title: Patterns and causes of suboptimal response to tenofovir-based therapy in individuals coinfected with HIV and hepatitis B virus.
abstract: BACKGROUND
  Tenofovir (TDF) is effective for treatment of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) infection; however, some individuals have ongoing HBV viremia, the reasons for which are unclear. We determined the patterns and factors associated with detectable HBV DNA in HIV-HBV-coinfected subjects on highly active antiretroviral therapy (HAART).
  
  
  METHODS
  One hundred sixty-five HIV-HBV-coinfected individuals from the United States, Australia, and Thailand, the majority of whom were on HAART at study entry, were prospectively followed semiannually for a median of 2.8 years. Logistic regression was used to determine factors associated with detectable HBV DNA.
  
  
  RESULTS
  Anti-HBV regimens were TDF/emtricitabine (57%), lamivudine or emtricitabine (19%), or TDF monotherapy (13%). During follow-up, HBV DNA was detected at 21% of study visits and was independently associated with hepatitis B e antigen (HBeAg), HAART <2 years, CD4 <200 cells/mm(3), detectable HIV RNA, reporting <95% adherence, and anti-HBV regimen. TDF/emtricitabine was less likely to be associated with detectable HBV than other regimens, including TDF monotherapy (odds ratio, 2.79; P = .02). In subjects on optimal anti-HBV therapy (TDF/emtricitabine) and with undetectable HIV RNA, HBeAg, CD4 <200 mm(3), and reporting <95% adherence remained associated with detectable HBV DNA. Three main patterns of HBV viremia were observed: persistent HBV viremia, viral rebound (>1 log from nadir), and viral blips. No TDF resistance was identified.
  
  
  CONCLUSIONS
  Tenofovir/emtricitabine was superior to other anti-HBV regimens in long-term HBV suppression. HBV viremia on therapy was identified in 1 of 3 main patterns. Suboptimal adherence was associated with detectable HBV DNA during therapy, even when HIV was undetectable.
authors: The Kirby Institute, University of New South Wales, Sydney, NSW 2010, Australia. gmatthews@kirby.unsw.edu.au
authors: Gail V
authors: GV
authors: Matthews
authors: Eric C
authors: EC
authors: Seaberg
authors: Anchalee
authors: A
authors: Avihingsanon
authors: Scott
authors: S
authors: Bowden
authors: Gregory J
authors: GJ
authors: Dore
authors: Sharon R
authors: SR
authors: Lewin
authors: Joe
authors: J
authors: Sasadeusz
authors: Peter A
authors: PA
authors: Revill
authors: Margaret
authors: M
authors: Littlejohn
authors: Jennifer F
authors: JF
authors: Hoy
authors: Robert
authors: R
authors: Finlayson
authors: Kiat
authors: K
authors: Ruxrungtham
authors: Melissa
authors: M
authors: Saulynas
authors: Stephen
authors: S
authors: Locarnini
authors: Chloe L
authors: CL
authors: Thio
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D000998:Antiviral Agents / Q000008:administration & dosage*; D001315:Australia; D060085:Coinfection / Q000188:drug therapy*; D004279:DNA, Viral / Q000097:blood; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068679:Emtricitabine; 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; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage*; D000068698:Tenofovir; D013785:Thailand; D017211:Treatment Failure; D014481:United States
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine