title: Impact of lamivudine on HIV and hepatitis B virus-related outcomes in HIV/hepatitis B virus individuals in a randomized clinical trial of antiretroviral therapy in southern Africa.
abstract: OBJECTIVE
  To examine HIV and hepatitis B virus (HBV)-related outcomes in HIV/HBV-coinfected participants in the PHIDISA II study by use of HBV-active vs. non-HBV-active antiretroviral therapy (ART).
  
  
  METHODS
  PHIDISA II was a randomized study of ART therapy in HIV-infected adults employing zidovudine along with didanosine, or lamivudine along with stavudine in a factorial 2x2 design. HIV/HBV-coinfected participants by randomization received HBV-active or non-HBV-active ART. The following outcomes of interest were examined: immunological recovery and HIV RNA suppression; hepatic flare; HBV DNA suppression; and mortality.
  
  
  RESULTS
  HIV/HBV coinfection was present in 106 of 1771 (6%) of participants. Participants with HIV/HBV coinfection were more likely to be men, and have higher baseline alanine aminotransferase, lower albumin, and lower platelets than those with HIV monoinfection. Median CD4 cell gain and HIV RNA suppression was similar across all groups. Hepatic flare was observed in 9.4% of coinfected and 0.02% monoinfected participants. HBV DNA suppression (<55 IU/ml) at week 48 was observed in only 33% of those on lamivudine vs. 13% in those on no HBV-active drugs (P = 0.13). Mortality over follow-up was significantly greater in coinfected (17%) than monoinfected (11%) participants (P = 0.04).
  
  
  CONCLUSIONS
  In summary, the use of lamivudine-containing ART in HIV/HBV participants in PHIDISA II resulted in little additional benefit over that of ART itself and failed to impact on the greater mortality in this group. These data provide strong support for recent guidelines advocating the use of tenofovir in all HIV-HBV-coinfected individuals initiating ART.
authors.affiliation: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. gmatthews@kirby.unsw.edu.au
authors.forename: Gail V
authors.initials: GV
authors.lastname: Matthews
authors.forename: Prince
authors.initials: P
authors.lastname: Manzini
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Hu
authors.forename: Paul
authors.initials: P
authors.lastname: Khabo
authors.forename: Patrick
authors.initials: P
authors.lastname: Maja
authors.forename: Gugu
authors.initials: G
authors.lastname: Matchaba
authors.forename: Phumele
authors.initials: P
authors.lastname: Sangweni
authors.forename: Julie
authors.initials: J
authors.lastname: Metcalf
authors.forename: Nicholaas
authors.initials: N
authors.lastname: Pool
authors.forename: Susan
authors.initials: S
authors.lastname: Orsega
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D000328:Adult; D000353:Africa, Southern; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D015497:HIV-1 / Q000187:drug effects*; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018119:Stavudine / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents; D019259:Lamivudine; D018119:Stavudine; D016049:Didanosine