mL in CSF, 195 had VL detectable in plasma [median (IQR) HIV RNA was 3.7 (2.7–4.7) log10 copies/mL] and 32 had discordant VL in plasma (VL 1.7 log10 copies/mL. Resistance to antiretrovirals was observed in CSF for the two groups of patients.Conclusions: Fourteen percent of this population of patients with cognitive impairment and detectable VL in CSF had well controlled VL in plasma. Thus, it is important to explore CSF HIV (VL and genotype) even if the HIV VL is controlled in plasma because HIV resistance may be observed.

Hepatitis delta virus (HDV) is responsible for the most severe form of acute and chronic viral hepatitis. We previously proposed that the Deltavirus genus is composed of 8 major clades. However, few sequences were available to confirm this classification. Moreover, little is known about the structural and functional consequences of HDV variability. One practical consequence is the failure of most quantification assays to properly detect or quantify plasmatic HDV RNA. Between 2001 and 2014, 2,152 HDV strains were prospectively collected and genotyped in our reference laboratory by means of nucleotide sequencing and extensive phylogenetic analyses of a 400-nucleotide region of the genome (R0) from nucleotide 889 to 1289 encompassing the 3' end of the delta protein-coding gene. In addition, the full-length genome sequence was generated for 116 strains selected from the different clusters, allowing for in-depth characterization of the HDV genotypes and subgenotypes. This study clearly confirms that HDV genus is composed of eight genotypes (HDV-1 to -8) defined by an inter-genotype similarity >85% or >80%, according to the partial or full-length genome sequence, respectively. Furthermore, genotypes can be segregated into 2 to 4 subgenotypes, characterized by an inter-subgenotype similarity >90% (>84% for HDV-1) over the whole genome sequence. Systematic analysis of genome and protein sequences revealed highly conserved functional nucleotide and amino acid motifs and positions across all (sub)genotypes, indicating strong conservatory constraints on the structure and function of the genome and the protein. Conclusion: this study provides new insights into genetic diversity of HDV, provides a clear view of their geographical localization and allows speculating the hypothesis as to the worldwide spread of the virus, very likely from an initial African origin. This article is protected by copyright. All rights reserved.

Background Natural variation and mutations in the envelope protein (S) of hepatitis B virus can translate into HBsAg variants no longer detectable by conventional HBsAg assays. Objectives The aim of the study was to assess the performance of 13 commercial assays currently used for screening and clinical analysis of HBsAg variants. Study design The limit of detection (LOD) for each assay was established using two reference standards (WHO HBsAg 00/588 and the SFTS French reference). Sensitivity was evaluated using different panels. Panel 1 included 25 recombinant HBs variants at three concentrations, panels 2 and 4 included 8 recombinant HBsAg variants and 9 wild-type proteins (genotypes A–F), respectively, panel 3 included 16 natural HBsAg variants. Results LODs ranged from 0.011 to 0.095 IU/ml with the WHO standard, and from 0.021 to 0.326 ng/ml with the French reference. The overall percentage of positive signals using HBsAg variants ranged from 62.9% to 97.9%. Three substitutions: T123, D144A and G145, were negative at all concentrations with at least one assay. Discussion Our findings show that, although they fulfil CE requirements for analytical sensitivity (LODs below 0.13 IU/ml), HBsAg assays may vary in their capacity to detect HBsAg variants. This limit in diagnosis performance should encourage the health regulatory agencies to include HBsAg variant panels in the evaluation process.

Objectives: To estimate the prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-1-infected patients in France. Methods: Resistance mutations were sought in samples from 530 newly diagnosed HIV-1-infected patients from October 2006 to March 2007. Protease and reverse transcriptase mutations were identified from the 2007 Stanford Resistance Surveillance list. Results: Reverse transcriptase and protease resistance mutations were determined in 466 patients with duration of seropositivity

