title: Comparison of HBV-active HAART regimens in an HIV-HBV multinational cohort: outcomes through 144 weeks.
abstract: OBJECTIVE
  To explore factors associated with short and long-term hepatitis B virus (HBV) DNA suppression in a multinational cohort of HIV-HBV co-infected patients receiving HBV-active antiretrovirals.
  
  
  METHODS
  One hundred and fifteen HIV-HBV co-infected patients participating in one of the two global randomized clinical trials conducted by the Adult AIDS Clinical Trials Group of different antiretroviral regimens received either HBV monotherapy with either lamivudine or emtricitabine (N = 56), or HBV dual therapy with tenofovir disoproxil fumarate (TDF) + lamivudine or emtricitabine (N = 59). Associations of pretreatment characteristics with the primary (HBV DNA <200 IU/ml at 24 weeks) and longitudinal outcomes through 144 weeks were explored using logistic regression. HBV drug-resistance mutations were determined by pol sequencing in those with viral rebound.
  
  
  RESULTS
  The proportion with HBV DNA below 200 IU/ml was 60% (95% confidence interval 50-69%) at 24 weeks and 79% (95% confidence interval 69-88%) at 144 weeks. Pretreatment factors associated with the primary outcome were HBV DNA, CD4 T-cell count, and aspartate aminotransferase, but only pretreatment HBV DNA remained associated with long-term suppression (P < 0.0001). HBV therapy group was not significantly associated with the primary outcome at 24 weeks; however, longitudinally, a greater proportion in the dual-therapy group achieved HBV DNA below 200 IU/ml (P = 0.007). A higher proportion of hepatitis B e antigen-negative patients (n = 57) achieved HBV DNA below 200 IU/ml at any point, regardless of the therapy group. All 12 patients with emergence of lamivudine-resistant mutants were in the monotherapy group.
  
  
  CONCLUSIONS
  TDF-based dual HBV-active antiretroviral therapy is preferred to treat HIV-HBV co-infected patients. In resource-limited settings in which TDF may not be universally available, lamivudine or emtricitabine HBV monotherapy is a reasonable option in patients with low HBV replication.
authors.affiliation: aJohns Hopkins University, Baltimore, Maryland bHarvard School of Public Health, Boston, Massachusetts, USA cYRG Centre for AIDS Research and Education, Voluntary Health Services Hospital Campus, Taramani, Chennai dNational AIDS Research Institute-ICMR, Pune, India eUniversity of Zimbabwe Clinical Research Centre, College of Health Sciences, Harare, Zimbabwe fCollege of Medicine, Johns Hopkins Research Project, Department of Medicine, Blantyre, Malawi gNelson R Mandela School of Medicine, University of KwaZulu-Natal, Glenwood, South Africa hUniversity of Colorado School of Medicine, Aurora, Colorado iBrigham and Women's Hospital, Boston, Massachusetts jUCLA David Geffen School of Medicine, Los Angeles, California, USA.
authors.forename: Chloe L
authors.initials: CL
authors.lastname: Thio
authors.forename: Laura
authors.initials: L
authors.lastname: Smeaton
authors.forename: Kimberly
authors.initials: K
authors.lastname: Hollabaugh
authors.forename: Melissa
authors.initials: M
authors.lastname: Saulynas
authors.forename: Hyon
authors.initials: H
authors.lastname: Hwang
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Saravanan
authors.forename: Smita
authors.initials: S
authors.lastname: Kulkarni
authors.forename: James
authors.initials: J
authors.lastname: Hakim
authors.forename: Mulinda
authors.initials: M
authors.lastname: Nyirenda
authors.forename: Hussain Syed
authors.initials: HS
authors.lastname: Iqbal
authors.forename: Umesh G
authors.initials: UG
authors.lastname: Lalloo
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Campbell
authors.forename: Shahin
authors.initials: S
authors.lastname: Lockman
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents