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.

Conflict of interest statement

Potential conflict of interest: Dr. Peters recieved grants from Gilead. Dr. Andersen is a consultant for Tibotec. Dr. Pollard advises for Idenix. He is a consultant for Pfizer. He is on the Speakers' Bureau for Bristol Myers Squibb and Gilead. He is also a consultant for and is on the Speakers' Bureau for Boehringer Ingelheim. Dr. Rooney is an employee of and owns stocks in Gilead. He also owns stock in GlaxoSmithKline. Dr. Sherman is on the Speakers' Bureau and received grants from Roche and Schering. He is a consultant for and received grants from SciClone. He also advises for BMS. Dr. Swindells recieved grants from Bristol Myers, Novartis and Pfizer.

Figures

Fig. 1

Change in HBV DNA log10 levels from baseline over 48 weeks by treatment arm (mean and 99% CI error bars). The ADV and TDF arms were very similar over the first several sampling points, but there was a greater decrease in HBV DNA in the TDF arm over time.