Study objective This study compares the effectiveness and cost-effectiveness of nurse-driven targeted HIV screening alongside physician-directed diagnostic testing (intervention strategy) with diagnostic testing alone (control strategy) in 8 emergency departments. Methods In this cluster-randomized, 2-period, crossover trial, 18- to 64-year-old patients presenting for reasons other than potential exposure to HIV were included. The strategy applied first was randomly assigned. During both periods, diagnostic testing was prescribed by physicians following usual care. During the intervention periods, patients were asked to complete a self-administered questionnaire. According to their answers, the triage nurse suggested performing a rapid test to patients belonging to a high-risk group. The primary outcome was the proportion of new diagnoses among included patients, which further refers to effectiveness. A secondary outcome was the intervention's incremental cost (health care system perspective) per additional diagnosis. Results During the intervention periods, 74,161 patients were included, 16,468 completed the questionnaire, 4,341 belonged to high-risk groups, and 2,818 were tested by nurses, yielding 13 new diagnoses. Combined with 9 diagnoses confirmed through 97 diagnostic tests, 22 new diagnoses were established. During the control periods, 74,166 patients were included, 92 were tested, and 6 received a new diagnosis. The proportion of new diagnoses among included patients was higher during the intervention than in the control periods (3.0 per 10,000 versus 0.8 per 10,000; difference 2.2 per 10,000, 95% CI 1.3 to 3.6; relative risk 3.7, 95% CI 1.4 to 9.8). The incremental cost was €1,324 per additional new diagnosis. Conclusion The combined strategy of targeted screening and diagnostic testing was effective.

To identify factors associated with virological response (VR) to an etravirine (ETR)-based regimen, 243 patients previously treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) were studied. The impact of baseline HIV-1 RNA, CD4 cell count, past NNRTIs used, 57 NNRTI resistance mutations, genotypic sensitivity score (GSS) for nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), and the number of new drugs used with ETR for the first time on the VR to an ETR regimen were investigated. Among the 243 patients, the median baseline HIV-1 RNA level was 4.4 log10copies/ml (interquartile range [IQR], 3.7 to 4.9) and the median CD4 count was 175 cells/mm3(IQR, 69 to 312). Patients had been previously exposed to a median of 6 NRTIs, 1, NNRTI, and 5 PIs. Overall, 82% of patients achieved a VR at month 2, as defined by a decrease of at least 1.5 log10copies/ml and/or HIV-1 RNA level of

Integrase (IN), the HIV-1 enzyme responsible for the integration of the viral genome into the chromosomes of infected cells, is the target of the recently approved antiviral raltegravir (RAL). Despite this drug's activity against viruses resistant to other antiretrovirals, failures of raltegravir therapy were observed, in association with the emergence of resistance due to mutations in the integrase coding region. Two pathways involving primary mutations on residues N155 and Q148 have been characterized. It was suggested that mutations at residue Y143 might constitute a third primary pathway for resistance. The aims of this study were to investigate the susceptibility of HIV-1 Y143R/C mutants to raltegravir and to determine the effects of these mutations on the IN-mediated reactions. Our observations demonstrate that Y143R/C mutants are strongly impaired for both of these activities in vitro . However, Y143R/C activity can be kinetically restored, thereby reproducing the effect of the secondary G140S mutation that rescues the defect associated with the Q148R/H mutants. A molecular modeling study confirmed that Y143R/C mutations play a role similar to that determined for Q148R/H mutations. In the viral replicative context, this defect leads to a partial block of integration responsible for a weak replicative capacity. Nevertheless, the Y143 mutant presented a high level of resistance to raltegravir. Furthermore, the 50% effective concentration (EC 50 ) determined for Y143R/C mutants was significantly higher than that obtained with G140S/Q148R mutants. Altogether our results not only show that the mutation at position Y143 is one of the mechanisms conferring resistance to RAL but also explain the delayed emergence of this mutation.

To identify mutations associated with the virological response (VR) to a tipranavir-ritonavir (TPV/r)-based regimen, 143 patients previously treated with protease inhibitor (PI) were studied. VR was defined by a decrease of at least 1 log10in, or undetectable, human immunodeficiency virus (HIV) RNA at month 3. The effect of each mutation in the protease, considering all variants at a residue as a single variable, on the VR to TPV/r was investigated. Mutations at six residues were associated with a lower VR (E35D/G/K/N, M36I/L/V, Q58E, Q61D/E/G/H/N/R, H69I/K/N/Q/R/Y, and L89I/M/R/T/V), and one mutation was associated with a higher VR (F53L/W/Y). The genotypic score M36I/L/V − F53L/W/Y + Q58E + H69I/K/N/Q/R/Y + L89I/M/R/T/V was selected as providing a strong association with VR. For the seven patients with a genotypic score of −1 (viruses with only mutation at codon 53), the percentage of responders was 100% and the percentages were 79%, 56%, 33%, 21%, and 0% for those with scores of 0, 1, 2, 3, and 4, respectively. The percentage of patients showing a response to TPV/r was lower for patients infected with non-clade B viruses (n= 16, all non-B subtypes considered together) than for those infected with clade B viruses (n= 127) (25% and 59%, respectively;P= 0.015). Most mutations associated with VR to TPV/r had not previously been associated with PI resistance. This is consistent with phenotypic analysis showing that TPV has a unique resistance profile. Mutations at five positions (35, 36, 61, 69, and 89) were observed significantly more frequently in patients infected with a non-B subtype than in those infected with the B subtype, probably explaining the lower VR observed in these patients.

