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Quasispecies Analysis and In VitroSusceptibility of HBV Strains Isolated from HIV–HBV-Coinfected Patients with Delayed Response to Tenofovir

Quasispecies Analysis and In VitroSusceptibility of HBV Strains Isolated from HIV–HBV-Coinfected Patients with Delayed Response to Tenofovir

Authors :
Lada, Olivier
Gervais, Anne
Branger, Michel
Peytavin, Gilles
Roquebert, Benedicte
Collin, Gilles
Fraqueiro, Gil
Moucari, Rami
Leclerc, Laurence
Martinot-Peignoux, Michelle
Matheron, Sophie
Marcellin, Patrick
Source :
Antiviral Therapy; January 2012, Vol. 17 Issue: 1 p61-70, 10p
Publication Year :
2012

Abstract

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 vitrodrug 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 vitroanalysis 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 vitrodecreased 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.

Details

Language :
English
ISSN :
13596535
Volume :
17
Issue :
1
Database :
Supplemental Index
Journal :
Antiviral Therapy
Publication Type :
Periodical
Accession number :
ejs57467210
Full Text :
https://doi.org/10.3851/IMP1940