title: Randomized controlled study of tenofovir and adefovir in chronic hepatitis B virus and HIV infection: ACTG A5127.
abstract: Chronic hepatitis B virus (HBV) infection is an important cause of morbidity and mortality in subjects coinfected with HIV. Tenofovir disoproxil fumarate (TDF) and adefovir dipivoxil (ADV) are licensed for the treatment of HIV-1 and HBV infection, respectively, but both have in vivo and in vitro activity against HBV. This study evaluated the anti-HBV activity of TDF compared to ADV in HIV/HBV-coinfected subjects. ACTG A5127 was a prospective randomized, double-blind, placebo-controlled trial of daily 10 mg of ADV versus 300 mg of TDF in subjects with HBV and HIV coinfection on stable ART, with serum HBV DNA >/= 100,000 copies/mL, and plasma HIV-1 RNA </= 10,000 copies/mL. This study closed early based on results of a prespecified interim review, as the primary noninferiority end point had been met without safety issues. Fifty-two subjects were randomized. At baseline, 73% of subjects had a plasma HIV-1 RNA < 50 copies/mL, 86% were HBeAg positive, 94% were 3TC resistant, median serum ALT was 52 IU/L, and 98% had compensated liver disease. The mean time-weighted average change in serum HBV DNA from baseline to week 48 (DAVG(48)) was -4.44 log(10) copies/mL for TDF and -3.21 log(10) copies/mL for ADV. There was no difference in toxicity between the 2 treatment arms, with 11 subjects (5 ADV and 6 TDF) experiencing elevations of serum ALT on treatment. In conclusion, over 48 weeks, treatment with either ADV or TDF resulted in clinically important suppression of serum HBV DNA. Both drugs are safe and efficacious for patients coinfected with HBV and HIV.
authors.affiliation: University of California, San Francisco, San Francisco, CA, USA. marion.peters@ucsf.edu
authors.forename: Marion G
authors.initials: MG
authors.lastname: Peters
authors.forename: Janet
authors.initials: J
authors.lastname: Andersen
authors.forename: Patrick
authors.initials: P
authors.lastname: Lynch
authors.forename: Tun
authors.initials: T
authors.lastname: Liu
authors.forename: Beverly
authors.initials: B
authors.lastname: Alston-Smith
authors.forename: Carol L
authors.initials: CL
authors.lastname: Brosgart
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Johnson
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: James F
authors.initials: JF
authors.lastname: Rooney
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.forename: Susan
authors.initials: S
authors.lastname: Swindells
authors.forename: Bruce
authors.initials: B
authors.lastname: Polsky
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1; D019694:Hepatitis B, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D000068698:Tenofovir; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil