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

Introduction: Hepatitis B is a major cause of death in patients with HIV who usually receive drugs active against hepatitis B virus (HBV). The variability of HBV DNA over time has been little studied. Recombination between different HBV genotypes has been described in many cross-sectional studies, but the frequency of intergenotypic and intragenotypic recombinations in individual patients is unknown., Methods: 32 HIV-positive and 11 HIV-negative patients who remained HBV viraemic despite antiviral therapy for at least 1 year were studied. Genotyping was based on line probe assays and genotype-specific PCR. The variability of HBV DNA over time was examined with restriction length and single-strand conformational polymorphism (RFLP-SSCP). HBV DNA sequences obtained by cloning a 2800 bp PCR fragment were analysed for phylogenetic parameters (diversity and selection pressure) and recombination was detected with RDP3 software., Results: Large fragments of HBV DNA could be amplified at two different time points in 33 patients. Marked quasi-species modifications occurred in 14 patients. In seven of these patients and in one patient with no change detectable by RFLP-SSCP, the 2800 bp fragment was cloned at two time points at least. In four (57%) of these seven patients, various intergenotypic or intragenotypic recombination events were detected between subvariants present in the initial quasi-species. Recombinant fragments mostly harboured antiviral resistance determinants and reflected a large increase in diversity and in positive selection pressure on the entire HBV quasi-species., Conclusions: In coinfected patients, HBV DNA recombination events are frequent during antiviral therapy, corresponding to increased positive selection pressure on the HBV quasi-species and to conservation of antiviral resistance mutations. In this population and at the individual level, recombination is a significant source of HBV genetic variability.

Aim: To evaluate the early virological response (EVR) to combined tenofovir-lamivudine or emtricitabine regimen in HBV/HIV-co-infected patients and the long-term efficacy of tenofovir., Methods: In this retrospective monocentric study, among the 166 HIV/HBV-co-infected patients regularly followed from 2003 to 2008 at Bichat Claude Bernard Hospital, 61 patients had received, either de novo combination therapy with tenofovir and lamivudine or emtricitabine (group I, n = 15) or add-on tenofovir to lamivudine therapy (group II, n = 46). The HBV polymerase region was sequenced and analysed for all patients with available samples., Results: All 15 group I patients achieved EVR vs 32 (82%) of group II patients (P = 0.15). Seven adherent group II patients met criteria for primary non-response, but achieved delayed response (DR) to therapy. In these seven patients, when compared with the 39 group II patients, there was a trend to longer duration of lamivudine pre-treatment and to higher rate of lamivudine-resistant mutants; and HBV genotype-G proportion was higher (P = 0.026). No virological breakthrough occurred after a median of 46 months follow up., Conclusion: In these HBV/HIV-co-infected patients, first-line HBV therapy with tenofovir and emtricitabine or lamivudine was associated with EVR. However, DR to tenofovir was observed in 15% of patients who added tenofovir to lamivudine therapy, of whom four of seven (57%) had genotype G-HBV infection. No resistance was evidenced after 46 months of therapy even in patients with DR to tenofovir. At last, a good renal safety profile of TDF was observed after a median follow-up of 4 years of therapy., (© 2011 John Wiley & Sons A/S.)

Background: Among 141 HIV-HBV-coinfected patients treated with tenofovir in our centre, 87% were good-responders to therapy. Seven patients showed a delayed response to tenofovir. The present study was performed to evaluate the quasispecies variability and the in vitro drug susceptibility to approved antiviral drugs of HBV genomes directly isolated from patients' sera., Methods: After purification of DNA from serum samples, full-length HBV DNA was amplified by PCR, cloned and sequenced. Drug sensitivity of HBV strains isolated from four delayed responders and five good-responders was assessed and compared to a wild-type HBV strain after transfection of the full genome into HepG2 cells., Results: Delayed responders, compared with good responders, showed a higher incidence of lamivudine-resistant mutations (71% and 35%, respectively; P=0.021) and a higher proportion of HBV genotype G (57% versus 16%, respectively; P=0.026). Clonal analysis demonstrated a higher variability of HBV quasispecies in delayed reponders than in good responders. In vitro analysis showed a lower efficacy of adefovir and tenofovir in delayed reponders. Furthermore, HBV genotype G strains showed a mild to weak susceptibility to tenofovir., Conclusions: The reason for the slow decline in HBV DNA level observed during therapy in delayed responders is not clear. Delayed responders showed higher quasispecies variability, a higher proportion of HBV genotype G and a mild in vitro decreased susceptibility to tenofovir and adefovir. A combination of these factors in heavily treatment-experienced HIV-infected patients could explain the lower tenofovir activity. These patients must be closely monitored to prevent prospective emergence of resistance to approved antiviral drugs.

The aims of this study were to assess the sociodemographic, epidemiological, clinical, and biological characteristics of French patients co-infected with human immunodeficiency virus-hepatitis C virus (HIV-HCV), as well as the management of their HCV infection. Data on 509 HIV-HCV co-infected patients, followed up at six French University Hospitals, were collected using a questionnaire. Student's t-test, Pearson's chi-square, Fisher's exact, and Fisher-Freeman-Halton's exact tests were used. The mean age of the patients was 38.3 years, and the male to female sex ratio 2.08; 88% of patients were born in Metropolitan France, and 20% were dependent on health benefits; 74% were intravenous drug users and 14% blood or blood product recipients. Forty-seven percent were in CDC classification stage A, 18% had a CD4+ count of <200, and 79% were undergoing current antiretroviral treatment. HCV RNA was positive in 84% (50% type 1, 13% untypable). Forty-four percent had normal alanine aminotransferase (ALT) levels, 24% alcohol consumption >15 g/day, and 51% had undergone liver biopsy (10% of which had cirrhosis). Histological grade was not related to ALT level or CD4+ count. Overall, 40% of patients had been treated for HCV infection. HCV treatment was significantly associated with performance of liver biopsy, histological grade, ALT level, CD4+ count, Centers for Disease Control (CDC) classification, but not with age or alcohol consumption. Rate of early response to treatment was fifty percent among patients treated with bitherapy. Eighty-nine percent of all patients with previous or current anti-HCV treatment had undergone liver biopsy. In conclusion, despite the difficulties in managing hepatitis C in HIV-infected patients, almost one-half of all patients in this study had received anti-HCV treatment., (Copyright 2003 Wiley-Liss, Inc.)

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