title: Virological Response to Tenofovir Disoproxil Fumarate in HIV-Positive Patients with Lamivudine-Resistant Hepatitis B Virus Coinfection in an Area Hyperendemic for Hepatitis B Virus Infection.
abstract: BACKGROUND
  Sequential addition of tenofovir disoproxil fumarate (TDF) is often needed for patients coinfected with HIV and hepatitis B virus (HBV) who develop HBV resistance to lamivudine after combination antiretroviral therapy (cART) containing only lamivudine for HBV. We aimed to assess the virological response of HBV to add-on TDF in patients coinfected with lamivudine-resistant HBV.
  
  
  METHODS
  Between November 2010 and December 2014, 33 HIV/HBV-coinfected patients with lamivudine-resistant HBV and 56 with lamivudine-susceptible HBV were prospectively included. TDF plus lamivudine was used to substitute zidovudine or abacavir plus lamivudine contained in cART in patients with lamivudine-resistant HBV infection, while patients with lamivudine-susceptible HBV infection received TDF plus lamivudine as backbone of cART. Serial determinations of plasma HBV DNA load, HBV serologic markers, and liver and renal functions were performed after initiation of TDF-containing cART.
  
  
  RESULTS
  Of 89 patients included, 38.6% tested positive for HBV envelope antigen (HBeAg) at baseline. The plasma HBV DNA level at enrollment of lamivudine-resistant and lamivudine-susceptible group were 6.1 ± 2.2 log10 and 6.0 ± 2.2 log10 copies/mL, respectively (p = 0.895). The cumulative percentage of HBV viral suppression in lamivudine-resistant and lamivudine-susceptible group was 81.8% and 91.1% at 48 weeks, respectively (p = 0.317), which increased to 86.7% and 96.2% at 96 weeks, respectively (p = 0.185). At 48 weeks, 11 patients testing HBeAg-positive at baseline failed to achieve viral suppression. In multivariate analysis, the only factor associated with failure to achieve viral suppression at 48 weeks was higher HBV DNA load at baseline (odds ratio, per 1-log10 copies/mL increase, 1.861; 95% CI, 1.204-2.878). At 48 weeks, HBeAg seroconversion was observed in 5 patients (1 in the lamivudine-resistant group and 4 in the lamivudine-susceptible group; p = 0.166). During the study period, HBsAg levels decreased over time, regardless of lamivudine resistance. Loss of HBsAg was observed in 3 (3.4%) patients in the lamivudine-susceptible group.
  
  
  CONCLUSIONS
  Add-on TDF-containing cART in patients coinfected with lamivudine-resistant HBV achieved a similar rate of HBV viral suppression compared to TDF-containing cART as initial regimen in patients coinfected with lamivudine-susceptible HBV. A higher baseline HBV DNA load and HBeAg positivity were associated with failure to achieve HBV viral suppression.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sui-Yuan
authors.initials: SY
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wang-Huei
authors.initials: WH
authors.lastname: Sheng
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Hsin-Yun
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
authors.forename: Kuan-Yeh
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Chuang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Su
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.|China Medical University, Taichung, Taiwan.
authors.forename: Chien-Ching
authors.initials: CC
authors.lastname: Hung
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Shan-Chwen
authors.initials: SC
authors.lastname: Chang
mesh_terms: D000328:Adult; D060085:Coinfection / Q000150:complications / Q000453:epidemiology; D004338:Drug Combinations; D024882:Drug Resistance, Viral / Q000187:drug effects; D019353:Endemic Diseases; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006509:Hepatitis B / Q000150:complications / Q000453:epidemiology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D000068698:Tenofovir / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D019259:Lamivudine; D000068698:Tenofovir