title: Long-term outcome of primary non-responders to tenofovir therapy in HIV/HBV-co-infected patients: impact of HBV genotype G.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service d'Hépatologie and INSERM U773 CRB3, AP-HP Hôpital Beaujon, Clichy, France. olivier.lada@inserm.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Lada
authors.forename: Anne
authors.initials: A
authors.lastname: Gervais
authors.forename: Michel
authors.initials: M
authors.lastname: Branger
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Benedicte
authors.initials: B
authors.lastname: Roquebert
authors.forename: Gilles
authors.initials: G
authors.lastname: Collin
authors.forename: Gil
authors.initials: G
authors.lastname: Fraqueiro
authors.forename: Rami
authors.initials: R
authors.lastname: Moucari
authors.forename: Gwen
authors.initials: G
authors.lastname: Hamet
authors.forename: Michelle
authors.initials: M
authors.lastname: Martinot-Peignoux
authors.forename: Sophie
authors.initials: S
authors.lastname: Matheron
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D060085:Coinfection / Q000188:drug therapy; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D005838:Genotype; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy*; D006509:Hepatitis B / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D012189:Retrospective Studies; D000068698:Tenofovir; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D063065:Organophosphonates; D003841:Deoxycytidine; D019259:Lamivudine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine