Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe

Background: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. Methods: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. Results: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by ana

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

International audienceBackground: Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infectedindividuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwidecross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identifyparameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBVviremia.Methods: A multicenter collaborative cross-sectional study was launched in 19 French University hospitalsdistributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiologicalcharacteristics 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%) waslinked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic patternhighlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) underantiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypiclamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesionswere observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viralload 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-HBVdrugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimaladherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver diseaseprogression. These findings are strong arguments to further optimize clinical management and to promotevaccination in HIV-infected patients