Hepatitis delta virus (HDV), in association with hepatitis B virus, is responsible for severe acute and chronic hepatitis. Treatment of the infection relies on the long-term administration of high doses of alpha interferon (IFN), and the treatment efficiency is monitored by the detection of anti-HDV immunoglobulin M and HDV genome in serum. Like the case for other chronic viral infections, HDV genome quantification in serum should be useful for the follow-up of infected patients. The aims of this study were to develop a quantitative assay for the detection of any type of HDV in serum and to evaluate the benefit of HDV RNA quantification for the follow-up of chronically infected patients receiving IFN. A real-time reverse transcription-PCR assay was developed to quantify the HDV RNA load in serum. Its efficacy was evaluated with 160 serum samples, 76 of which were collected from 11 chronically infected patients who were treated with pegylated IFN. The assay was sensitive (100 copies/ml of serum) and efficient for all HDV types, including type 3 and the recently described types 5, 6, and 7. The viral load determinations for treated patients allowed us to identify different profiles of virological responses to IFN therapy with more accuracy than that attainable with the qualitative approach. In conclusion, we have developed a quantitative HDV RNA assay for serum which is adapted to the follow-up of antiviral treatment for patients infected with any HDV type. The assay will help us to understand the natural history of HDV infection and to define guidelines for the management of chronic delta hepatitis.

Objective: In October 2009 the French National Authority for Health recommended that HIV testing be proposed at least once to all persons aged 15 to 70 years in all healthcare settings. We examined whether routine HIV screening with a rapid test in emergency departments (EDs) was feasible without dedicated staff, and whether newly diagnosed persons could be linked to care. Methods: This one-year study started in December 2009 in 6 EDs in the Paris area, using the INSTI TM test. Eligible individuals were persons 18 to 70 years old who did not present for a vital emergency, for blood or sexual HIV exposure, or for HIV screening. Written informed consent was required. Results: Among 183 957 eligible persons, 11 401 were offered HIV testing (6.2%), of whom 7936 accepted (69.6%) and 7215 (90.9%) were tested (overall screening rate 3.9%); 1857 non eligible persons were also tested. Fifty-five new diagnoses of HIV infection were confirmed by Western blot (0.61% (95% CI 0.46–0.79). There was one false-positive rapid test result. Among the newly diagnosed persons, 48 (87%) were linked to care, of whom 36 were not lost to follow-up at month 6 (75%); median CD4 cell count was 241/mm 3 (IQR: 52–423/mm 3 ). Conclusions: Screening rates were similar to those reported in opt-in studies with no dedicated staff. The rate of new diagnoses was similar to that observed in free anonymous test centres in the Paris area, and well above the prevalence (0.1%) at which testing has been shown to be cost-effective.

Human immunodeficiency virus infection has a major impact on the natural history of chronic hepatitis B and favours the emergence of viral mutants. We describe an acute hepatitis D virus superinfection in an HIV-1-infected patient under HAART treatment who was previously a chronic carrier of a surface negative HBV variant resistant to lamivudine.

The aim of this study was to examine the genetic variability of the hepatitis B virus (HBV) and its significance. HBV genotypes, core promoter and precore mutants were characterized in 109 consecutive patients with biopsy-proven HBV chronic hepatitis. Genotypes A (26.6%), B (12.8%), C (18.3%), D (18.3%), and E (14.7%) indicate a wide genotypic distribution. Patients were from Asia (30.3%), Europe (28.4%), Sub Saharan Africa (23.9%), the Caribbean (10.1%), North Africa (5.5%), and Madagascar (1.8%). HBV genotypes A and D (HBV/A and /D) infected all subgroups except Asian patients. HBV/B or /C were found in 97% of Asian patients, whereas HBV/E only infected sub-Saharan African and Caribbean patients. Differences according to genotypes were: an increased prevalence of anti-HBe antibodies in patients infected with HBV/D (P = 0.003), higher serum transaminases in patients infected with HBV/A and/D (P = 0.043), more severe liver fibrosis in patients infected with HBV/A, /C and/D (P = 0.02). Precore and core promoter mutants were found in 87% of anti-HBe positive patients, and were associated with HBV/D (P = 0.04) and severe liver fibrosis (P = 0.002). It is concluded that HBV genotypes A, B, C, D, and E circulate in the Seine Saint Denis District, reflecting the geographical origin of patients. HBV/A, /C and/D seem to be associated with more severe hepatic disease.