title: A randomized trial of combination hepatitis B therapy in HIV/HBV coinfected antiretroviral naïve individuals in Thailand.
abstract: Coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) is associated with considerable liver disease morbidity and mortality. Emerging HIV epidemics in areas of high HBV endemicity such as Asia are expanding the population with HIV/HBV coinfection. Limited randomized trial data exist to support current guidelines for HBV combination therapy in HIV/HBV coinfection. The objective of this prospective randomized clinical trial was to compare the strategy of HBV monotherapy with lamivudine (LAM) or tenofovir disoproxil fumarate (TDF) versus HBV combination therapy with LAM/TDF in antiretroviral-naïve HIV/HBV-coinfected subjects in Thailand. Thirty-six HIV/HBV-coinfected subjects initiating highly active antiretroviral therapy (HAART) were randomized to either LAM (arm 1), TDF (arm 2), or LAM/TDF (arm 3) as HBV-active drugs within HAART. At week 48, time-weighted area under the curve analysis revealed that the median HBV DNA reduction from baseline was 4.07 log(10) c/mL in arm 1, 4.57 log(10) c/mL in arm 2, and 4.73 log(10) c/mL in arm 3 (P = 0.70). HBV DNA suppressed to <3 log(10) c/mL in 46% in arm 1, 92% in arm 2, and 91% in arm 3 (P = 0.013, intent-to-treat analysis). HBV-resistant changes were detected in two subjects, both in arm 1. Hepatitis B e antigen (HBeAg) loss was observed in 33% of HBeAg-positive subjects, and 8% experienced hepatitis B surface antigen loss. Hepatic flare was observed in 25% of subjects.
  
  
  CONCLUSIONS
  LAM monotherapy resulted in a greater proportion of subjects with HBV DNA >3 log(10) c/mL at week 48 and in early resistance development. This study confirms current treatment guidelines that recommend a TDF-based regimen as the treatment of choice for HIV/HBV coinfection, but does not demonstrate any advantage of HBV combination therapy in this short-term setting.
authors.affiliation: Viral Hepatitis Program, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Darlinghurst, Sydney, NSW, Australia. gmatthews@nchecr.unsw.edu.au
authors.forename: Gail V
authors.initials: GV
authors.lastname: Matthews
authors.forename: Anchalee
authors.initials: A
authors.lastname: Avihingsanon
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: Rungsun
authors.initials: R
authors.lastname: Rerknimitr
authors.forename: Panusit
authors.initials: P
authors.lastname: Petcharapirat
authors.forename: Pip
authors.initials: P
authors.lastname: Marks
authors.forename: Joe
authors.initials: J
authors.lastname: Sasadeusz
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Scott
authors.initials: S
authors.lastname: Bowden
authors.forename: Stephen
authors.initials: S
authors.lastname: Locarnini
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000627:therapeutic use*; D003521:Cyclopropanes; D004279:DNA, Viral / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D011446:Prospective Studies; D000068698:Tenofovir; D013785:Thailand; D016896:Treatment Outcome; D015215:Zidovudine / Q000627:therapeutic use*
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; D015215:Zidovudine; D000068698:Tenofovir; D000225:Adenine; C098320:efavirenz